SUMMER 2005

FSHA publication of the FacioscapulohumeralW Muscular Dystrophyatch Society

Index FSH Society Facilitates Myostatin Inhibitor Research Myostatin Research ...... Front Cover, 4, 5 By Daniel Paul Perez President’s Letter ...... 2, 3 Guide to Acronyms ...... 3 I want to illustrate how the FSH Soci- the studies with which she was involved. National Websites ...... 4 ety works, which attests to our unique I recommended that Dr. Whittemore In Memoriam: Karen Johnsen ...... 5 ability and networking efforts on behalf of talk with Dr. Tawil, who serves on the FSH Karen’s Dream for a Cure ...... 5, 6 FSHD. This story highlights our Her- Society’s Scientific Advisory Board and has In Memoriam: William T. Michael ...... 6 culean efforts to move FSHD into the done clinical trials on FSHD. He also is a Younger Research Grant ...... 6 Gala Benefit ...... 7-10 member of the multi-center Muscle Study mainstream for research. After years of FSH Society Funded Grants ...... 11-15 neglect in FSHD research, the FSH Soci- Group (MSG) that is exclusively designed FSH Society Grant Application Process . .15 ety has made great strides behind the and structured to do clinical trials on mus- First FSH Society Roberts Grant . . . . .16, 17 scenes. Much of the work that we do is cle disease. Additionally, Dr. Tawil runs Second FSH Society Roberts Grant . . . . .16 confidential. However, when the work the NIH FSHD National Registry (see 2005 Bronfman Grant ...... 17 results in this kind of study, it is time for article, page 36) at the University of 10th Bronfman Fellowship ...... 17 7th & 8th Delta Railroad Grant ...... 17 Rochester. us to blow our own horn and let you Tides Foundation Grant ...... 17 know what our organization, with your On March 11, 2003, Dr. Kathryn Wag- MDCRC Fellowships Available ...... 18 support, is ner, M.D., Ph.D., NY Community Trust Grant ...... 18 accomplishing There have been very few clinical trials in FSHD a neurologist and NIH Program Announcements ...... 18-20 every day. Since and [we have] helped Dr. Wagner position her researcher at Congressional Testimony ...... 20-23 the Society does Johns Hopkins CRCs Open ...... 23 Funding Arrays ...... 24-27 work on myostatin inhibition at Johns Hopkins Hospital in Balti- not have a pub- Tracking MD Funding ...... 24 lic relations and with the pharmaceutical industry which repre- more, requested NHGRI Funding ...... 24-26 marketing team, sents, for the first time since the discovery of my assistance. Dr. History of the MD-CARE Act ...... 28-30 this is our Wagner was col- What is CRISP? ...... 30 FSHD in 1886, a serious candidate therapy to opportunity to laborating with Combined Federal Campaign ...... 30 credit ourselves treat, ameliorate and reverse the effects of FSHD! Se-Jin Lee who Porter Named NIH MD Director . . . .30, 31 discovered and NIH MD Program Staff ...... 31 where credit is Albuterol Trial Stalled ...... 31-33 due. This is the real story behind the has done much of the subsequent work on van der Maarel & Frantz Article ...... 32 myostatin-inhibitor trials and the years myostatin, an inhibitor of muscle growth. First FSHD Medical Textbook ...... 33, 34 invested into seeing it come to pass. Their work appeared in the December Chromatin Structure ...... 34 In the autumn of 2001, Lisa-Anne 2002 issue of “Annals of Neurology” on Toronto FSHD IRC Workshop ...... 34, 35 Whittemore, Ph.D., from the Wyeth the effects of inhibiting myostastin in a National DM & FSHD Registry ...... 36 mouse model of muscular dystrophy. Respiratory & Breathing Issues ...... 36 Ayerst Genetics Institute in Cambridge, Non-affected Family Members ...... 36 MA became a professional member of the Dr. Wagner wanted to talk with the Early Onset FSHD & IFSHD ...... 37 FSH Society. I contacted her to see if the Society about applying this method to Pregnancy & Delivery Study ...... 37 FSH Society could be of further assistance, FSHD. I, of course, wrote a lengthy Brain & Tissue Banks ...... 37 and to inquire about her areas of interest. response outlining why FSHD would be an Prenatal Genetic Testing in US ...... 38 At that time, Dr. Whittemore had ques- excellent candidate. Around this time, Dr. Mission Statement of Society ...... 38 Tawil said he and his colleagues at the Making a Bequest ...... 39 tions regarding muscle satellite pool cell Bulletin Board & Chat ...... 39 exhaustion in FSHD and the current state MSG were interested in myostatin- Society Welcomes LaPlante ...... 39 of clinical trials on FSHD. We referred her inhibitor research. I had Drs. Wagner and First Hand: Aubrie Lee ...... 39, 40 to the top three researchers in molecular Tawil contact one another. First Hand: Justin Cohen ...... 40 genetics and cell biology: Drs. Winokur, Dr. Wagner asked if we could provide Dardonville Raises Funds ...... 40 Figlewicz and Frants. Also, we referred the number of FSHD patients within one End of Tax Season Bar Crawl ...... 40 hour driving distance of Johns Hopkins. The Third Choice ...... 41, 42 her to the top clinicians in research trials: Scooting Across the Sea ...... 42 Drs. Tawil, Kissel and van der Kooi. I Thanks to Karen Johnsen and her Mid- Visit us @ www.fshsociety.org ...... 43 indicated the senior people who work Atlantic Support Group, as well as Carol Read-a-Thon in MD ...... 43 with Tawil, Kissel and van der Kooi as Perez with the national list of FSHD Memorial Weekend Garage Sale ...... 43 Drs. Griggs, Mendell and Padberg. Due to patients, within 24 hours, we were able to Acknowledgements ...... 43-47 the confidential nature of her work, Dr. provide the total number of affected Adapted Van For Sale ...... 43 FSHD patients listed with the Society, not- Thank You! ...... 47 Whittemore asked that we not disclose FSH Society Fact Sheet ...... 47 her name to FSHD researchers regarding continued on page 4 Membership Application/Donation . . . . .48 2 FSH WATCH NEWSLETTER SUMMER 2005

Board of Directors Letter from the President Stephen J. Jacobsen, Ph.D., Chairman Choosing & Maintaining Direction in the Face of Gain & Loss Daniel P. Perez, President & CEO William R. Lewis, M.D., Vice-Chairman By Daniel Paul Perez, President and CEO, FSH Society, Inc. Richard A. Lefebvre, M.B.A., FHFMA, Dear Reader & Friend of the FSH Society, over the past eight years speaks brilliantly Secretary There has been remarkable progress in for itself. William Michael, C.P.A., Treasurer the past few years! The FSH Society is More countries are joining the E. Ann Biggs-Williams growing and becoming even more produc- fight against FSHD – foreign funding Howard L. Chabner, J.D. tive thanks to you who have, throughout agencies, volunteer health organizations, William E. Hall Jr., J.D.* the years, been generous and forthcoming patient support and network groups are Louis M. Kunkel, Ph.D. with much needed help. organizing. C. Larry Laurello, P.E. In the past year, we have lost more During this past season, we sub- William R. Lewis III, M.D. than our fair share of dear friends, family mitted testimonies before the U.S. Con- Theodore L. Munsat, M.D.* members and loved ones. Balancing these gress regarding the need for projects and Paul Schultz, M.D. * losses are the gains we have made in funding on FSHD (see pages 20-23). Robert F. Smith, J.D. FSHD research and community building. The Society continues to work Z. John Stekly, Sc.D. These are our accomplishments in 2004 closely with the NIH, a federal research through to the present: agency responsible for muscular dystrophy Scientific Advisory Board A promising new drug trial is being research. FSHD research programs are David E. Housman, Ph.D., Chair conducted with FSHD patients using slow in coming but the foundation for the Michael R. Altherr, Ph.D. Wyeth-Ayerst myostatin-inhibitor MYO- research programs through the NIH is Robert H. Brown Jr., M.D./D.Phil.* 029 (See front cover). secure. Rune Frants, Ph.D. A study on pregnancy and preg- The FSH Society represented by Robert C. Griggs, M.D. nancy outcomes in FSHD was initiated myself and our legal counsel, Morgan Stephen J. Jacobsen, Ph.D. and exclusively funded by the Society (see Downey, changed the complexion of U.S. Louis M. Kunkel, Ph.D. page 37). muscular dystrophy research forever by re- William R. Lewis, M.D. A study was initiated by the Society writing the MD-CARE Act 2001 to William R. Lewis III, M.D. on defining infantile and early onset include all dystrophies and not just DMD. George W. A. M. Padberg, M.D. FSHD (see page 37). Muscular dystrophy research is now get- Rabi Tawil, M.D. The Society is initiating a study on ting its long overdue and needed federal breathing and respiratory issues in FSHD funding. Though FSHD still has a long * Board Member Emeritus (see page 36). way to go, our concerns are being heard Cutting edge research, clinical about the disproportionate funding within General Counsel projects and fellowships continue to push the nine dystrophies (see pages 28-30 for Morgan Downey the envelop establishing new ground for History of the MD CARE Act). Suite 300, 1250 24th St. N.W. high risk and new innovative research I continue to serve on the U.S. Washington, D.C. 20037 directions for FSHD (see pages 11-15). federal government MD-CARE Act 2001 (202) 466-0580 We have invested more than $1.2 million Coordinating Committee to help oversee (202) 776-7712 Fax since the inception of the research pro- and devise the research and education gram in 1997. plan for all MD research. FSHD is promi- Executive Director We organize and co-chair the nently and well represented in the new Carol A. Perez, M.Ed. international consortium meeting of research plan for dystrophy (see pages 28- researchers to network and encourage col- 30, History). Boston Office laboration and the sharing of ideas and We disseminate valuable and Carol A. Perez materials (see pages 34-35 for Toronto). important information through all avail- FSH Society, Inc. We work with industry, research able means. 3 Westwood Road labs and national cell repositories and tis- We respond to requests for infor- Lexington, MA 02420 sue banks to foster research, clinical trials mation from researchers, doctors, agen- (781) 860-0501 and genetic testing (see pages 31-33, cies, FSHD families and patients (781) 860-0599 Fax Albuterol). worldwide. We lecture at graduate and [email protected] We successfully brought prenatal medical schools; we tell doctors we are testing for FSHD to the U.S. for the first here as a resource for them. San Diego Office time ever this year (see page 38). We continue to work with doctors Stephen J. Jacobsen Australian experts on IVF pre- and patients to develop national and local FSH Society, Inc. implantation genetic diagnosis (PGD) resources, programs and educational 1507 Traske Road prenatal testing for FSHD were brought material. Encinitas, CA 92024 to the U.S. to share their experience in The FSH Society website (760) 632-5411 IVF PGD for FSHD. (www.fshsociety.org), international bul- [email protected] We continue to recruit, identify letin board and chat room continue as a and fund researchers to work on specific unique and primary resource for those questions that the FSH Society Scientific needing advice and support from others E-mail: [email protected] Advisory Board wishes to see addressed. coping with FSHD. Website: http://www.fshsociety.org The FSHD research publication record continued on page 3 FSH WATCH NEWSLETTER SUMMER 2005 3

Direction, continued from page 2 A Guide to Acronyms In the interest of readability and space, we would like to offer a list of acronyms for your reference. The FSH Society remains the We will use these acronyms throughout the newsletter. watchdog and guardian for FSHD research AAN American Academy of Neurology world wide by aggressively promoting AAV Adeno-associated viral research projects and treatments through AFM Association Française Contre les Myopathies advocacy, networking, and collaboration AFO Ankle Foot Orthotic with patients/families, researchers, doctors AHRQ Agency for Health Care Research and Quality and funding agencies. ASHG American Society for Human Genetics We need you! We need you to con- BMD Becker Muscular Dystrophy tribute to the FSH Society now. We need CDC Centers for Disease Control and Prevention you to raise funds for the FSH Society now. CFC Combined Federal Campaign There are many ways to accomplish this as CIHR Canadian Institutes of Health Research you can see in this newsletter. We need CIHR IG Canadian Institutes of Health Research - Institute of Genetics you to volunteer to participate in studies. CRISP NIH Computer Retrieval of Information on Scientific Projects We need you to register with the NIH CSR DHHS NIH Center for Scientific Review FSHD registry (see page 36). We need you DHHS Department of Health and Human Services to work with us. We need you! DM Myotonic Muscular Dystrophy Oliver Wendell Holmes, Jr., wrote: “it DMD Duchenne Muscular Dystrophy [is] not so much where we stand as in DoD Department of Defense what direction we are moving; To reach DOE Department of Education the port of heaven, we must sail sometimes EDMD Emery-Dreifuss MD with the wind and sometimes against it - FDA Food and Drug Administration FSHD Facioscapulohumeral Muscular Dystrophy but we must sail, and not drift, nor lie at HIBM Hereditary Inclusion Body Myopathy anchor.” HRSA Health Resources and Services Administration The past few years have brought signif- IFSHD Infantile Facioscapulohumeral Muscular Dystrophy icant gains as you can see. At the same IOM Institute of Medicine time, many near and dear to us in the IRC International Research Consortium Society have lost their battle with FSHD – LGMD Limb Girdle Muscular Dystrophy Karen Johnsen, Lady Hall, Joseph Grech, MD Muscular Dystrophy and William “Billy” Michael, to name a MD-CARE Muscular Dystrophy Community Assistance, Research and Education few. We will maintain our direction and MDA-USA Muscular Dystrophy Association United States of America movement towards a solution, understand- MDC Muscular Dystrophy Canada ing, treatment or a cure for FSHD. MDCC Muscular Dystrophy Coordinating Committee Your dollars are working hard toward a MDCRC Muscular Dystrophy Cooperative Research Centers goal we know we can achieve. The Society MDRTF Muscular Dystrophy Research Task Force is making bold progress researching the MDRWG Muscular Dystrophy Research Working Group causes of FSHD. You should also know MYO-29 Myostatin-inhibitor that here at the FSH Society we watch NCRR DHHS NIH National Center for Research Resources every single hard-won penny. Our offices NHGRI DHHS NIH National Human Genome Research Institute are modest. Our staff is very small. Our NHLBI DHHS NIH National Heart, Lung, and Blood Institute own involvement, together with that of NIAMS DHHS NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases other friends who have contributed effort NICHD DHHS NIH National Institute of Child Health and Human Development and time, add up to the equivalent of tens NIH DHHS National Institutes of Health NINDS DHHS NIH National Institute of Neurological Disorders and Stroke of thousands more dollars. Nothing is NRSA National Research Service Awards wasted! OASH Office of Assistant Secretary of Health Please send your contribution today. OCPL DHHS NIH Office of Communication and Public Liaison We have inserted a self-addressed return OD DHHS NIH Office of the Director envelope in this newsletter for your con- ODS DHHS NIH Office of Dietary Supplements venience. We now have the capacity to OPM Office of Personnel Management accept credit card donations. OPMD Oculopharyngeal MD Thank you in advance for your gen- ORD Office of Rare Diseases erosity and for taking a important moment PPDMD/PPMD Parent Project Duchenne Muscular Dystrophy to help solve FSHD. PT Physical Therapy SAMHSA Substance Abuse and Mental Health Services The FSH Watch is published by the FSH Society and distributed by mail to its members and support- ers. All material is copyrighted and may not be reproduced without written permission. To be It is the editorial policy to report on develop- placed on the mailing list or to submit an article please write to: Carol Perez, FSH Society, 3 West- ments regarding FacioScapuloHumeral wood Road, Lexington, MA 02420 USA. Articles may be edited for space and clarity. Every effort Muscular Dystrophy (FSHD), but not to has been made to ensure accuracy in the newsletter. If you wish to correct an error, please write to endorse any of the drugs or treatments dis- the above address. Look for us on the internet at: www.fshsociety.org cussed. We urge you to consult with your own Editors: Daniel Paul Perez, Carol Perez, Susan L. Stewart; Editorial Assistance: Howard L. physician about the procedures mentioned. Chabner, Stephen J. Jacobsen, Elly Merkle, Perrin LaPlante & Charles C. Perez 4 FSH WATCH NEWSLETTER SUMMER 2005

Myostatin Inhibitor Research, continued from front page ing de novo cases and information on a defect in the myostatin blockade [“Myo- safety trial is to study MYO-029 in adult functional limitations. All of this informa- statin Mutation Associated with Gross patients with muscular dystrophy. Condi- tion was given without violating confiden- Muscle Hypertrophy in a Child,” Markus tion Treatment or Intervention Phase.” For tiality, as it was given in numbers, not Schuelke, M.D., Kathryn R. Wagner, M.D., diseases: Becker Muscular Dystrophy, names. Dr. Wagner had not been able to Ph.D., Leslie E. Stolz, Ph.D., Christoph Facioscapulohumeral Muscular Dystrophy, get this information from the MDA. Hübner, M.D., Thomas Riebel, M.D., Limb-Girdle Muscular Dystrophy. Drug: Dr. Wagner’s next request was for pho- Wolfgang Kömen, M.D., Thomas Braun, MYO-029. Study Type: Interventional. tographs of FSHD patients for her to pres- M.D., Ph.D., James F. Tobin, Ph.D., and Study Design: Treatment, Safety Study. ent to Wyeth. We sent out a message on Se-Jin Lee, M.D., Ph.D., NEJM, Volume Ages Eligible for Study: 18 years and the bulletin board asking for such photos 350:2682-2688, No. 26]. The article gen- above and both genders eligible for study. and your response was overwhelming! As erated much excitement in the main- Inclusion criteria are: written informed Dr. Wagner commented, “I wanted to take stream media and among dystrophy consent, confirmed clinical and molecular a moment away from working on my sufferers and their families. diagnosis, and, independently ambulatory. ‘pitch’ to Wyeth to let you know how won- There have been very few clinical trials The exclusion criteria are: certain clinical derful I think the pictures are. Together I in FSHD and our work together has conditions, use of steroids or other med- think they capture both the humanity of helped Dr. Wagner position her work on ications that affect muscle function, sensi- the people and the disabling qualities of myostatin inhibition at Johns Hopkins tivity to monoclonal antibodies or protein the disease. I hope I get a chance to meet with the pharmaceutical industry which pharmaceuticals, and pregnant or lactating some of these people. If you receive any represents, for the first time since the dis- women. more I will try to include them. I can't covery of FSHD in 1886, a serious candi- Location and Contact Information: imagine that anyone seeing them would date therapy to treat, ameliorate and Please refer to this study by not be moved as I am.” On June 26, 2003, reverse the effects of FSHD! The com- ClinicalTrials.gov Dr. Wagner made her presentation to mencement of this unique therapy and identifier NCT00104078 Wyeth on FSHD at a meeting which Dr. promising treatment is strongly attributa- District of Columbia Tawil attended. Her presentation was a ble to Dr. Wagner’s excellent clinical Research Site, Washington, District of smashing success. Wyeth slated FSHD as research work and her consummate profes- Columbia, 20010, U.S.; Recruiting the lead candidate for myostatin trials and sionalism in dealing with patients, pharma- Research Coordinator (202) 884-4110 designated future planning meetings for ceuticals, and clinical and research Kansas clinical trials protocol design. collaborators. Research collaborations with Research Site, Kansas City, Kansas, Dr. Wagner attended a FSH Society Drs. Whittemore, Tawil, Wyeth Pharma- U.S.; Recruiting Research Coordinator mid-Atlantic support group on Sunday, ceuticals, and the FSH Society all worked (913) 588-5095 May 23, 2004 at the home of Karen to bring this to fruition. Maryland Johnsen in Bowie, Maryland to educate Wyeth Ayerst has posted information Research Site, Baltimore, Maryland, patients on her work on myostatin- on its trial on the website 21287-7519, U.S.; Recruiting For Study inhibitor and the upcoming clinical trials. www.clinicaltrials.gov Information Call: (866) 879-7480 In June 2004, we were able to indicate The MYO-029 page for the Wyeth trial Massachusetts that, if all went well with early clinical is found at Research Site, Boston, Massachusetts, phases, Wyeth Pharmaceutical planned to http://www.clinicaltrials.gov/ct/ U.S.; Recruiting Research Coordinator conduct a clinical trial in inhibitor of myo- show/NCT00104078?order=2 (617) 525-6763 statin for FSHD, as well as for LGMD and The study is titled: “A Safety Study in Missouri Becker, beginning in the fall. The Society Adult Muscular Dystrophy Patients” and Research Site, St. Louis, Missouri, built a case for FSHD to be the lead can- researchers are currently recruiting U.S.; Recruiting Research Coordinator didate for this trial and succeeded. patients. Wyeth, who sponsors the trials (866) 879-7480 Also in June 2004, Dr. Wagner co- and provides the information states, “The New York authored a paper on a German boy having purpose of this phase I/II, multicenter, Research Site, Rochester, New York, U.S.; Recruiting Research Coordinator National Websites (585) 275-7680 National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Ohio http://www.niams.nih.gov/ Research Site, Columbus, Ohio, U.S.; National Institute of Neurological Disorders and Stroke (NINDS) Recruiting Research Coordinator http://www.ninds.nih.gov/ (614) 722-2203 National Institute of Child Health and Human Development (NICHD) Over the years, the Society has collect- http://www.nichd.nih.gov/ ed information on possible Wyeth-Ayerst National Heart, Lung, and Blood Institute (NHLBI) sites for myostatin inhibitor MYO-029 http://www.nhlbi.nih.gov/ clinical trial on FSHD. We want to get the Office of Dietary Supplements (ODS) http://dietary-supplements.info.nih.gov/ continued on page 5 FSH WATCH NEWSLETTER SUMMER 2005 5 In Memoriam Karen’s Dream for a Cure By Doris Olds Eck Karen Lynne Johnsen 1956-2004 Those of you who receive the FSH The FSH Society is deeply grieved to inform you of the death newsletter on a regular basis may remem- of our board member, Karen Lynne Johnsen, on December 14, ber the Fall 1999 article, “Ms. Wheelchair 2004, at age 48. In her lifetime, Karen accomplished many things Maryland, Inc. donates $5,000 for research while living with FSHD and the many physical problems imposed. to the FSH Society.” In this article, I Karen and her husband, Dean, formed a support group which reflected on my daughter, Karen Lynne they hosted since 1990 for people interested in FSHD. Karen’s Johnsen’s, life and the challenges she faced warmth and love touched the FSHD community worldwide. in dealing with FSHD. My beautiful angel, Karen was a role model and an excellent teacher. With Dean, Karen, died of respiratory failure as a result Karen gave support to the patients, caregivers and family mem- of this debilitating disease on December bers throughout the Mid-Atlantic region and, via internet, the 14th. She was only 48 years old. For those entire world. Karen died from respiratory complications as a result of the disease. We of you who did not know about Karen, I extend our deepest sympathy to her family and to her husband, Dean, and son, Jeremy. want to summarize some of the highlights We are particularly hopeful that Karen’s mother, Doris Olds Eck, will be successful in her campaign to raise research dollars for a cure, as she explains in the letter below. of her achievements and dedicated efforts to assist and support others with MD and other physical disabilities. Myostatin Inhibitor Research, continued from page 4 Born in Maryland, Karen received a word out to your family members with University, Columbus, Ohio (Jerry FSHD and to those you know who live Mendell); and University of Texas South- close to the clinical trial test sites to be western, Dallas, Texas (Gil Wolfe). sure that FSHD was well enrolled and sub- Several sites in the UK may be scribed. This is not a problem at the involved although we are not certain at moment; the other two dystrophies BMD this time: University of Newcastle upon and LGMD patients may take a bit longer Tyne, Newcastle upon Tyne, United King- to recruit. Please see dom (Kate Bushby); King's College Hospi- http://www.fshsociety.org/fsh/ tal, London, England (Michael Rose, MYO029SitesFSHD.html Caroline Murphy); and Oxford University, Karen Johnsen and friends for more detail on the trials. Oxford, United Kingdom (David Hilton- Based on information gathered to date Jones). degree in early childhood development each site will enroll 12 patients - four On December 19, 2004, Dr. Anthony and education from Prince George's Com- FSHD, four LGMD, and four Becker MD. Amato attended the New England FSHD munity College. She was director of There are some side effects consistent support group, facilitated by Carol Perez, Beltsville Agriculture Day Care; a retired with monoclonal antibody therapy. The in Wellesley, MA to educate patients on medical records clerk at the University of MSTN-inhibitor drug is administered via FSHD and his forthcoming work on myo- Maryland, College Park; disability advo- intravenous infusion. Two muscle biopsies statin-inhibitor and the upcoming clinical cate for Independence Now; and socio- are optional. Patients should have an aver- trials. political advocate for Persons with age muscle strength grade of 3. As a gen- On May 3, 2005 several patients with Disabilities. eral rule, patients should be able to walk FSHD reported on the FSH Society bul- Karen was 1993 and 1994 Ms. Wheel- 30 feet unaided except for use of orthotic letin board that they had begun the myo- braces, e.g. AFOs. statin inhibitor trial at Children’s DC and chair Maryland, and assisted me in run- Wyeth-Ayerst sites for myostatin Johns Hopkins. The trial is no longer a ning the program for six years. She was inhibitor MYO-029 clinical trial list based dream but now reality! The Society gives director of the Mid-Atlantic FSH support on my best information to date: Brigham thanks to the two support groups and their group and was a strong presence in Jerry and Women’s Hospital, Boston (Anthony leaders, those who sent in photographs, Lewis’ MD Telethon for many years. Karen Amato); University of Rochester, and those who responded immediately to counseled numerous people throughout Rochester, New York (Rabi Tawil); Wash- participate in the study. You have made the world via Internet, in person and ington University, St. Louis, Missouri this possible. through telephone contacts. She was pres- (Alan Pestronk); Johns Hopkins’ Medical, I hope that many of you will see the ent at the signing of the Americans with Baltimore, Maryland (Kathryn Wagner); value of my work and the need for dona- Disabilities Act at the White House and Kansas University Medical Center, Kansas tions and contributions to fund more peo- gave numerous testimonies for FSH MD City, Kansas (David Saperstein); Universi- ple working along side me in the FSH issues before Congress. Karen was on the ty of Utah, Salt Lake City, Utah (Kevin Society to help get the word out and show board of directors for the FSH Society, and Flanigan); Children’s Hospital DC, Wash- how remarkably effective we are. ington DC (Diana Escolar); Ohio State continued on page 6 6 FSH WATCH NEWSLETTER SUMMER 2005

Johnsen, cont. from page 5 In Memoriam former chairwoman of the Prince George's County Commission on Disabilities. She William T. Michael 1969-2004 designed and produced publications for William “Billy” T. Michael, son of the FSH disability awareness, research and Society board member William G. Michael, died resources. Karen also enjoyed entertaining on December 7, 2004 just a few months shy of and counseling visitors from national and his 36th birthday. Though FSHD determined international locales in her home. many events in Billy’s life, it did not determine Karen is survived by her loving family the type of person Billy was. At eight years old, which includes her son and two brothers Billy was able to participate in his town’s Little with FSHD. A memorial service was pro- League program. However, by eleven, Billy was vided to an overflowing crowd of family, unable to walk and began using a wheelchair. friends, and those whose lives she Not only did Billy graduate from high school touched. Despite the continuing progres- but he attended a few years of college, though he did not graduate. FSHD never affect- sion of this disease, Karen accomplished ed his high intelligence. Billy loved hamburgers and pizza but the effects of FSHD pre- more in her brief life than many people vented him from enjoying these foods as he grew older. with lesser difficulties. She always did her At twenty, he attended the first meeting which ultimately led to the FSH Society. He best to keep a positive attitude towards life was unable to participate fully in the Society but, in his father’s words, he “was always and to reach out to help others. pulling for us.” From birth, Billy’s mother, Ginny, realized that Billy had some weakness Prior to Karen’s death, she encouraged in his face and was unable to smile. Repeatedly, doctors dismissed Ginny’s concern and, me to continue her dream of a cure for repeatedly, the Michaels were given the wrong diagnosis for him. FSHD by raising funds for research. As Finally, Boston Children’s Hospital gave Billy a muscle biopsy test, as DNA tests stated in the 1999 article, it is very impor- were not available back then. In 1973, at four years old, Billy was diagnosed with FSHD tant that all of us do everything possible to in what appears to be a de novo case. Billy had a very severe case of FSHD. Billy had to wipe out this disease which takes away so have a gastrostomy in 1992 and a tracheostomy in 2001. The gastrostomy almost took much of a person’s dignity and quality of Billy’s life but he was able to pull through. He spent time whenever possible on his com- life. To this end, I have vowed to follow in puter. Ultimately, FSHD stole life from Billy. Billy is survived by his mother, father, and my daughter’s footsteps by dedicating this sister. We remember his kindness and his temperament which would “never allow him to year to bringing in the dollars for FSHD hold a grudge or be cross with . . . anyone.” research. A memorial fund to study infantile and early onset FSHD is being created in Billy’s At Karen’s memorial service, family memory so that we may fulfill our promise to him of a cure. Please contact Carol A. members announced Karen’s wish and Perez regarding this research fund. requested that, in lieu of flowers, they donate to the FSH Society for research in her memory. Although many donations The David and Helen Younger Research Grant were received, my goal is to raise $100,000 Sanford Batkin has established the FSHD pathogenesis. The overall hypothe- dollars in 2005. I recently sent a personal David and Helen Younger Research Grant sis is that the binding of the complex to contribution of $1,000 in Karen’s name. in honor of his daughter and grandson. Mr. the normal heterochromatic D4Z4 region After contacting the Kiwanis of the Sev- Batkin has been a staunch supporter as is abrogated in the contracted, ern, they donated $250. I plan to contact has his daughter Helen. In order to accel- hypomethylated, FSHD short repeat array. other organizations and businesses, and erate answers on FSHD research, Mr. Dr. Yokomori’s laboratory has produced will hold fund raising events throughout Batkin has generously established a considerable preliminary results to support the year. $60,000 fund. We are grateful to the binding of this complex to the D4Z4 My daughter, Karen, believed in angels, Batkin and Younger family for their com- repeat, and some of the main constraints and so do I. I hope that Karen’s life will mitment and their support. begin to appear in the form of a relation- inspire you to contribute to her dream and The first David and Helen Younger ship between repeat contraction, DNA Research Grant titled “The molecular char- and histone methylation. A very interest- to encourage others to do the same. Please acterization of the chromatin structure of the ing and peculiar finding in the preliminary be an angel for FSHD research. Send your D4Z4 repeat associated with FSHD” has results thus far is that HP1 and cohesin contributions and make checks payable to been awarded to Kyoko Yokomori, Ph.D., binding in a chromosome 4 FSHD patient FSH Society Research, in memory of University of California, Irvine, CA. seems fully abolished rather than dimin- Karen Lynne Johnsen, and send to Carol The main focus of this research project ished as the intact normal chromosome 4 A. Perez, Executive Director, FSH Society, is to study the role of the cohesin/HP1 version should still give binding. (Please Inc., 3 Westwood Road, Lexington, MA complex in the molecular organization of see grant details and abstract on page 11.) 02420 USA. the D4Z4 heterochromatin and its role in FSH WATCH NEWSLETTER SUMMER 2005 7 Gala Benefit Evening to Support the FSH Society Research an Outstanding Success In the autumn of 2003, Hanna concert. Dan remembered that Hanna’s Fund Continuing Research by the FSH Lachert, a violinist with the New York husband, David Segal, is a luthier and that Society was held at Symphony Space in Philharmonic Orchestra, contacted the William Monical, a restorer of historical New York City. Hanna asked her fellow FSH Society. Hanna later wrote about how stringed musical instruments and a New musicians from she found the Society and how she was Yorker, had a direct interest in FSHD. In the New York moved to action to help FSHD research: addition, for some time there had been Philharmonic “About three year ago, I had heard for the several Wall Street executives with inter- Orchestra to first time the letters FSHD. It was difficult ests in FSHD that the Society needed to donate their time to remember, and nobody knew what they pull together. Dan suggested to Carol that to perform at this stood for. The respected professionals, doc- she ask these individuals if they would benefit. Steven tors, friends had no clue. I went on line work with Hanna on a benefit concert. Blier donated his trying to find information. I came across Hanna wrote in her welcome to the time and talent by the FSH Society web site benefit concert; “The dynamic executive accompanying [www.fshsociety.org]. It was an eye opener. director of the FSH Society, Carol Perez, singer Hugh Rus- Two key words seemed to stand out: PRO- supplied a list of people in the metropoli- sell on the piano. GRESSIVE, and THERE IS NO TREAT- tan area who, like me, were looking for a The result was a MENT. This was alarming and not way to help. We formed a committee and flawless evening of Welcome from William acceptable to me. The FSHD was present set out to work.” Behind this dedicated music and song. Monical, New York, in my family and I had to find a way to group, the driving force was the shared The sold out Gala Benefit Co-chair help. It is pretty clear, that the ONLY way commitment to working for a cure for Benefit Evening of Chamber Music and for a cure will be coming from medical FSHD which affected their friends, their Song became the FSH Society’s first annual research. The FSH Society is responsible family and their colleagues. Other com- benefit concert, raising more than $63,000 for so much good work in that direction, mittee members were co-chair William to fund research. The evening was extraor- from years of educating Congress (success- Monical, Steven Blier (artistic director of dinary for both the performers and the fully), to sponsoring and developing the the New York Festival of Song), Jennifer audience. research and organizing nationwide sup- Egert, Christopher Eklund, Kathleen and The program was exquisite. An intro- port groups. I called them up and offered Joseph Friedman, Susan Glasser, Allan Sil- ductory remark and touching and moving what I know best, my music making.” verstein, Jennifer Burgess Valentine, and speech was given by Mr. William Monical, After that first call, Carol Perez (Exec- executive director, Carol Perez. of William Monical & Sons, on the special utive Director of the Society), Dan Perez After six remarkably busy months of nature of the concert and the serendipity (President and CEO), and the Society’s work by the team headed by Hanna and hard work that made this concept a Board of Directors discussed how a com- Lachert and William Monical, on Wednes- reality. Following the beautiful concert, mittee could be formed and resources day, March 24, 2004, the Gala Benefit there was a catered reception which brought to bear to help promote a benefit Evening of Chamber Music and Song to included event prizes and gifts. All Gala Benefit photos courtesy of photographer Diane Bondareff Program and Performers The first piece was Wolfgang A. Milwaukee Symphony - with whom she Mozart, Quartet in D KV 285 for flute, recorded a number of works by Dvorak violin, viola and violoncello. Allegro, and Kodaly. Adagio, and Rondeau. Performers were Fiona Simon, violinist, a member of Mindy Kaufmann, Fiona Simon, Irene the Orchestra since 1985, made her Phil- Breslaw, and Evangeline Benedetti. harmonic solo debut in November 1989, Mindy Kaufmann, flutist, joined the performing Vivaldi's Concerto for Three New York Philharmonic in 1979 at the Violins. Ms. Simon began her career in her age of 22. She has played as a soloist native England, where she studied with with the Orchestra with Zubin Mehta Szymon Goldberg and won major prizes in and Kurt Masur. Ms. Kaufman received the Carl Flesch and Jacques Thibaud com- a bachelor of music from the Eastman petitions. For three consecutive years, she School of Music, and, at the age of 19, was London's Young Artist of the Year. She won her first audition for a position has performed with the Academy of St. with the Rochester Philharmonic as Martin-in-the-Fields, the Royal Opera at Second Flute. Two years later, she Covent Garden and with the English became Piccolo and Assistant Principal Chamber Orchestra, among others. Flute. She has played with the Boston Irene Breslaw, a former Naumburg Symphony Orchestra, and with the continued on page 8 8 FSH WATCH NEWSLETTER SUMMER 2005

Gala Benefit, continued from page 7 gave a beautiful heart- where Mr. Blier played both piano and warming and soul- harpsichord. Mr. Blier is the artistic direc- touching introduction tor of the New York Festival of Song as to his choice of (NYFOS) which he co-founded in 1988 musical pieces and with Michael Barrett. Since the Festival's how they reflected on inception he has programmed, performed, his journey and strug- translated and annotated over ninety gle with his own vocal recitals. Mr. Blier is on the faculty of FSHD. the Julliard School. A native New Yorker, Hugh Russell, the he received an Honors degree in English young Canadian bari- Literature from Yale University. tone, has won praise The third piece was Franz Schubert’s for his handsome Trio in B flat Major op. 99 for piano, violin Mozart Quartet – (Left to Right) Mindy Kaufman, Flute; voice, inci- and cello. Allegro mod- Fiona Simon, Violin; Evangeline Benedetti, Cello; Irene Breslaw, Viola sive musi- erato, Andante un poco Scholarship winner and graduate of The cianship mosso, Scherzo. Alle- Julliard School, joined the viola section of and strong stage presence. gro, Rondo. Allegro the New York Philharmonic in August, While an Adler Fellow with the vivace. Performers were 1976. She was named Assistant Principal San Francisco Opera, Mr. Rus- Helene Jeanney, Hanna Viola in 1989. Prior to joining the Orches- sell appeared in Il barbiere di Lachert and Qiang Tu. tra, Ms. Breslaw was a member of both the Siviglia, Ariadne auf Naxos and Helene D. Jeanney, St. Louis Symphony and Baltimore Sym- in St. François d'Assise. As a a native of Paris, France phony. In May 2001, Ms. Breslaw celebrat- member of the Pittsburgh is a graduate of the ed 25 years as a member of the New York Opera Center he sang many Paris Music Conserva- Philharmonic. roles, including Malatesta in tory. She has studied at Evangeline Benedetti is one of the Don Pasquale, Guglielmo in the Mozarteum Acade- first women cellists to have become a Cosi fan’tutte, Pelleas in Pelleas my in Salzburg, the member of the New York Philharmonic. et Melisande, Nick Shadow in Banff Center of Fine She has appeared regularly with the Phil- The Rake's Progress, Eisenstein Arts, and Indiana Uni- harmonic Ensembles series at Merkin Con- in Die Fledermaus, and Taddeo versity. Ms. Jeanney has cert Hall in New York, including in L'italiana in Algeri. been awarded prizes in performances with guest artists Yefim Steven Blier enjoys an emi- Soloist Hugh Russell – Baritone several competitions: Bronfman, Vladimir Feltsman and Jerome nent career as an accompanist Alfred Cortot Competi- Lowenthal. and vocal coach. tion (Milano, 1979); Epinal Competition The Among the many (Epinal, 1983); Robert Casadesus Compe- second set artists he has part- tition (Cleveland, 1985); Thomas Richner of pieces nered with in Competition (New York, 1988); Chopin were for recital are Samuel National Competition (Miami, 1990); The voice and Ramey, Lorraine New York Chopin Association (New York, piano and Hunt Lieberson, 1990); and the East and West Artists included Susan Graham, Audition for a New York Debut recital in Prendiditos Frederica von Weill Recital Hall at Carnegie Hall (New de la mano Stade, Jessye Nor- York, 1991). (Miquel man, Wolfgang Hanna Lachert, a Polish-born and Camino) Holzman, New York-based violinist, leads a busy and and Can- Susanne Mentzer, versatile professional life. She plays more cion del Sylvia McNair than 130 concerts annually with the New carretero and Arlene Auger. York Philharmonic as well as performing Performers (Left to Right) Steven Blier, Piano In concert with with various chamber music groups and as (Gustavo and Hugh Russell, Baritone Caraballo) Renee Fleming, he a soloist. Ms. Lachert played her New York by Carlos Lopez-Buchardo; Pampamapa has performed throughout North America debut in 1972 (under the auspices of (Hamlet Luis Quintana) by Carlos Guas- and Europe, including a recital at La Carnegie Hall and Jeunesses Musicales), tavino; and Por una cabeza (Alfredo Le Scala, Milan and a Live From Lincoln and has given concerts throughout the Pera) by Carlos Gardel. Performers were Center telecast. His collaboration with United States ranging from a recital in Hugh Russell (voice) and Steven Blier Cecilia Bartoli began in 1994, and has Carnegie Hall, which was broadcast (piano). Before performing, Steven Blier included an appearance at Carnegie Hall continued on page 9 FSH WATCH NEWSLETTER SUMMER 2005 9

Gala Benefit, continued from page 8 nationwide over ing family. public radio, to All hope is solo appear- to see this ances with the become an New York Phil- annual harmonic event and (under Zubin that we Mehta), New continue to Jersey Sympho- replicate ny, and the this kind of Manchester event in Festival Orches- other cities tra among oth- in the com- ers. Ms. Lachert Trio (Left to Right) Hanna Lachert, Violin; ing year. has performed Helene Jeanney, Piano; Qiang Tu, Cello worldwide in five continents. She was soloist with Pol- ish, Belgian, German, Israeli, and Mexican Benefit Reception (From Left) Helene Jeanney, Pianist in Trio, orchestras and has made many television and Christopher Eklund, Benefit Committee and radio appearances. Ms. Lachert plays Followed Program on a violin made in 1982 by her luthier The FSH Society has already funded tion in FSHD with emphasis on stem cell husband, David Segal. two grants from the Gala Benefit Evening research. Dr. Rudnicki is a world- Since arriving in the United States in of Chamber Music and Song thanks to the renowned stem cell researcher. 1987, Chinese-born Qiang Tu has estab- The second research grant was award- lished himself as a multifaceted artist ed to York Marahrens, Ph.D. Dr. much in demand. He won the San Ange- Marahrens will receive this fellowship lo, Texas, Symphony Young Artist Compe- grant for one year on his project titled: tition in 1987, and the Grand Prize in the “Testing whether D4Z4 perform long distance Downey Symphony Young Artist Competi- gene silencing via the chromosome 4 inactiva- tion of Los Angeles the following year. In tion network.” This work at the Depart- 1994, he served as Principal Cellist of the ment of Human Genetics, David Geffen Princeton Chamber Symphony. Mr. Tu School of Medicine, University of Califor- joined the New York Philharmonic in nia, Los Angeles will examine gene silenc- November 1995. After making his solo ing via arrays of long repeats and test for debut at age 13 in Beijing, Mr. Tu began a the presence of non-random mono-allelic two-year engagement as soloist with one of gene silencing - a phenomenon recently China's major symphony orchestras. At discovered in mammalian autosome type age 17, he was awarded England's chromosomes. Menuhin Prize as a member of the China Both researchers and institutions are Youth String Quartet, and was later select- William Monical and Hanna Lachert, world class and focus on two fundamental- ed by the Chinese government to study in Co-chairs of the Benefit Committee the Sydney Conservatory. The Gala Benefit Evening was a huge excellent work of the Gala Committee. success for many reasons. People united The grants are named the FSH Society over music to support FSHD research and NYC 2004 Symphony and Song Benefit the work of the FSH Society. At the recep- Concert Post-Doctoral/Research Fellow- tion, the concert goers mingled with the ship Grants. The first post-doctoral grant performers and the FSH Society was awarded to Daniela Oliveira, Ph.D. researchers who were in attendance. Many Dr. Oliveira will receive a fellowship grant remarked at how amazing it was to see a for one year on her project titled: “Identifi- smaller set of New York Philharmonic per- cation of the mechanism regulating the Wnt- formers in such a small and intimate space dependent activation of muscle progenitor Front – Mr. and Mrs. Joseph Friedman, and described the concert simply as a cells.” Under the direction of Dr. Michael A. Rudnicki at the Ottawa Health Benefit Committee members with remarkable gem. There were many lively Dr. Petra Kaufmann and Dr. Michio Hirano, discussions, both on music and on Research Institute, Ottawa, Ontario, FSH Society Fellow, Columbia University research, and it felt like one large and car- Canada, the bulk of the work examines muscle cell differentiation and regenera- continued on page 10 10 FSH WATCH NEWSLETTER SUMMER 2005

Gala Benefit, continued from page 9 University; Dr. Cecilia Östlund, Columbia Monical, Anne Robinson, David Segal, University; Dr. Rossella Tupler, University Yaniv Segal, and David Thompson. of Massachusetts Medical School and the Last, the benefit committee consisted Institute of Medical Genetics at the University of Pavia, Italy; and Dr. Howard J. Worman, Colum- bia University. The benefit committee received helped from the follow- ing sponsors, to whom we express gratitude: Aegean Restaurant, @SQC Restaurant, Carnegie Hall, Caprice Cafe, Feline Day Spa, Fidelity Investments Chari- table Gift Fund, Great Aunt Fan- nie's Attic, Henry's Restaurant, (Left to Right) Daniel P. Perez, FSH Society President (From Left) Judy Herzberg, OR and Joseph and and Dr. Howard Worman, FSH Society Fellow Marvin & Sons, The New York Kathleen Friedman, Benefit Committee Members Philharmonic, Geraldi Norton ly different aspects of the FSHD problem - Memorial Corporation, Martin and Suzi of: Hanna Lacher, Chair; William Monical, one is disease mechanism oriented and the Oppenheimer Philanthropic Fund, and co-Chair; Carol A. Perez, Executive Direc- other more globally therapeutic and clini- The Westerleigh Press. We thank the cal trials model following oriented vis-à-vis contributors: pathways that Noa Ain, might lead to simi- Diane Bon- lar trials such as dareff, the upcoming William inhibitor of myo- Egert, Susan statin trial. It is Egert, Susan truly amazing what Glasser, Ben a small but dedi- Schonzeit, cated group can and Judith accomplish. We (Left to Right) Dr. Cecilia Östlund, FSH Society Fellow, Seslowe. are very grateful to Columbia University; Daniel P. Perez, FSH Society President; We thank the committee for Peter Wiese, CT the perform- this good work and (Left to Right) Dr. Howard J. Worman, FSH Society Fel- ing artists of the New York Philharmon- offer our thanks for a job extremely well low, Columbia University; Jennifer Valentine, ic and the New York Festival of Song Benefit Committee & her husband Anthony Valentine done. for donating time and for their involve- Attending the concert were current ment with the benefit. Phyllis J. Mills gen- tor, FSH Society, Inc.; Steven Blier; Jen- and past FSH Society Research Scientists erously underwrote the major costs of nifer Egert; Christopher Eklund; Kathleen and Fellows: Dr. Michio Hirano, Columbia Symphony Space and the reception for & Joseph Friedman; Susan Glasser; Allan this benefit Silverstein; and evening. Jennifer Burgess Benefit vol- Valentine. unteers were: The benefit was Jodi Arrabito, the dream of Bill & Ann Hanna Lachert, a Brooks, Ted violinist with the Fairchild, New York Philhar- Gabriela monic Orchestra, Guadalajara, and we thank all Dona Kahn, those listed above, Janice Kraj- and who attended, nak, Lois (Left to Right) Dr. Rossella Tupler, FSH Society Fellow, for making it a Marsh, Philip Pavia, Italy and U. Mass, Worcester, MA; with reality! (Left to Right) The Egert Family, Mollie, Adam, Bill, & Allison Dr. Petra Kaufmann, Columbia University; Jennifer (Benefit Committee Member) and Suzanne Dr. Michio Hirano, FSH Society Fellow, Columbia University FSH WATCH NEWSLETTER SUMMER 2005 11 Current FSH Society Funded Research, Fellows and Small Grants Total grants to date: $1,245,212.84 D4Z4 at 4qter. I believe that the proposed project will make unique contributions to further understanding of the chromatin David and Helen Younger Research Grant structure of D4Z4 and its role in the development of FSHD and may lead to possible identification of new therapeutic targets. (See Grant: FSHS-DHY-001 article on page 6.) Research: Kyoko Yokomori. Ph.D., Associate Professor Institution: University of California, Irvine Department of Biological Chemistry Marjorie Bronfman Class College of Medicine Grant: FSHS-MB-010 240D Med Sci I Researcher: Richard Lemmers, MSc., Ph.D. Irvine, CA 92697-1700 USA (expected June 15, 2005) Project Title: “The molecular characterization of the chromatin struc- Institution: Leiden University Medical Center ture of the D4Z4 repeat associated with FSHD.” Dept. of Human Genetics $30,000 6/1/2005 – 5/31/2006 Year 1 Wassenaarseweg 72 $30,000 6/1/2006 – 5/31/2007 Year 2 PO Box 9503 Abstract/Goal: [Provided by applicant]: FSHD is an autosomal 2300 RA Leiden dominant hereditary neuromuscular disorder characterized by pro- The Netherlands gressive degeneration of the upper body muscles. The majority of Project Title: “Refinement of the FSHD critical region on 4qA chro- disease cases are linked to the deletion of the D4Z4 repeat array in mosomes.” the subtelomeric region of chromosome 4q (4qter). Since there $35,000 6/15/2005 – 6/14/2006 Year 1 appears to be no functional open reading frame in this region, it $35,000 6/15/2006 – 6/14/2007 Year 2 was hypothesized that the D4Z4 repeat plays a structural role in Abstract/Goal: [Provided by applicant]: FSHD is the third most governing epigenetic regulation of gene expression critical for common myopathy with an autosomal dominant mode of inheri- proper muscle cell differentiation and functions, and that the dis- tance. FSHD is caused by contraction of the polymorphic D4Z4 ease is caused by the inability of the shortened D4Z4 to form its repeat in the subtelomere of chromosome 4q and the exact patho- specialized chromatin structure leading to dysregulation of critical genic mechanism is still unclear. An identical and equally polymor- gene expression. However, the exact nature of this chromatin phic D4Z4 repeat is localized on chromosome 10, but this has structure, factors required for the regulation, and the target genes never been associated with FSHD. Our approach of detailed char- whose dysregulation may directly evoke disease pathogenicity, acterization of FSHD alleles and translating these observations to remain obscure. Therefore, it is vital to understand D4Z4 function disease mechanisms has provided robust mechanistic insight in in order to address the etiology and pathogenesis of FSHD. FSHD pathogenesis over the past years, including the mechanism We found using chromatin crosslinking and immunoprecipita- of mitotic D4Z4 instability (Lemmers et al. 2004a) and the recog- tion (ChIP) analysis that the heterochromatin binding protein nition of a bi-allelic 4qter variation (designated 4qA and 4qB) of HP1, and an essential protein complex required for chromatid which only the 4qA allele is associated with FSHD (Lemmers et al. cohesion termed “cohesin,” specifically bind to overlapping regions 2002). Moreover, our laboratory provided direct evidence for a within the D4Z4 repeat in human muscle cells. HP1 was shown to chromatin modification associated with the contraction of D4Z4 associate with centromeric heterochromatin through interaction repeats by demonstrating hypomethylation of D4Z4 in FSHD alle- with the methylated lysine 9 residue of histone H3, the hallmark of les (van Overveld et al. 2003). silenced chromatin, and recruit cohesin to centromeres in S. Through our expertise in pulsed-field gel electrophoresis pombe and chicken cells. Consistent with this notion, we detected (PFGE)-based FSHD allele characterization, we have become the H3K9 methylation in D4Z4. Intriguingly, both HP1/cohesin bind- international reference center for FSHD diagnosis with on average ing and H3K9 methylation at this region are lost in FSHD mutant 50 referrals of atypical FSHD patients each year and culminating cells in which the 4qter D4Z4 is deleted. These results provide the in a database of greater than l000 patient and control genotypes first direct evidence that 4qter D4Z4 is heterochromatic, and that for D4Z4 alleles on chromosomes 4 and 10. Our PFGE-based this special organization is lost in FSHD. Thus, our results provide D4Z4 examination has led to further refinement of minimal further insight into the molecular nature and pathogenic contribu- requirements to develop FSHD in several ways including exclusion tion of this unique repeat sequence in FSHD. of a region of 55 kb proximal to D4Z4 by identification of proxi- We hypothesize that human HP1 targets cohesin to D4Z4, and mally extended deletions in typical FSHD patients (Lemmers et al. together they mediate proper heterochromatin structure organiza- 2003). Moreover, and novel to this field, our analysis provides evi- tion required for normal D4Z4 function which is abrogated in dence that within an FSHD repeat, not all units are equal suggest- FSHD. To address this, we plan to carry out biochemical and cyto- ing that intrinsic differences between individual D4Z4 units within logical analyses of the mechanism and function of cohesin and one array may be important for FSHD pathogenesis (Lemmers et HP1 binding to D4Z4. Specific aims are 1. analysis of HP1/cohesin al. 2004a). binding to D4Z4 in normal and FSHD cells, 2. characterization of In the current application, I propose to further refine the min- the underlying mechanism and factor requirement for HP1/cohesin imal region necessary and sufficient to cause FSHD in two ways. binding to D4Z4, and 3. analysis of the effect of cohesin and HP1 First, I will precisely characterize three novel patients with an depletion on chromatin structure organization and function of continued on page 12 12 FSH WATCH NEWSLETTER SUMMER 2005

Grants, continued from page 11 unusual FSHD allele. Two of these alleles carry, analogous to proxi- mally extended deletions, deletions of sequences distal to D4Z4. Grant: FSHS-MB-009 The third pathogenic allele is highly unusual because preliminary Researcher: Alberto Luis Rosa, M.D., Ph.D. data suggest that it is located on chromosome 10. The analysis of Institution (1): Washington State University - Spokane these alleles will be combined by the full characterization of FSHD WSU Spokane Health Science and control alleles that display repeat exchanges between chromo- PO Box 1495 some 4 and 10. Moreover, I will focus on intrinsic sequence differ- Spokane, WA 99210-1495 USA ences between 4qA-, 4qB- and 10q-derived D4Z4 units, most Institution (2): Laboratory of Neurogenetics notably that of the most proximal unit, as we provided evidence Institute for Medical Research “Mercedes y Martín Ferreyra” for a linkage disequilibrium (LD) between this D4Z4 unit and the INIMEC-CONICET, National Research Council of Argentina distal polymorphism 4qA or 4qB (Lemmers et al. 2004a). Friuli 2434, I expect that this proposal will generate new and essential B Col. Velez Sarsfield, information on the minimal region that is required to develop 5016 – Córdoba, Argentina FSHD. Considering the complexity of the disease mechanism, fur- Project Title: “Role of nuclear localization signal (NLS) and H1/H2 ther refinement of these elements is essential for a better under- motifs in DUX4-mediated cell death.” standing of the primary pathogenic pathway and will assist future $43,750 8/1/2004 – 7/31/2005 Year 1 research strategies based on candidate gene approaches and devel- $14,690 8/1/2005 – 7/31/2006 Year 2 opment of appropriate cellular and animal model systems. (See Goal: To gain understanding on the molecular and cellular mecha- articles on page 17.) nism underlying the pathogenesis of human FSHD. To study DUX4, a putative double homeobox-containing protein encoded by a 3.3 kb polymorphic tandem repeat(D4Z4), at the locus Grant: FSHS-MB-007 FSHD1A on the human chromosomal region 4q35. It is hypothe- Researcher: Tonnie Rijkers, Ph.D. sized that abnormal temporal or spatial expression of DUX4 has a Institution:: Leiden University Medical Center toxic effect for muscle cells causing FSHD. The study will help Center for Human and Clinical Genetics identify the mechanism(s) by which DUX4 causes cell death. Wassenaarseweg 72 PO Box 9503 2300 RA Leiden Joint Grant: The Netherlands Delta Railroad Construction Class & Project Title:: “Mouse models to study candidate genes and epigenetic FSH Society Lewis Family Research and Education Fund causes of FSHD.” Grant: FSHS-DR-006A; FSHS-LEWI-002 $30,000 2/1/2003–1/31/2004 Year 1 Researcher: Emma Ciafaloni, M.D $30,000 2/1/2004–1/31/2005 Year 2 Institution: University of Rochester School of Medicine Goal: To initiate research on genotype/phenotype correlations in Department of Neurology successfully created new lines of animal models of FSHD. 601 Elmwood Avenue P.O. Box 673 Grant: FSHS-MB-008 Rochester, New York 14642 USA Researcher: Cecilia Östlund, Ph.D./Howard Worman, Ph.D. Project Title: “The course and outcome of pregnancy and delivery in Institution: Columbia University women with FSH Muscular Dystrophy.” Departments of Medicine and Anatomy and Cell Biology Total grant: $39,410 P & S 10-518 Delta Railroad Construction Class 630 W 168th St $13,074 1/1/2004 - 12/31/2004 Year 1 New York, NY 10032 USA (interrupt/extend) Project Title: “The role of DUX4 in FSHD.” Delta Railroad Construction Class $30,000 2/1/2003 – 1/31/2004 Year 1 $1,926 1/1/2005 - 12/31/2005 Year 2 $30,000 2/1/2004 – 1/31/2005 Year 2 FSH Society Lewis Family Research and Education Fund Goal: To initiate research on the role of DUX4, DUX4C and to $11,047 1/1/2005 - 12/31/2005 Year 2 examine the role of the nuclear envelope, nuclear lamina and FSH Society Lewis Family Research and Education Fund nuclear organization in FSHD. $13,363 1/1/2006 - 12/31/2006 Year 3 Goal: Very little is known about the course and outcome of preg- The FSH Society has been instrumental in the nancy and delivery in women with muscular dystrophies. Our cur- rent ability to efficiently counsel women with muscular dystrophies giant advances in research to find a cure for when pregnant or planning a pregnancy is very limited due to the lack of studies addressing the issue of pregnancy and delivery out- FSHD. We need your donations to continue the come in this group. No specific attention has been paid to the pos- fight! Please see donation form on back page. continued on page 13 FSH WATCH NEWSLETTER SUMMER 2005 13

Grants, continued from page 12 sible interaction between gestation and progression of the myopa- 4. that this also partially alleviates muscle atrophy, even in the thy. Objectives are: to increase our knowledge about the course absence of training; and 5. that this results in an increase in mus- and outcome of pregnancy and delivery in women with FSH mus- cle strength and clinical indices. This is an open label pre-post pro- cular dystrophy; to assess the effect of pregnancy, delivery and tocol examining the effects of six months creatine supplementation post-partum on the progression of muscle weakness and muscle in 10 patients with proven FSHD. ROS protection and damage pain and on quality of life in women with FSH muscular dystrophy; will be studied in conchotome biopsies of deltoid muscle atrophy and, to ultimately improve counseling, family planning and obstet- and its effect on body composition will be measured by whole-body ric management of women with FSH muscular dystrophy. quantitative magnetic resonance imaging (MRI). Muscle strength and effects on symptomatology will be quantified. We will compare Delta Railroad Construction Class pre-creatine results with those of control subjects, and examine Grant: FSHS-DR-006B Honoraria differences between post- and pre-creatine values. Researcher (1): Wendy M. King, PT This study has several possible benefits: it will contribute evi- Institution (1): Ohio State University dence of the therapeutic usefulness of creatine over a longer time 389 McCampbell Hall span than earlier studies; it will throw light on mechanisms of mus- 1581 Dodd Drive cle damage in FSHD; if ROS are indeed important then other Columbus, Ohio 43210-1205 USA compounds that reduce oxidative stress in muscle may be useful; Researcher (2): Shree Pandya, MS, PT lastly, the results will help in the design and interpretation of Institution (2): University of Rochester School of Medicine future placebo-control trials. Physical Medicine and Rehabilitation University of Rochester FSH Society Sam E. and Mary F. Roberts Rochester, NY, 14642 USA Foundation Grant for Nutrition Research Project Title: “FSHD physical therapy booklet/brochure and article for Grant: FSHS-SMRF-002 physical therapy journal.” Researcher: Sara Winokur, Ph.D./Ulla Bengtsson, Ph.D. $15,000 5/1/2004 – 4/30/2005 Year 1 Institution: 202 Sprague Hall Goal: Gather and review of literature/information related to FSHD Biological Chemistry natural history, surgical options, orthotics, rehabilitation, physical University of California, Irvine therapy interventions, role of exercise, hydrotherapy, pain, etc. Irvine, CA 92697 USA Review scientific literature, brochures and web sites of various Project Title: “Restoration of normal myogenic pattern in FSHD: A organizations from English speaking countries to assess the type nutritional approach.” and format of information already available. Draft, peer-review and $30,000 3/1/2003 – 2/29/2004 Year 1 publish booklet/brochure on FSHD and physical therapy and sub- $30,000 3/1/2004 – 2/28/2005 Year 2 mit journal article to Physical Therapy journal on P.T. and FSHD. Goal: A clinically oriented project to study patterns of FSHD myo- genesis in cell systems using compounds and nutritional agents Joint Grant: that affect methylation, oxidative stress, chromatin structure and muscle cell differentiation. A major goal of this project is to build FSH Society Sam E. and Mary F. Roberts Foundation an effective model system to assay target compounds effectively. Grant for Nutrition Research & FSH Society Lewis The objective of this study is to identify therapeutic compounds to Family Research and Education Fund treat FSHD that can be taken as part of a nutritional regimen. Grant: FSHS-SMRF-001; FSHS-LEWI-001 Nutritional compounds are selected based on functional impact on Researcher: Graham J Kemp, M.D. myogenesis, availability as nutritional supplement and expediency Institution: Faculty of Medicine for clinical trials. University of Liverpool Liverpool L69 3GA, UK FSH Society New York City Project Title: “Muscle damage by reactive oxygen species (ROS), muscle atrophy and effects of creatine supplementation in FSHD.” Symphony and Song Benefit Concert Total grant: $48,650 Grant: FSHS-NYSS-001 FSH Society Sam E. and Mary F. Roberts Foundation: Researcher: Daniela M. Oliveira, Ph.D. $35,000 1/1/2003 - 5/01/2005 Year 1.5 Institution: Ottawa Health Research Institute (interrupt/extend) 501 Smyth Road Lewis Family Research & Education Fund: Ottawa, Ontario $13,650 1/1/2003 - 5/01/2005 Year 1.5 Canada K1H 8L6 (interrupt/extend) Project Title: “Identification of the mechanism regulating the Wnt- Goal: This is a pilot study designed to test the following hypothe- dependent activation of muscle progenitor cells.” ses: 1. that muscle in FSHD shows evidence of damage by ROS in $30,000 1/1/2005 – 12/31//2005 Year 1 vivo; 2. that this is at least partly due to reduced anti-ROS protec- Goal: The overall goal of the project is to identify genes regulated tion; 3. that this is ameliorated by six months creatine treatment; continued on page 14 14 FSH WATCH NEWSLETTER SUMMER 2005

Grants, continued from page 13 by the Wnt signaling pathway that are responsible for the myo- FSH Society, Inc. Small Grants genic differentiation and proliferation of CD45+/Sca-1+ muscle Grant: FSHS-SG-029 cells. In addition muscle satellite cells, another stem cell popula- Researcher: Alberto Luis Rosa, M.D., Ph.D. tion within muscle (CD45+/Sca-1+ muscle cells) plays a physio- Institution: Washington State University – Spokane, WSU logical role in muscle regeneration. Identification of new Spokane Health Science, 310 North Riverpoint Blvd., PO Box therapeutic targets can be used to help stimulate the Wnt-target 1495, Spokane, WA 99210-1495 USA genes that might be used to enhance stem cell transplant in FSHD. Project Title: FSH Society Kiichi Arahata, M.D. Memorial (KAM) International Travel Fellowship Grant $1,506.02 7/2004 Grant: FSHS-NYSS-002 Goal: To assist with travel to the 7th annual Summer School in Researcher: York Marahrens, Ph.D./Nieves Embade, Ph.D. Myology to lecture on FSHD with J. Adoni Urtizberea, M.D. and Institution: Department of HumAn Genetics for travel to Mons-Hainut, Belgium via rail to meet with Alexan- David Geffen School of Medicine dra Belayew, Ph.D. on DUX4 and FSHD. University of California, Los Angeles Gonda Center, Room 4558 695 Charles E. Young Drive Grant: FSHS-SG-030 Los Angeles, CA 90095 USA Researcher: Silvere van der Maarel, Ph.D. Project Title: “Testing whether D4Z4 perform long distance gene Institution: Leiden University Medical Center, Dept. of Human silencing via the chromosome 4 inactivation network.” Genetics, Wassenaarseweg 72, PO Box 9503, 2300 RA Leiden, $22,652 11/1/2004 – 10/31/2005 Year 1 The Netherlands Goal: A high-risk and novel approach to understanding chromo- Project Title: Travel Grant some interactions, epigenetics, to test the hypothesis that long $1,184.97 11/2004 repetitive sequence on a chromosome, regardless of sequence, is Goal: To assist with travel to the annual FSH Society International tied into the network of long repeats responsible for chromosome Research Consortium Meeting as satellite to the ASHG. inactivation, and particular with FSHD the case of non-random mono-allelic autosomal inactivation. To test the hypothesis that the tract of D4Z4 repeats at 4q35 is tied into the chromosome 4 Grant: FSHS-SG-031 inactivation network and that D4Z4 deletions disturb chromosome Researcher: George W.A.M. Padberg, M.D., Ph.D. 4 inactivation resulting in abnormal gene expression. Institution: c/o Anjali Kali, Department of Neurology, 326, UMC St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands FSH Society Research and Education Fund Project Title: Travel Grant $1,656.19 12/2004 Grant: FSHS-FS-001 Goal: To assist with travel to the annual FSH Society International Researcher: Nieves Embade, Ph.D./York Marahrens, Ph.D. Research Consortium Meeting as satellite to the ASHG. Institution: Department of Human Genetics David Geffen School of Medicine University of California, Los Angeles Grant: FSHS-SG-032 Gonda Center, Room 4558 Researcher: Richard Lemmers, Ph.D. 695 Charles E. Young Drive Institution: Leiden University Medical Center, Dept. of Human Los Angeles, CA 90095 USA Genetics, Wassenaarseweg 72, PO Box 9503, 2300 RA Leiden, Project Title: “Tethering adenine (Dam) methylase to the 3.3-kb The Netherlands FSHD repeats to identify distant genes that physically come in contact Project Title: Research Publication Grant with the repeats.” $851.19 3/2005 $30,000 3/1/2003 – 9/30/2004 Year 1 Goal: To assist with publication, production and distribution of (interrupt/extend) doctoral thesis on FSHD. Goal: A high-risk and novel approach to understanding chromo- some interactions, epigenetics, gene expression in FSHD, and with which other parts of the chromosome(s) the FSHD chromosome 4 Grant: FSHS-SG-033 D4Z4 repeats are coming into contact. To locate the FSHD Researcher: Petra van Overveld, Ph.D. gene(s) that interact with the D4Z4 repeats by tethering bacterial Institution: Leiden University Medisch Centrum, Dept. adenine methylase to sequences in or near the 3.3 kb repeats and Urology/Endocrinology, Stafcentrum Endocrinologie C4-R, Albi- then identifying adenine-methylation at distant sites on the same nusdreef 2, 2333 ZA, Leiden, The Netherlands chromosome and/or other chromosomes. Project Title: Research Publication Grant $851.19 3/2005 Call the FSH Society office at (781) 860-0501 Goal: To assist with publication, production and distribution of for ideas on how you can be a part of doctoral thesis on FSHD. raising funds for research. continued on page 15 FSH WATCH NEWSLETTER SUMMER 2005 15

Grants, continued from page 14

Grant: FSHS-SG-034 Grant: FSHS-SG-035 Researcher: Silvana van Koningsbruggen, Ph.D. Researcher: Kristen Bastress and Marcy Speer, Ph.D. Institution: Leiden University Medical Center, Dept. of Human Institution: Duke University Medical Center, Box 3445, Durham, Genetics, Wassenaarseweg 72, PO Box 9503, 2300 RA Leiden, NC 27710 USA The Netherlands Project Title: Research Project Grant Project Title: Research Publication Grant $3,800 4/2005 $851.19 3/2005 Goal: To assist with travel to Leiden to research and collaborate Goal: To assist with publication, production and distribution of on non chromosome 4 linked FSHD samples with distal and proxi- doctoral thesis on FSHD. mal deletions in May 2005.

FSH Society Grant & Fellowship Applications: An Overview

The FSH Society offers basic research oclonal antibodies, recombinant DNAs, include salaries of the principal investiga- grants, and research and postdoctoral fel- and any propagatable cells) should be tor. Indirect costs are not allowed, but lowships to support research relevant to freely available to other investigators fol- fringe benefits are considered part of the understanding the molecular genetics and lowing publication. The Society's position is personnel costs and are acceptable. Grant cause of FSHD. that there be no restriction or proprietary applications should be completed and for- To obtain an application, please submit rights in materials produced with our sup- warded with 20 copies to the FSH Society. a letter of intent. The letter of intent port. If reprints are to be considered as part should contain a single page introductory Grant Applications of the application, please provide 20 copies cover letter plus a one or two page The Society's focus is on FSHD. for distribution. descriptive summary of the proposed Support will be for research projects Applications are reviewed by primary research - enough for a decision from the that will contribute to identifying and reviewers as well as by the FSH Society's Scientific Advisory Board. A well thought understanding the basic defect in FSHD. Scientific Advisory Board. The Society will out and tight rationale for a research proj- The maximum award for a regular notify the applicant about the funding ect can easily lend itself to one page. The research grant is $30,000. Grants are usu- decision by letter only. letter of intent may be submitted at any ally for one year, with the possibility of Research & Postdoctoral time to the FSH Society, attention: Dr. renewal for up to three years. Fellowship Applications David Housman, Scientific Advisory In addition to its regular grants, the Support will be for research projects Board Chairman. Society offers a special Delta Railroad Con- that contribute to identifying and under- Indirect costs are not allowed but struction Grant for innovative proposals standing the basic defect of FSHD. fringe benefits are considered a part of per- accelerating the discovery of a treatment Indirect costs are not allowed but sonnel costs and are allowed. and cure of FSHD. A Delta Award can be fringe benefits are considered part of per- Deadlines for receipt of both grant, funded for one year for up to $30,000 per sonnel costs and are acceptable. research and postdoctoral fellowship appli- year. Funded fellowships may be renewed for cations are: February 1, 2005 and August Areas of interest include tissue, cell a second year, subject to satisfactory 1, 2005. and molecular biology studies of FSHD, progress reports at nine months. Payment, if awarded, is made in two and the development of animal models for A reference sheet is enclosed with equal installments. The first payment is FSHD. Proposals are sought for research each fellowship application for use by executed on the activation date. The sec- that involves isolation and characteriza- three or more applicant-selected personnel ond payment is executed six months after tion of the causative gene(s) and under- acquainted with the applicant’s relevant the beginning of the award period. A standing of the genetic, neuromuscular experience. progress-to-date package will be sent at and developmental mechanisms of the dis- Applications should be completed to the end of nine months. The subsequent ease. Further, there is interest in the devel- include the applicant's curriculum vitae, year of funding will not be activated prior opment of gene therapy, and other plus that of the research sponsor, and for- to a review of the nine-month progress therapeutic programs that may arise from warded with 20 copies to the FSH Society. report and an explanation of changes that that understanding. If reprints are to be considered as part of the work necessitates or changes in specif- As the Society has limited funds, grants the application, please provide 20 copies. ic aims for the next year. The progress that are funded are considered “seed The Society will notify the applicant report is required at nine months after the money.” If the project shows promise, it is about the funding decision by letter only. start of each award period. hoped that other institutions will fund it Propagatable materials (including mon- thereafter. Generally the Society does not 16 FSH WATCH NEWSLETTER SUMMER 2005 First FSH Society Roberts Foundation Grant Awarded By Graham Kemp, M.D., body composition and structure. He is cur- particularly susceptible to a kind of dam- e-mail: [email protected] rently overseeing the expansion of the age called “oxidative stress,” which is I and my three colleagues in Liverpool, facilities at MARIARC with the purchase caused by chemicals produced in the body UK, are pleased to have been awarded the of two new magnetic resonance scanners. called “reactive oxygen species” (Barrett, first FSH Society Roberts Foundation Nutri- The fourth member of the team is Tawil, Griggs & Figlewicz, ‘FSHD myoblasts tion Research Grant (FSHS-SMRF-01), for Bryan Lecky, Consultant Neurologist at possess reduced resistance to oxidative stress’ a project entitled “Muscle damage by reac- our specialist neuroscience hospital, the in FSH Watch, Spring 2001, p.70). The tive oxygen species, muscle atrophy and effects Walton Centre for Neurology & Neuro- two lines of evidence are connected, as of creatine supplementation in FSH MD.” surgery, Liverpool. After medical training there is evidence that creatine supplemen- A port city on the northwest coast of at Cambridge and London, Dr Lecky held tation protects against damage by reactive England, Liverpool was the European end clinical and research positions in London oxygen species, although how this might of the transatlantic sea route to the USA, before moving to Liverpool in 1987. His work is also controversial. and may be known to some readers for its particular clinical expertise is in neuro- This pilot study, based at the Faculty of contributions to pop music in the 1960s. It muscular diseases, and he has extensive Medicine, University of Liverpool, was is home to a large civic university with a experience in clinical trials. designed to test several connected thriving medical school, and to some of This eighteen-month project combines hypotheses: that muscle in FSHD is dam- the country’s biggest and busiest hospitals. three of our main research interests: quan- aged by reactive oxygen species (ROS), at Three of the research team are based titative magnetic resonance methods, least partly due to reduced anti-ROS pro- in the Faculty of Medicine of the Universi- mechanisms of muscle damage, and the tection; that this is ameliorated by dietary ty of Liverpool. I am in the Department of therapy of muscle disease. It is a pilot supplementation with creatine, a natural Musculoskeletal Science. Having trained study designed to investigate two ques- dietary constituent which forms an impor- in medicine at Oxford and specialized in tions: how tissue damage occurs in the tant chemical component of muscle; and clinical biochemistry, I held research posi- muscle of patients with FSHD, and that creatine supplementation is associated tions at the Universities of Sheffield and whether adding a naturally-occurring sub- with an increase in muscle mass and Oxford before moving to Liverpool in stance called creatine to the diet can strength. 1996, where I am also Faculty Director of improve muscle strength and reduce tissue Progress was held up at first by delays Postgraduate Research. My main research damage. in the replacement of our magnetic reso- interests are in muscle biochemistry and The project arose from two lines of evi- nance (MRI) scanner, which is an impor- muscle diseases and their study by non- dence. The first was work on creatine sup- tant tool for assessing body composition, invasive magnetic resonance techniques, plementation. Creatine is found mainly in and also by a major institutional reorgani- and I take part in the outpatient clinical the muscle, where it plays a role in energy zation. After that necessarily slow start, we care of patients with muscular dystrophies. storage and use, and this makes it a popu- have now studied 10 FSH patients to com- Malcolm Jackson is Professor of Cellu- lar dietary supplement among athletes. pletion. Despite the suggestive evidence of lar Pathophysiology in the Department of There has been a lot of interest in possible earlier trials in mixed groups of patients Medicine. After training in biochemistry in use in therapy and it is currently under with muscular dystrophies, preliminary Surrey and London, he held research posi- trial in a number of different diseases. analysis has not shown significant effects tions in London before moving to Liver- Studies in mixed groups of dystrophies of creatine on measures of muscle pool in 1984, where he is a former Dean of (including some patients with FSHD) strength, physical function and well being, the Faculty of Medicine. Professor Jackson have found short-term improvements in nor on body weight or on a non-MRI has a longstanding research interest in strength and daily-life activities However, measure of body composition (bioimped- mechanisms of cell damage in muscle dis- this is not well established for FSHD itself ance). ease and ageing, particularly in the role of and there is a lot of argument about how it What remains to be completed is the “reactive oxygen species” (of which more might work. analysis of the MRI data, and the bio- below). The second line of evidence is from chemical measurements on the pre- and Neil Roberts is Director of the Univer- recent work, funded by the FSH Society, continued on page 17 sity’s Magnetic Resonance and Image showing that muscle cells in FSHD are Analysis Research Centre (MARIARC), which applies magnetic resonance meth- Second Sam E. and Mary F. Roberts Foundation Grant ods to research mainly in neuroscience. The Sam E. and Mary F. Roberts Foundation of Lawrence, Kansas, established a fund After training in physics in Liverpool, to study nutrition and FSHD. We are indebted to the board of the Roberts Foundation Cardiff and Aberdeen, Professor Roberts and its chairman, Susan Pogany, for this opportunity. held research positions at the University of Drs. Sara Winokur and Ulla Bengsston, University of California, Irvine (UCI), Durham and the University of California Irvine, California, United States, were the second recipients of the Roberts Foundation at Santa Barbara before moving to Liver- grant for their project, “Restoration of the Normal Myogenic Pattern in FSHD: A Nutritional pool in 1991, where one of his research Approach.” We are pleased to announce that the Sam E. and Mary F. Roberts Founda- interests is the mathematics of measuring tion continued funding on the project for a second year at an additional $30,000. FSH WATCH NEWSLETTER SUMMER 2005 17

Roberts Grant, cont. from pg. 16 Marjorie Bronfman Grant for Research on FSHD for 2005 The generosity and commitment of Mrs. Marjorie Bronfman to FSHD research started post-supplementation muscle samples. in 1997. To date, the Society has received $700,000. Mrs. Bronfman renewed her commit- This last phase has recently been delayed ment through 2007 of $100,000 per year. Through a review and recommendation of our by some (long-planned, but inconvenient) Scientific Advisory Board, grants are awarded for two-year research fellowships surgery to one of the investigators, but (US$30,000- US$35,000/year) for research projects that show extraordinary promise to work is now about to resume. The nega- find the cause of FSHD. This foresighted contribution significantly aids progress in FSHD tive preliminary results have a potential research and has already created advances worldwide. The FSH Society is deeply indebted positive importance, pointing perhaps to to Mrs. Bronfman and the Marjorie and Gerald Bronfman Foundation for this significant an abnormality of creatine uptake in opportunity to advance FSHD research. FSHD. In addition we will know soon whether the biopsy results show evidence of increased ROS damage, as we hypothe- size, which will be important for pathogen- Tenth FSH Society Marjorie Bronfman esis and possible therapy even if creatine supplementation turns out to have no Post-doctoral Research Fellowship Awarded influence. This study aroused much inter- The FSH Society is pleased to announce the commencement of another exciting est among the local FSHD community. For research project under the direction of Richard Lemmers, MSc., Ph.D. (expected June 15, the investigators it has been a valuable 2005), Leiden University Medical Center, Leiden, The Netherlands, titled: “Refinement of opportunity to work with our FSHD the FSHD critical region on 4qA chromosomes.” Dr. Lemmers is the recipient of the tenth patients, from whom we have learned FSH Society Marjorie Bronfman Post-doctoral Research Fellowship award. much, on research of potential importance This laboratory and, in part, Dr. Lemmers have been instrumental in the identification both theoretically and practically. of bi-allelic variation in the 4qter region and the documentation of the 4qA allele as asso- Abstract ciated with FSHD. The laboratory has access to more than 1,000 FSHD DNA samples and Title: “Muscle damage by reactive oxygen is the major referral center for diagnostics of FSHD. Dr. Lemmers has already used these species, muscle atrophy and effects of creatine samples to further delimit the FSHD interval by exclusion of a region 55kb proximal to supplementation in FSHD.” D4Z4 via an unusual patient with a deletion. It is these types of unusual patients which he Investigator: Graham J Kemp, M.D. proposed to continue to study as part of this fellowship. He has two patients with deletions Institution: University of Liverpool of sequences distal to D4Z4 and a third pathogenic allele which appears to occur on chro- “This is a pilot study designed to test mosome 10, the location of homologous sequences to D4Z4. (Please see grant details and the following hypotheses: 1. that muscle in abstract on page 11.) FSHD shows evidence of damage by reac- tive oxygen species (ROS) in vivo; 2. that this is at least due partly to reduced anti- ROS protection; 3. that this is ameliorated 7th & 8th Delta Railroad Tides Foundation Grant by six months of creatine treatment, and 4. that this also partially alleviates muscle Construction Company Matching Challenge atrophy, even in the absence of training; Research Fellowship The Tides Foundation of San Francisco and, 5. that this results in an increase in Grants Established has issued a challenge for the Society to muscle strength and clinical indices. This match the 2004 Tides Grant of $30,000 The FSH Society Delta Railroad Con- is an open label pre-post protocol examin- struction Company fellowship program with donations from new sources. We are ing the effects of creatine supplementation continues to help FSHD research efforts asking our community to help us meet this in 10 patients with proven FSHD (and dis- by awarding research grants that provide challenge so we may receive the matching ease controls [DM] and unaffected con- needed expansion of current work and grant from Tides. trols). ROS protection and damage will be innovative approaches in FSHD studies. studied in conchotome biopsies of biceps. In 2003, the Tides Foundation award- The FSH Society is indebted to the Muscle atrophy and its effect on body ed $30,000 to the FSH Society at the Delta Railroad Construction Company of composition will be measured by whole request of a Donor Advised Fund. The Ashtabula, Ohio, Larry and Ida Laurello, body quantitative magnetic resonance and their family for this groundbreaking Board of Directors of the FSH Society imaging (MRI).” effort on behalf of the FSHD community. moved to utilize this award to provide sup- The Society is pleased to have Dr. Initiated in 1998, the seventh (2003) and port to the Society’s on-going activities. Kemp and his colleagues at the University eighth (2004) grants along with the previ- of Liverpool, one of the foremost institu- The members of the FSH Society ous six Delta Railroad Research Fellowship tions in the world in state-of-the-art MRI express gratitude to the Tides Foundation Grants are yielding tremendous insights in and Magnetic Resonance Spectroscopy and for this gift that permits the FSH Soci- new and novel areas of FSHD research. (MRS), working on FSHD and applying We hope this collaboration will continue ety to pursue excellence in research and these new methods to examine and quan- and the members of the Society will con- education to support international collabo- tify critical areas of research. sider matching this $30,000 gift annually. rative efforts. 18 FSH WATCH NEWSLETTER SUMMER 2005 Senator Paul D. Wellstone Muscular Dystrophy Research Fellowships Available The FSH Society is pleased to inform NINDS-, or NICHD-funded Wellstone (one fellow for two years, or, one fellow for you that on November 30, 2004 the NIH MDCRCs. one year with different fellows each year). issued Notice NOT-AR-05-001 titled: Eligible candidates must hold a The applicants may request a sup- Senator Paul D. Wellstone Muscular Dys- research or health-professional doctorate plement formatted as a Research Career trophy Research Fellowships at Wellstone or equivalent and have completed three- Development Award on Grant Applica- MDCRCs. to-eight years of postdoctoral research tion Form PHS 398 (updated 9/2004) The Senator Paul D. Wellstone Muscu- experience at the time of the application. http://grants.nih.gov/grants/guide/ lar Dystrophy Research Fellowships are Tenure tract investigators are not eligible, notice-files/NOT-OD-05-006.html) prestigious awards to help attract top can- nor are individuals that have received Notice of award will be issued two didates and collaborators to the existing NIH career awards (e.g., K01 or K08) or months after favorable review. Wellstone MDCRCs with the aim of research project grants (e.g., R01 or R03). The structure of the position and expanding the centers themselves. The Candidates for this fellowship must be requirements are detailed; please read the goal of the fellowships is to increase the affiliated with one of the MDCRCs, either NIH web site page thoroughly. number of well-trained MD researchers as a postdoctoral fellow or research associ- http://grants.nih.gov/grants/guide/ with expertise in a wide range of topics. ate preparing to join one of the projects notice-files/NOT-AR-05-001.html The Wellstone fellowships are designed to funded as part of the MDCRCs, or as a support projects that are: led by senior current member of one of the centers. The postdoctoral fellows or non-tenure track Wellstone Fellow must devote 75% effort investigators; short term and exploratory; to the proposed research and training pro- meant to promote career development; gram. and promote collaborations by the Cen- Domestic and foreign fellows are ters. eligible. Foreign fellows should most likely NIH Funding Opportunities The principle investigator(s) of the be eligible/applicable as this is a supple- & Program Announcements Wellstone Centers will identify and work ment to an existing U54 center. The FSH Society’s work in Washington, with individuals for these awards. Individ- Applications should propose both a DC and Bethesda, Maryland over the last uals interested in the program should con- mentor at the parent MDCRC and an fifteen years continues to yield dividends tact the center principle investigators. The external collaborator. Collaborations are as the NIH announces the renewal of an centers, principal investigators, and NIH intended to be meaningful research inter- initiative to accelerate research on FSHD institute funding agencies include: The actions between the fellow and the collab- and all muscular dystrophies. The NIH is University of Pittsburgh, Joseph C. Glo- orator; simply sharing reagents is not requesting grant applications whose sole rioso, Ph.D., NIAMS; The University of considered to be adequate. The external purpose is to explore and develop research Washington, Seattle, Jeffrey S. Chamber- collaborator does not receive any portion that will broaden the base of inquiry on lain, Ph.D., NICHD; and The University of the fellowship award/funds. FSHD. of Rochester, New York, Richard T. Mox- For fiscal year 2005, $300,000 As you know, an extraordinary amount ley, III, M.D., NINDS. direct funding is available. Three grants of work, time and effort has gone into will be awarded, one at each MDCRC making these program announcements a Notice Number: NOT-AR-05-001 institution. $100,000 per year, for up to reality. We are pleased that the hard work Senator Paul D. Wellstone Muscular Dys- two years, includes salary for the fellow in of the FSH Society, the research and clini- trophy Research Fellowships at Wellstone accordance with the institution's estab- cal community, and the directors and staff MDCRCs. lished range, fringe benefits, and research of the NIH has resulted in the announce- Grant application deadline(s) Feb- expenses. ment of initiatives to help accelerate ruary 1, 2005, July 1, 2005, February 1, Two years of support may be progress on FSHD and MD. 2006, July 1, 2006. requested with each application. The FSH Society wants to help build Applications may be submitted by An MDCRC can receive concur- FSHD infrastructure and community by principal investigators with NIAMS-, rent support for only one Wellstone Fellow informing you of these important funding opportunities from the NIH. Again, these programs and all of our efforts will only be The New York Community Trust Foundation Grant as successful as the number of you who Since 2000, at the request of an anonymous donor, The New York Community Trust take the time, care and initiative to submit awarded an annual grant of $50,000 to the FSH Society, Inc. The Society is grateful for applications in sufficient numbers and with the continued generosity and respect demonstrated by this gift. We express our gratitude sufficient funding levels. The NIH hopes to our anonymous donor. that the FSHD research community will Honoring the memory of the FSH Society’s board member and Mid-Atlantic Support make a strong showing with numerous and Group leader, Karen Johnsen, our anonymous donor and the New York Community multiple applications from clinicians and Trust have designated the 2005 grant to be for documentation or data base development researchers. on respiratory problems with FSHD. continued on page 19 FSH WATCH NEWSLETTER SUMMER 2005 19

NIH Program Announcements, continued from page 18

PA-05-051 Mentored Clinical the United States or have been lawfully Investigator Career Development PA-05-052 Postdoctoral Fellowship admitted for permanent residence by the The grant funding announcement is Funding time of award. This mechanism has specif- sponsored jointly by NIAMS, NINDS, The grant funding announcement is ic academic degree requirements. NICHD, and ODS at the NIH. sponsored jointly by NIAMS, NINDS, Date Announced: February 11, 2005 NICHD, and ODS at the NIH. Expiration Date: March 2, 2008 PA-05-038: Muscular Dystrophy: Date Announced: February 11, 2005 Pathogenesis and Therapies Program Announcement: Mentored Program Announcement: Ruth L. Clinical Investigator Career Development The program announcement is spon- Kirschstein NRSA for Postdoctoral Fellow- sored jointly by NIAMS, NINDS, NICHD, Awards in Muscle Disease Research ships in Muscle Disease Research (PA-05-051) and NHLBI at the NIH. (PA-05-052) Date Announced: January 7, 2005 Application Receipt Date(s): Multiple Earliest Anticipated Start Date: dates, see announcement. Program Announcement: MD: Pathogen- December 1, 2005 esis and Therapies (PA-05-038) http://grants.nih.gov/grants/guide/ Expiration Date: December 6, 2007 pa-files/PA-05-051.html Program Dates: FY2005-2008 The announcement covers and Strong emphasis is placed on The announcement covers and describes one type of career development describes two types of career development FSHD in the program announcement; award. The individual Postdoctoral Fellow- awards. The first is the Mentored Clinical Regular grant application deadlines ship Award (F32) is issued under the aus- in February, June and October for three Scientist Development Award (K08) for pices of the Kirschstein-NRSA Act. The developing a career as clinician research years; proposed postdoctoral training must be Applications may be submitted by scientists. “The K08 supports a three-, within the broad scope of biomedical, four-, or five-year period of supervised for-profit organizations, non-profit organi- behavioral, or clinical research and must zations, public or private institutions, such research experience that may integrate offer an opportunity to enhance the fel- didactic studies with laboratory or clinical- as universities, colleges, hospitals, and lab- low’s understanding of the health-related oratories, units of state government, units ly-based research.” The second is the Men- sciences and extend his/her potential for a tored Patient-Oriented Research Career of local government, eligible agencies of productive research career. the federal government, foreign institu- Development Award (K23) for the clinically This announcement uses the Ruth L. trained professional interested in patient- tions and domestic institutions. Kirschstein NRSA for Individual Postdoc- For fiscal years 2005-2008 total oriented research. toral Fellows (F32) See: Under the PA-05-051, each participat- funds will depend on total applications ing institute has different parameters for and availability of funds. http://grants.nih.gov/grants/ The mechanisms of support will be the K08 and K23 awards e.g. limits on guide/pa-files/PA-03-067.html salaries, supplies. Potential applicants are the NIH Exploratory/Developmental encouraged to look through the program Research Grant Award (R21) and the FSHD is highlighted in the NIH Research Project Grant Award (R01) carefully and to visit each institute’s announcement. description of the award. mechanisms. R21 applications up to Regular grant application deadlines $275,000 direct costs for the two-year FSHD is highlighted in the in April, August, December. term of the grant. There is no cost limit announcement. Eligible organizations include for- for the R01 mechanism, however appli- profit organizations, non-profit organiza- Regular grant application deadlines cants requesting $500,000 or more in tions, public or private institutions, such as in February, June and October. direct costs for any year must obtain an universities, colleges, hospitals, and labora- agreement from the NIH to accept appli- Eligible organizations include tories, units of state government, units of cation. domestic, for-profit and non-profit organi- local government, eligible agencies and No limit on the number of scientifi- zations, public or private institutions such labs of the federal government including cally different applications that may be as universities, colleges, hospitals and labo- NIH intramural labs, foreign institutions submitted. ratories. and domestic institutions. Application materials are at: Trainees must be citizens or non- For candidates which will have http://grants.nih.gov/grants/funding/ citizen nationals of the United States, or received a Ph.D., M.D., D.O., D.C., phs398/phs398.html have been lawfully admitted to the United D.D.S., D.V.M., O.D., D.P.M., Sc.D., NIH internet hyperlink for States for permanent residence and have Eng.D., Dr. P.H., D.N.S., N.D., Pharm.D., PA-05-038: in their possession an Alien Registration D.S.W., Psy.D. or equivalent doctoral http://grants.nih.gov/grants/ Receipt Card (I-151 or I-551) at the time degree from an accredited domestic or for- guide/pa-files/PA-05-038.html of award. eign institution prior to activation of the This program announcement seeks award. grant applications covering the first four Earliest anticipated start December The individual to be trained must out of the five areas of the MDCC plan. 1, 2005. be a citizen or a non-citizen national of continued on page 20 20 FSH WATCH NEWSLETTER SUMMER 2005

NIH Program Announcements, continued from page 19 The MDCC national research plan covers and effort we have received from Senator opportunities might not have been devel- five broad areas and seeks expansion of Arlen Specter, Chairman of the Senate oped. research into 1. mechanisms of disease, 2. Appropriations Subcommittee on Labor, This is wonderful news for us. Many of screening and diagnosis, 3. treatment Health and Human Services, Education us have worked hard to get this far with strategies, 4. rehabilitation, quality of life and Related Agencies and his staff; mem- the NIH and we feel that several coordi- and psychosocial issues, and 5. clinical and bers of the U.S. Senate Appropriations nated efforts are responsible for this timely basic research infrastructure. subcommittee; Representative John initiative. We are delighted with these This program is a renewal of the Janu- Porter, Chairman, U.S. House Appropria- monumentally important and critical steps ary 4, 2001, “Program Announcement tions Subcommittee on Labor, Health and towards finding solutions for FSHD and all with Set-Aside (PAS) number PAS-01- Human Services, Education and Related MD. The FSH Society is pleased to share 041: Therapeutic and Pathogenic Agencies and his staff; and members of the this information as it represents a major Approaches for the Muscular Dystro- U.S. House Appropriations subcommittee. step forward in FSHD research opportuni- phies.” Without their understanding of our needs, ties. We are indebted for the strong support and their cooperation in our efforts, these

Daniel Paul Perez, President & CEO of The FSH Society Testifies Before Congress On April 1 and April 13, 2005 Daniel NIH in FSHD in nearly every year that we investigation, hearing or some other con- Paul Perez, President & CEO, The FSH have come before you. In April 2000, prior gressional action regarding the absolute Society testified before congress regarding to the passage of the MD-CARE Act 2001 failure of the NIH to increase funding in fiscal year 2006 appropriations for the NIH law, we testified that congressional direc- FSHD. We have been testifying and gener- Research Programs on FSHD. Below are tive on FSHD has been, and is repeatedly, ating report language and laws for a dozen excerpts of the testimony. For the com- ignored by the NIH. Since 2001, we have years and have done the yeoman’s share in plete text, log on to: been working closely with the NIH on the building the base for FSHD. Despite the http://www.fshsociety.org MD-CARE ACT 2001 law-mandated specific directions from the congress in “FSHD is the third most prevalent research plan. Prior to all of the activity report language as shown above and with a form of muscle disease. It affects 1/20,000 around the MD-CARE Act 2001, we public law and a federal advisory commit- people. For men, women, and children the noted then that the NIH is seriously out of tee on MD, the NIH has failed to follow major consequence of inheriting FSHD is compliance with the previous four years of through on improving FSHD research. a lifelong progressive, and severe loss, of Congressional Directives. Incredibly today, Despite our active involvement with the all skeletal muscles. Most people are famil- in the calendar year 2005 heading into the NIH, the NIH has made the grant review iar with DMD that affects boys. What they fiscal year 2006, the NIH still is out of process very secretive, has turned down are not aware of is, that in any given compliance and has an anemic portfolio opportunities to shed light on the grant moment, there are probably more individ- on FSHD. Going back in time, in 2000 we decision making process and still has not uals with FSHD alive than with DMD reported the NIH had not responded to responded to congressional letters and (14,800 vs. 11,000). Recently, the NIH the past and prior years of report language. inquiries on the lack of FSHD research in identified significant gaps in FSHD “We have worked hard to be sure that the NIH portfolio. [grants] and a preponderance of DMD our constituency understands and supports “I would like to illustrate what we have research grants, and reported that it only the doubling of the NIH budget and have done at the FSH Society to improve the has five active projects on FSHD in its been very successful in helping to grow the funding and portfolio of MD and FSHD. entire NIH-wide portfolio. NIH budget from $10.326 billion to The FSH Society has represented the “We have given testimony before the $28.649 billion. In the same period, we FSHD community of researchers and clini- U.S. Congress every year since 1994. We saw FSHD funding increase by about $1.3 cians by the following activities on the have submitted 26 written testimonies and million. This year we will spare you the Hill, in the districts, and at the NIH. The five oral testimonies to the U.S. Senate heartache of our personal story and the FSH Society was the first on the Hill and at and U.S. House Appropriations Subcom- pain and suffering our disease brings in its the NIH and before PPDMD and mittees on Labor, Health, Human Services train. This year we simply would like you MDAUSA for many years since 1993. The and Education and Related Agencies. We to ask the NIH ‘Where did the money Society has given nearly three dozen con- have had considerable report language that Congress appropriated and further gressional testimonies, in writing and in written in the appropriations budget from directed through appropriations report lan- person, before the committee to support the committees directed to the NIH with guage go?’ the doubling of the NIH budget and to regard to improving the portfolio at the “We formally request a congressional continued on page 21 FSH WATCH NEWSLETTER SUMMER 2005 21

Congressional Testimony, continued from page 20

NIH Appropriations History Source: NIH/OD Budget Office & NIH OCPL (Dollars in millions) Fiscal NIH Overall MD Research MD % FSH Research FSHD % FSHD % Year Dollars Dollars of NIH Dollars of MD of NIH 2000 $17,821M $12.6M 0.071% $0.4M 3.18% 0.0022% 2001 $20,458M $21.0M 0.103% $0.5M 2.38% 0.0024% 2002 $23,296M $27.6M 0.118% $1.3M 4.71% 0.0056% 2003 $27,067M $39.1M 0.144% $1.5M 3.83% 0.0055% 2004 $27,887M $38.7M 0.139% $2.2M 5.67% 0.0079% 2005E $28,495M $41.0M 0.144% $1.6M 3.90% 0.0056% 2006E $28,640M $42.2M 0.147% $1.6M 3.79% 0.0056% encourage spending on MD. The Society more than two dozen researchers in five iterate by dystrophy - the total grants has succeeded in achieving nearly a dozen years, leading to nearly seven dozen publi- awarded in 2004 were: 18 for DMD, two sections of report language in appropria- cations in top tier journals. The FSH Soci- for LGMD, one for DM, and one for tions reports. ety helps the NIH FSHD patient registry FSHD! The most recent year of funding “I have served on numerous NIH and existing Wellstone CRCs as a volun- data shows that the non-Duchenne mus- research and planning task forces. The teer health agency. cular dystrophy group is not doing well in Society has had countless hundreds of “As a grant agency, the FSH Society has terms of numbers of grants and funding. meetings with the directors, staff and pro- world-renowned and leading clinicians and We request a hearing that focuses on this gram officers of the NIH NINDS, NIAMS, researchers peer reviewing applications, issue with immediacy and attention to NICHD, NHGRI, ORD and the OD. I funding research, reviewing progress ameliorating this unequal growth. Oddly, served on the five year, long-range plan- reports and preliminary data and ideas. We there is an order of magnitude difference ning meeting for the NIH NIAMS in July, know and have comprehension on the between DMD and the entire complement 1999. I rewrote the MD-CARE Act 2001 quality of applicants and projects and data of all other dystrophies. bills to include all muscular dystrophies, being submitted to you in the NIH grant “What has happened in FSHD ages and genders, and to establish the applications for FSHD research. I have research in the five years since the MD- MDCC federal advisory committee with first hand knowledge of the research as CARE Act was signed, and what has hap- public members, and to establish five well as our Nobel-quality advisors. I can pened in the thirteen years since we first national centers for MD (not at the exclu- tell you that researchers of Wellstone, started asking NIH to invest and build the sion of the basic research), and much Nobel, and Howard Hughes stature work- FSHD portfolio? NIH has rejected nearly more. The Society has contributed to sup- ing on FSHD have had applications on four dozen grant applications on FSHD of porting two NIH-funded FSHD research FSHD rejected by the NIH. However, R03, R21, R01, P01, U54, NIH Director planning conferences (1997, 2000). I work their applications on other types of MD Pioneer Award Nominations mechanisms closely and collaboratively with NIH pro- have been funded by the very same and more. The funding track record gram directors. I serve on the MDCC at agency. speaks for itself. To date in FY2005 the the request of Secretary Tommy G. “An analysis was presented at the NIH has rejected every FSHD application Thompson and Dr. Elias Zerhouni. I December 2004 MD-CARE Act-mandat- it has received. It is difficult to attract helped write the MDCC NIH research ed MDCC meeting of the 164 grants in investigators to FSHD when there is no plan submitted to Congress in summer the NIH portfolio for future planning pur- money made available for them and it 2004. I continually encourage FSHD poses related to the five sections of the becomes a downward spiral to attract new researchers to submit NIH grant applica- MD research plan. and promising investigators. tions for R01, R21, R03, P01, U54, K, T, F “The details of the data of the 164 “The NIAMS is ostensibly the lead training and mentoring awards and Direc- grants as presented at the December 1, institute at the NIH on MD. After all of tor’s Pioneer Awards. 2004 MDCC for the grants with funding our efforts the NIH NIAMS now has only “The Society has given testimony start dates in 2004 shows 35 grants funded one research contract that it is co-funding before the Institute of Medicine (IOM) on for the 2004 year to that date. The count with NIH NINDS for FSHD for $186,233 improving the Center for Scientific Review by dystrophy for calendar year 2004 is: 18 per year. Not one single research grant for (CSR) grant review process for FSHD. for DMD, two for LGMD, one for DM, FSHD, the third most prevalent dystro- The FSH Society itself has funded $1.1 one for FSHD, seven for stem cell phy! The total MD portfolio ending million in $30,000-a-year fellowships to research, and six for other research. To re- continued on page 22 22 FSH WATCH NEWSLETTER SUMMER 2005

Congressional Testimony, continued from page 21 December 15, 2004 was 58 projects, Of that total amount FSHD received writes that as an ‘example, one or more of including Wellstone CRCs components for $1,572,853 for three grants, one contract the research projects may have very high a total of $14,992,725. and one-quarter of a Wellstone CRC. scientific merit but lack relevance or con- “The NINDS is the second largest “Astonishingly, the total NIH-wide tribute little to the Center [Wellstone] as a NIH contributor towards MD research spending on MD decreased from $39.1 whole; conversely, research projects with funding. The NINDS now has three million (FY2003) to $38.7 million relatively lower scientific merit may pro- research grants, one research contract, and (FY2004). Something is wrong with this vide necessary strengths to the other com- one-quarter of a Wellstone CRC for FSHD trend given the Appropriations Subcom- ponents of the Center, and make a major for a total of $1,386,620 in FY2004. The mittee’s interest in this area and the efforts contribution to the Center as a whole.’ total MD FY2004 portfolio reported Feb- of the patient and research communities This changing of the rules has not worked ruary 1, 2005 was 39 projects, including to shore up and improve MD research. in the favor of FSHD research and in fact Wellstone CRC components for a total of “Looking at the three existing Well- quite the opposite in round two of the $14,756,290. stone CRCs, the NIH NICHD is spending Wellstone evaluations. We ask the com- “The NICHD is third largest NIH con- $1,631,994, the NIH NIAMS is spending mittee to hold a hearing to more closely tributor towards MD research funding. $1,224,971, and the NIH NINDS is examine if scientific quality is abrogated by The NICHD does not have a single spending $1,462,151. Only one-quarter of a more subjective review standard. research grant or project directly focused the Wellstone CRCs funded by the NIH “Mr. Chairman, we are asking you to or covering FSHD, which is the third most NINDS specifically works on FSHD. One inquire about the abysmal performance prevalent dystrophy that affects both boys more Wellstone center is currently in the record in FSHD funding and FSHD ori- and girls. The total MD FY2004 portfolio process of being funded and none of the ented Wellstone CRCs by the NIH. Last, reported December 1, 2004 was 15 proj- work at the fourth Wellstone pertains to at the end of the day, we all recognize that ects, including Wellstone CRC compo- FSHD. Of $4,319,116 funded to the first simply not enough grants are being sub- nents for a total of $3,837,633. three Wellstone CRCs, only $365,538 is mitted by the extramural research commu- “The NHGRI is historically the fourth directly titled for FSHD. Only 8.46 per- nity to the NIH. Note that the NIH has largest NIH contributor towards MD cent of the total Wellstone expenditure is done nothing to date to specifically to research funding. The NIH NHGRI does being spent on the third most prevalent encourage or targeted to draw in FSHD not have a single research grant or project form of MD that affects both men and research applications in five or six years. directly focused or covering FSHD. The women. For most of FY2004, there was no active total MD FY2004 portfolio reported on “Mr. Chairman, we are troubled by the program announcement on the street in December 1, 2004 was one project (Z01- NIH grant review process used for the MD from the NIH giving researchers no HG000215-02), including Wellstone CRC Wellstone Center applications as NIH uses obvious avenues or handles to submit basic components for a total of $281,396. The a review process that deviates from its rig- research grants. project is Hereditary Inclusion Body orous adherence to stating that it funds “Of course, researchers are not restrict- Myopathy (HIBM) and HIBM is not a projects of the highest scientific merit. The ed from submitting applications and can type of MD. Wellstone applications are reviewed for always submit grants in the absence of a “The NIAMS, NINDS, NICHD, scientific merit and then the entire score is call for proposal but most look for a pro- NHGRI the four lead institutes on MD adjusted upward or downward based on a gram announcement or call for applica- reported a combined total of 113 projects ‘gestalt’ or an impression. The NIH tions as a signal of NIH interest. The NIH on MD totaling $33,869,044 in FY2004. NIAMS extramural program director continued on page 23

NIH Muscular Dystrophy and FSHD Appropriations History Source: NIH/OD Budget Office & NIH OCPL (Dollars in millions) Fiscal Total NIH NIAMS NINDS NICHD NHGRI NIH wide Year Dollars on MD Dollars on MD Dollars on MD Dollars on MD Dollars on MD Dollars on FSHD 2000 $12.6M $4.8M $4.9M $1.2M $0M $0.4M 2001 $21.0M $9.2M $8.2M $0.5M $0.3M $0.5M 2002 $27.6M $11.1M $9.8M $0.6M $2.3M $1.3M 2003 $39.1M $15.5M $13.2M $4.5M $2.1M $1.5M 2004 $38.7M $15.0M $14.8M $3.8M $0.3M $2.2M 2005ES $41.0M $16.3M $13.7M $4.8M $2.2M $1.6M 2005EN $42.2M $15.2M $16.6M $5.0M $0.3M $1.6M 2006ES $42.2M $15.2M $16.7M $5.0M $0.3M $1.6M FSH WATCH NEWSLETTER SUMMER 2005 23

Testimony, cont. from pg. 22 Senator Paul D. Wellstone Muscular is certainly not receiving enough grants Dystrophy Cooperative Research Centers Open applications for FSHD, but it also manages The first round of NIH Senator Paul model; regulatory gene cassettes for to reject almost every one of the scarce Wellstone MDCRCs to boost U.S. MD human muscle therapy; molecular patho- few being submitted by the top FSHD research were announced on October 14, genesis of DM; and a viral vector core to researchers in the world. It can be said 2003. The Wellstone centers are mandated make available gene transfer vectors to that the volunteer health agencies and by the MD-CARE Act passed by Con- other researchers. University of Washing- extramural community of researchers have gress. The Wellstone centers are designed ton has had success with viral vectors in done everything in their power to grow the to work individually and collaboratively. delivering genes to mouse muscle. This area of research and to promote new Their purpose and mission is to encompass center will embark on translational studies researchers and research projects. We have basic, clinical and behavioral research to accelerate the development of new been very successful as shown above and projects, and will be overseen by a steering therapies. need the NIH to capitalize on our success committee. The University of Rochester, New and investments. The NIH has recognized The Society had originally requested York, Richard T. Moxley, III, M.D, director. that there is a systemic problem and has the establishment of three-to-five centers The co-director of the center is Rabi even self-identified a significant gap as of research excellence (COREs) in the leg- Tawil, M.D. This center is funded by the relates to FSHD, but it has not stated islation and the NIH, in turn, used the NINDS at $1,462,151 for fiscal year 2004. what, and if anything, it intends to do to collaborative research centers CRC U54 Twenty-five percent of the budget is for ameliorate the unequal growth and oppor- mechanism to achieve the same. FSHD, and 75 percent is for DM. The center is titled the “Muscular Dystrophy tunity for muscular dystrophies other than NIAMS, NINDS and NICHD, and Cooperative Research Center.” Drs. Moxley DMD. parts of the NIH, funded three new CRCs and Tawil will be researching skeletal mus- “At the December 2004 MD-CARE in October 2003. The Wellstone Centers have approximately $1 - $1.4 million in cle at the cellular and molecular level for Act-mandated MDCC, the staff and direc- direct costs per center, per year, for five insight into what causes muscle wasting. tor’s of the NIH admitted there was a years. This center focuses on myotonic and problem in the gap with FSHD research. The first three centers, principal inves- FSHD. Dr. Moxley has an interest in IGF- The follow-up has been deferred to pro- tigators, responsible NIH institute funding 1 clinical trials beginning with DM. The grammatic staff and the implementation agencies, and areas of research include: center maintains a repository of cell lines, details of the pending MD research plan. The University of Pittsburgh, Joseph antibodies, tissue and data about gene The NIH did not say exactly when it C. Glorioso, Ph.D., director. NIAMS and expression for sharing with other would follow-up on funding new research NICHD are funding this center. NIAMS is researchers. in FSHD. The NIH has a history in FSHD contributing $1,224,971 in fiscal year The MDA announced that it would of committing to address this issue and 2004. This center is titled: “Gene and Cell provide $500,000 supplemental grants in never following through. The two prior Therapy of Duchenne Muscular Dystrophy.” total costs per center, per year, for three NIH-sponsored research planning confer- Areas of research cover engraftment of years for additional projects at each one of ences on FSHD are an example. Only a muscle stem cells; herpes virus vectors in these centers. minor fraction of the 2000 NIH planning functional genomics; preclinical gene ther- As an aside, when the MD CRCs were conference research plan developed by the apy AAV vectors for preclinical studies in first launched, they did not have the Sena- NIH has been implemented. At this point, a dog DMD; DMD and LGMD phase I tor Paul Wellstone designation from the we are unsure if the lack of FSHD gene therapy safety trials; and functional U.S. government and there was consider- research in the NIH portfolio is a problem genomic studies of early myogenic differ- able confusion among patients with MD as of miscommunication or perhaps more entiation (NICHD component funded). to whether these were federal NIH centers deliberate and calculated on the part of The University of Washington, Seat- or MDAUSA/Jerry Lewis centers. Since the NIH. tle, Jeffrey S. Chamberlain, Ph.D, director. the federal government mandated the name change this confusion has subsided. “We also ask that Congress request an This center is funded by the NICHD. This The MDAUSA has stated that it will not explanation from the program staff and center will conduct studies to develop new continue supplemental funding on future directors of the NIH NIAMS, NHGRI, gene therapies for DMD. The areas of research are: preclinical gene transfer in centers. OD and NICHD for the inability to do DMD; testing AAV vectors in K9 DMD better in the area of FSHD despite repeat- ed congressional requests. We implore Congress to request the NIH to specifically build the research portfolio on FSHD Do you have a few hours to give to the through all available means, including re- issuing specific calls for research on FSHD Society’s work? Many things can be done at an accelerated rate, to make up for his- torical and present neglect.” right from where you live. We need you!! 24 FSH WATCH NEWSLETTER SUMMER 2005

Overall NIH-Wide Muscular Dystrophy Appropriations History Source: NIH/OD Budget Office & NIH OCPL (Dollars in millions) Astonishingly, the total NIH-wide spending on MD decreased from $39.1 million (FY2003) to $38.7 million (FY2004). Something is wrong with this trend given the U.S. Congressional interest in this area and the efforts of the patient and research communities to shore up and improve MD research.

Participating FY 1987 FY 1988 FY 1989 FY 1990 FY 1991 FY 1992 FY 1993 FY 1994 FY 1995 FY 1996 FY 1997 ICs Actual Actual Actual Actual Actual Actual Actual Actual Actual Actual Actual NHLBI $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 NINDS 2.4 2.6 3.7 4.7 5.6 5.6 7.1 7.1 7.5 8.1 9.4 NICHD 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 NEI 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 NIA 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 NIAMS 1.3 1.4 1.0 0.8 1.2 1.1 0.9 1.1 2.3 2.4 3.0 NIMH 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 NHGRI 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 NCRR 0.9 0.4 0.9 0.0 0.0 0.4 0.4 0.6 0.7 0.3 0.3 FIC 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 OD 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 NIH * 4.6 4.3 5.6 5.6 6.8 7.2 8.4 8.9 10.5 10.8 13.7 *May not add due to rounding.

Participating FY 1998 FY 1999 FY 2000 FY 2001 FY 2002 FY 2003 FY 2004 FY 2004 FY 2005 FY 2005 FY 2006 ICs Actual Actual Actual Actual Actual Actual Estimate Actual Estimate Enacted Estimate NHLBI $0.0 $0.0 $0.0 $1.0 $1.1 $1.0 $1.0 $1.6 $1.0 $1.6 $1.6 NINDS 9.5 8.7 4.9 8.2 9.8 13.2 13.5 14.8 13.7 16.6 16.7 NICHD 0.9 1.0 1.2 0.5 0.6 4.5 4.7 3.8 4.8 5.0 5.0 NEI 0.4 0.3 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 NIA 0.9 0.9 0.9 1.3 1.3 1.2 1.2 1.6 1.2 1.7 1.7 NIAMS 3.7 5.4 4.8 9.2 11.1 15.5 15.9 15.0 16.3 15.2 15.2 NIMH 0.0 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 NHGRI 0.0 0.0 0.0 0.3 2.3 2.1 2.2 0.3 2.2 0.3 0.3 NCRR 0.3 0.3 0.4 0.4 1.4 1.6 1.7 1.6 1.7 1.7 1.7 FIC 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 OD 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.0 0.1 0.0 0.0 NIH * 15.7 16.7 12.6 21.0 27.6 39.1 40.2 38.7 41.0 42.1 42.2 *May not add due to rounding.

Tracking Muscular Dystrophy Funding in the NIH National Human Genome It is necessary for the FSH Society to NHGRI in 2003, the estimate was 2.1 mil- Research Institute Funding measure the success of the MD-CARE Act lion dollars. The actual was 0.3 million. In In response to our request for more for our testimonies before the House and the following year, the estimate was 2.2 information on MD funding at the Senate Subcommittees on Appropriations million and, again, the actual was 0.3 mil- NHGRI, their office and staff put together to ensure that funds are set aside for MD lion in 2004. The problem, as explained, the following information. research. The data gathering task is con- was that some of the research projects that Over the past year some of the projects founded by a budget reporting system that they reported on as relevant for MD were we reported on earlier have changed and has not been accurate. One example of the inaccurately coded. Congress, looking at at the same time we have implemented a difficulty in determining the actual dollars these charts of expenditures, makes the new budget reporting system that more spent on MD research in the NIH is best assumption that these figures accurately accurately portrays the work we are doing. explained by the following table for the reflect the institutes’ spending. FY 2003: David Bodine, Z01- NHGRI. The estimate for 2005 is 0.3 million. HG0000083-08, 100% of $2,110,844, has Looking at the past history of the Knowing that funds designated for MD MD listed in keywords. An estimate of NHGRI, the spending on MD went from research are often not used in such a man- $2,162,836 is listed for this Z01 FY04 0.3 million in 2001 to 2.3 million in 2002 ner, it becomes incumbent upon the Society which still shows MD in the keywords, and 2.1 million in 2003, making it appear to approach each researcher listed as being however, Dr. Bodine did not count MD in that their institute had a major push into funded for MD research and ask the ques- his percentage breakout using a new budg- MD research, when, in fact, it was a sub- tion, “Are you doing research on muscular et methodology this year, so we did not jective error in coding of the research proj- dystrophy?” When we have made such report anything in FY04 for this Z01. ect and, in turn, record keeping. The inquires in the past, and researchers have FY 2004: One project from Bill Gahl, NHGRI policy and program analysis told us they are not involved in MD 5% ($281,396) of Z01-HG000215-02 branch writes that there had been a dis- research or FSHD research, the Society has (total $5,627,928) was counted towards crepancy in the old reporting system, and gone back to NIH to report on the discrep- MD. That is all that was reported. Howev- the new one more accurately details the ancies. At the same time, we include these er, nothing in the Z01 description men- work that is being done in this institute for issues in our report to Congress as a tions MD. MD research. watch-dog agency. From Bill Gahl, on Z01 HG000215-02: If you look at the expenditure for the continued on page 25 FSH WATCH NEWSLETTER SUMMER 2005 25

NIH NICHD Muscular Dystrophy Portfolio View of Data Along Coding and Budget Parameters Source: NIH/OD Budget Office & NIH OCPL (In Dollars) The NICHD is third largest NIH contributor towards MD research funding. The NIH NICHD does not have a single research grant or project directly focused or covering FSHD, which is the third most prevalent dystrophy that affects both boys and girls. The total mus- cular dystrophy FY2004 portfolio reported December 1, 2004 was 15 projects, including Wellstone CRC components for a total of $3,837,633. NICHD PROJECTS CONCERNING MUSCULAR DYSTROPHY, FY 2004 Type Project Number PI Name Title Award Amt Institution Name RFA/PA # 5 F32HD043583-02 MERCHANT,AZIZ M Manipulation of Prenatal Stem Cell Transplant Biology $50,548 CHILDREN'S HOSPITAL OF PHILADELPHIA 1 F32HD047099-01 LOVERING,RICHARD M. The Role of Cytokeratins in Skeletal Muscle Injury $42,976 UNIVERSITY OF PA03-067 MARYLAND BALT PROF SCHOOL 5 R01HD023924-16 FALLON,JUSTIN R NERVE-MUSCLE SYNAPSE ORGANIZING $72,220 BROWN MOLECULES UNIVERSITY 5 R01HD023924-16 FALLON,JUSTIN R NERVE-MUSCLE SYNAPSE ORGANIZING $314,123 BROWN MOLECULES UNIVERSITY 2 R01HD031476-06AKAUFMAN,KENTON R Microsensor for Intramuscular Pressure Measurement $501,743 MAYO CLINIC COLL OF MEDICINE, ROCHESTER 5 R01HD031636-09 ENGVALL,EVA S LAMININ ALPHA 2 IN TISSUE REGENERATION $384,327 BURNHAM INSTITUTE 1 R01HD044011-01AHU,HUAIYU Molecular Studies of Brain Malformations $311,643 METROHEALTH MEDICAL CENTER 5 R21HD044891-02 HOFFMAN,ERIC P Contractures: Molecular Remodeling of MTJ and $164,000 CHILDREN'S HD02-022 Muscle RESEARCH INSTITUTE 1 U10HD045993-01 VAN DEN ANKER,JOHN N Washington D.C. Collaborative PPRU $364,077 CHILDREN'S HD03-001 NATIONAL MEDICAL CENTER 5 U54AR050733-02 GLORIOSO,JOSEPH C FUNCTIONAL GENOMICS STUDIES OF EARLY $249,999 UNIVERSITY OF AR03-001 MYOGENIC DIFFERENTI PITTSBURGH 5 U54HD047175-02 CHAMBERLAIN,JEFFREY S. PRECLINICAL GENE TRANSFER IN DUCHENNE $353,786 UNIVERSITY OF AR03-001 MUSCULAR DYSTROPHY WASHINGTON 5 U54HD047175-02 LITTLE,MARIE-TERESE TEST OF AAV VECTORS IN K9 DMD MODEL $355,168 UNIVERSITY OF AR03-001 WASHINGTON 5 U54HD047175-02 HAUSCHKA,STEPHEN D REGULATORY GENE CASSETTES FOR HUMAN $222,498 UNIVERSITY OF AR03-001 MUSCLE GENE THERAPY WASHINGTON 5 U54HD047175-02 TAPSCOTT,STEPHEN J MOLECULAR PATHOGENESIS OF MYOTONIC $222,498 UNIVERSITY OF AR03-001 DYSTROPHY WASHINGTON 5 U54HD047175-02 CHAMBERLAIN,JEFFREY S. VIRAL VECTOR CORE $228,027 UNIVERSITY OF AR03-001 WASHINGTON Grand Total 14 Projects$ 3,837,633

NHGRI Funding, continued from page 24 Our work is on a myopathy involving patients are significantly weakened and HIBM patients. Second, we are preparing a alpha-dystroglycan, which interacts with often wheelchair-bound. The defective clinical protocol to test the efficacy and dystrophin, the protein defective in the gene, GNE, codes for a bifunctional pro- safety of intravenous immunoglobulin as a classical muscular dystrophies. tein (UDP-GlcNAc 2-epimerase/ManNAc source of sialic acid for HIBM patients. Hereditary Inclusion Body Myopathy kinase) catalyzing the first two steps in the From David Bodine on Z01 (HIBM) is a late-onset, autosomal reces- synthesis of sialic acid. We have examined HG000083-09: In 2003 we were intrigued sive myopathy characterized by quadriceps several patients, verified their GNE muta- by the idea that hematopoietic stem cells sparing and the presence of vacuoles in tions, and made two contributions to the could differentiate into cells other than muscles. Onset occurs in the third decade, field. First, we showed decreased sialic acid blood. There were reports in the literature and by the end of the fourth decade, on the muscle alpha dystroglycan of three continued on page 26 26 FSH WATCH NEWSLETTER SUMMER 2005

NHGRI Funding, continued from page 25 about stem cells becoming skeletal muscle changed. I am now convinced that the stem cells in the lab. However this is not cells, and we had some data that cardiac new cells in the muscles are still so much to learn how they make muscle, muscle cells could come from hematopoi- hematopoietic cells, not muscle cells. but rather to see how similar they are to etic stem cells. However as we and others Thus, for 2004 we stopped linking our hematopoietic stem cells. They do express investigated this more closely, my interpre- research into hematopoietic stem cells to some of the same genes, but I do not think tation, and most other people's too, muscular diseases. We do study muscle we are ready to link our work to MD.

NIH NIAMS Muscular Dystrophy Portfolio View of Data Along Coding and Budget Parameters Source: NIH/OD Budget Office & NIH OCPL (In Dollars) The NIAMS is ostensibly the lead institute at the NIH on MD. The NIH NIAMS now has only one research contract that it is co- funding with NIH NINDS for FSHD for $186,233 per year. Not one single research grant for FSHD, the third most prevalent dystrophy. The total muscular dystrophy portfolio ending December 15, 2004 was 58 projects, including Wellstone CRCs components for a total of $14,992,725. Project Number PI Name Project Title Total Award SEA% SEA Code Total PCC

5-R01-AR-48902-03 BURKE BRIAN The role of nuclear lamins in muscle disease $306,069 100 $306,069 2 B 1-R01-AR-51199-01 CAMPBELL KEVIN P. Epsilon-sarcoglycan in LGMD Type 2D $346,625 100 $346,625 2 B 5-R01-AR-44533-09 CHAMBERLAIN JEFFREY S Assembly of the dystrophin associated protein complex $367,630 100 $367,630 2 B 5-R01-AR-40864-15 CHAMBERLAIN JEFFREY S. DYSTROPHIN REPLACEMENT IN MDX MICE $368,600 100 $368,600 2 B 1-R01-AR-50565-01 CLEMENS PAULA R Genetic Rescue of Dystrophic Muscle In Utero $250,036 100 $250,036 2 B 2-R01-AR-45653-06 COOPER THOMAS A Molecular Pathogenesis of Myotonic Dystrophy $394,857 100 $394,857 2 B 5-R01-AR-49043-02 COX GREGORY A Genetic Mechanisms of Muscular Dystrophy in Mice $383,050 100 $383,050 2 B 5-R01-AR-48179-04 CROSBIE RACHELLE H Structure-Function Analysis of Sarcospan $339,975 100 $339,975 2 B 5-R01-AR-49419-02 DUAN DONGSHENG Dual AAV Vectors for Duchenne Muscular Dystrophy Therapy $316,463 100 $316,463 2 B 5-R01-AR-42423-09 ERVASTI JAMES M CYTOSKELETAL INTERACTIONS OF DYSTROPHIN $296,725 100 $296,725 2 B 5-R21-AR-50717-02 ESSER KARYN A. Circadian rhythms in skeletal muscle: Role of Bmal $74,227 10 $7,423 2 B 1-R01-AR-49881-01-A1 GRANGE ROBERT W Pathogenic mechanisms that initiate DMD $321,970 100 $321,970 2 B 5-R01-AR-18860-28 HAUSCHKA STEPHEN D Muscle Gene Regulation and Cassettes for Gene Therapy $352,990 25 $88,248 2 B 5-R01-AR-49684-03 HUARD JOHNNY Muscle regeneration through stem cell transplantation $243,591 100 $243,591 2 B 1-R21-AR-51696-01 KHURANA TEJVIR S Extraocular muscle stem cells for DMD therapy $79,250 100 $79,250 2 B 5-R01-AR-48871-02 KHURANA TEJVIR S. Regulation of Utrophin Promoter in Muscle $335,228 100 $335,228 2 B 5-R01-AR-48171-05 KRAHE RALF Molecular Genetic Characterization of Myotonic Dystrophy $277,500 100 $277,500 2 B 5-P01-NS-40828-04 KUNKEL LOUIS M Gene expression in normal & diseased muscle development $300,000 100 $300,000 2 B 5-R01-AR-46792-05 LISANTI MICHAEL P CAVEOLIN-3 AND MUSCULAR DYSTROPHY $323,980 100 $323,980 2 B 1-R01-AR-50202-01-A1 MARTIN PAUL T Galgt2, dystroglycan, and muscle extracellular matrix $291,808 100 $291,808 2 B 5-R01-AR-50703-02 MCNALLY ELIZABETH M. GENE EXPRESSION IN LIMB GIRDLE MUSCULAR DYSTROPHY $159,444 100 $159,444 2 B 5-R01-AR-18687-29 MEISSNER GERHARD W REGULATION OF SARCOPLASMIC RETICULUM CA2+ RELEASE $415,851 25 $103,963 2 A 5-R01-AR-49496-03 MILLER JEFFREY B Pathogenesis of Laminin-alpha2 Deficiency $345,779 100 $345,779 2 B 2-R01-AR-39467-17 OLWIN BRADLEY B Analysis of Myogenic Growth and Differentiation $324,711 50 $162,356 2 B 5-R01-AR-49660-02 RUOHOLA-BAKER T HANNELE The Role of Dystroglycan in Signal Transduction $290,708 100 $290,708 2 B 5-R03-AR-48650-03 SMITH BRUCE F Molecular identification of canine dystrophinopathies $72,500 100 $72,500 2 B 3-R01-AR-46911-05-S1 SPENCER MELISSA J THERAPEUTIC APPROACHES FOR MUSCULAR DYSTROPHY $50,615 100 $50,615 2 B 5-R01-AR-46911-05 SPENCER MELISSA J THERAPEUTIC APPROACHES FOR MUSCULAR DYSTROPHY $295,850 100 $295,850 2 B 5-R01-AR-48177-04 SPENCER MELISSA J LGMD 2A protein calpain 3 and its binding to titin $362,188 100 $362,188 2 B 5-R01-AR-46799-05 SWANSON MAURICE S RNA DOMINANCE IN HUMAN DISEASE $231,392 100 $231,392 2 B 5-R01-AR-47292-05 SWEENEY H LEE BIOENGINEERING RESEARCH PARTNERSHIP--MUSCULAR DYSTROPHY $699,965 100 $699,965 2 B 5-R01-AR-45203-07 TAPSCOTT STEPHEN J Myotonic Dystrophy Locus Control $361,053 100 $361,053 2 B 1-R01-AR-51034-01 THOMAS GAIL D. Ischemia and the Pathogenesis of Muscular Dystrophy $342,160 100 $342,160 2 B 5-R01-AR-46806-04 THORNTON CHARLES A MODEL OF NEUROLOGIC IMPAIRMENT IN MYOTONIC DYSTROPHY $351,905 100 $351,905 2 B 5-R01-AR-49077-03 THORNTON CHARLES A RNA-mediated Mechanisms in the Myotonic Dystrophies $343,744 100 $343,744 2 B 3-R01-AR-47721-03-S1 TIDBALL JAMES G Myeloid Cell Function in Muscular Dystrophy $20,223 100 $20,223 2 B 5-R01-AR-47721-04 TIDBALL JAMES G Myeloid Cell Function in Muscular Dystrophy $423,254 100 $423,254 2 B 5-R01-AR-44387-08 TIMCHENKO LUBOV T Molecular Mechanisms of Myotonic Dystrophy $282,940 100 $282,940 2 B 5-R01-AR-49222-02 TIMCHENKO LUBOV T The Role of RNA-Binding Proteins in Myogenesis $282,940 100 $282,940 2 B 5-R01-AR-47664-02 VERGARA JULIO L Excitation-Contraction Coupling in Dystrophic Muscle $221,888 100 $221,888 2 B 5-R01-AR-49042-02 WANG EDITH H CHCR:A Protein in Mammalian Muscle Differentiation $253,111 100 $253,111 2 B 5-R01-AR-48997-02 WORMAN HOWARD J Pathogenesis of Emery-Dreifuss Muscular Dystrophy $345,803 100 $345,803 2 B 1-R01-AR-50595-01 XIAO XIAO Gene Therapy for a severe DMD Animal Model $340,471 100 $340,471 2 B 2-R01-AR-45967-06 XIAO XIAO AAV Vectors for Heart and Muscle Gene Therapy $331,217 100 $331,217 2 B 3-R01-AR-50200-02-S1 YOUNG STEPHEN G. Postisoprenylation Processing and the Nuclear Lamina $118,140 100 $118,140 2 B 5-R01-AR-50200-02 YOUNG STEPHEN G. Postisoprenylation Processing and the Nuclear Lamina $378,585 100 $378,585 2 B 1-R13-AR-51727-01 OMARY M BISHR 2004 Intermediate Filaments Gordon Conference $9,980 20 $1,996 2 B 5-K24-AR-48143-03 THORNTON CHARLES A Integrative pathophysiology of myotonic dystrophy $101,106 100 $101,106 2 B 1-K02-AR-51181-01 WANG YAMING Strategies to improve stem cell engraftment into muscle $106,920 100 $106,920 2 B 5-U54-AR-50733-02 GLORIOSO JOSEPH C. Gene and Cell Therapy of Duchenne Muscular Dystrophy $1,224,971 100 $1,224,971 2 A 1-F31-AR-52312-01 HUBAL MONICA J Molecular determinants of exercise-induced muscle damage $23,522 20 $4,704 2 B 5-T32-AR-48523-02 TERJUNG RONALD L Exercise & Health: Integration from Molecule to Patient $173,141 100 $173,141 2 A FSH WATCH NEWSLETTER SUMMER 2005 27

NIH NINDS Muscular Dystrophy Portfolio View of Data Along Coding and Budget Parameters Source: NIH/OD Budget Office & NIH OCPL (In Dollars) The NINDS is the second largest NIH contributor towards MD research funding. The NIH NINDS now has three research grants, one research contract, and one-quarter of a Wellstone CRC for FSHD for a total of $1,386,620 in FY2004. The total MD FY2004 portfo- lio reported February 1, 2005 was 39 projects, including Wellstone CRC components for a total of $14,756,290.

NINDS FY 2004 Muscular dystrophy 2/1/05 Indicates this project is also subcoded for FSHD Project No. PI Title Organization MD Funding 1F31NS047910-01 Garvey, Sean M. Patho-Genetic Explorations of Myotilin, the LGMD1A Gene DUKE UNIVERSITY$ 14,412

1F31NS049658-01 HIGASHI, MISAO E Minority Predoctoral Fellowship Program HARVARD UNIVERSITY (MEDICAL $ 30,190 SCHOOL) 1P01NS046788-01A1 FROEHNER, STANLEY C Molecular and Cellular Therapies for Muscular Dystrophy UNIVERSITY OF WASHINGTON$ 1,370,710

1R01NS044146-01A2 WILTON, STEPHEN D Antisense oligonucleotide suppression of DMD UNIVERSITY OF WESTERN AUSTRALIA$ 149,850 1R01NS048859-01 EHRLICH, MELANIE FSHD: Chromatin Structure, Looping, & TULANE UNIVERSITY OF LOUISIANA$ 296,941 Expression 1R01NS049635-01 RANUM, LAURA P DM2: Murine and cell Culture Models of CCUG RNA UNIVERSITY OF MINNESOTA TWIN $ 386,819 toxicity CITIES 1R13NS050966-01 GRIGGS, ROBERT C Pathogenesis and treatment of the periodic paralyses UNIVERSITY OF ROCHESTER$ 2,635 1U01NS046546-01A2 XIAO, XIAO AAV Mini-dystrophin Vectors for DMD Gene Therapy UNIVERSITY OF PITTSBURGH AT $ 313,076 PITTSBURGH 2L30NS050051-02 FLANIGAN, KEVIN M Translational Research in the Dystrophinopathies LOAN REPAYMENT APPLICATIONS$ 15,012 2P01NS026630-16A1 PERICAK-VANCE, MARGARET A Genetic Studies in Neurological Disorders DUKE UNIVERSITY$ 472,448 2R01NS033145-10 FROEHNER, STANLEY C Regulation of Syntrophin Function UNIVERSITY OF WASHINGTON$ 350,575 2R01NS038469-06 YURCHENCO, PETER D Laminin-Induced Membrane Complexes in Muscle and UNIV OF MED/DENT NJ-R W JOHNSON $ 161,817 Nerve MED SCH 5P01NS040828-04 KUNKEL, LOUIS M Gene expression in normal & diseased muscle CHILDREN'S HOSPITAL (BOSTON)$ 1,164,230 development 5R01NS029172-12 GRADY, RONALD M TRANSGENIC ANALYSIS OF SYNAPTIC PROTEIN WASHINGTON UNIVERSITY$ 269,500 FUNCTION 5R01NS035870-08 RANUM, LAURA P CLONING/CHARACTERIZATING A MYOTONIC UNIVERSITY OF MINNESOTA TWIN $ 285,996 DYSTROPHY LOCUS CITIES 5R01NS036409-07 RANDO, THOMAS A Oxidative Stress and Muscle Cell Death STANFORD UNIVERSITY$ 260,000 5R01NS039915-05 Wolff, Jon A GENE THERAPY FOR DUCHENNE MUSCULAR UNIVERSITY OF WISCONSIN MADISON$ 324,000 DYSTROPHY 5R01NS040718-04 RANDO, THOMAS A Cellular Signaling and Muscular Dystrophies STANFORD UNIVERSITY$ 292,500 5R01NS041116-05 REDDY, SITA MOLECULAR MECHANISMS WHEREBY CTG UNIVERSITY OF SOUTHERN $ 365,625 EXPANSION RESULTS IN DM CALIFORNIA 5R01NS042874-03 STEDMAN, HANSELL H. Surgical Approaches to Systemic Gene Transfer UNIVERSITY OF PENNSYLVANIA$ 376,438 5R01NS043186-03 MENDELL, JERRY R Gentamicin Trial in Duchenne and Limb Girdle Dystrophies OHIO STATE UNIVERSITY$ 445,131

5R01NS043264-03 FLANIGAN, KEVIN M Translational Research in the Dystrophinopathies UNIVERSITY OF UTAH$ 1,137,965 5R01NS043349-03 Nishina, Patsy M. Molecular Genetics of Muscular/Neurosensory JACKSON LABORATORY$ 96,781 Models 5R01NS044211-02 SEALOCK, ROBERT W Rescue Analysis of Utrophin & NMJ Support by Syntrophin UNIVERSITY OF NORTH CAROLINA $ 303,863 CHAPEL HILL 5R01NS045979-02 MCARDLE, JOSEPH J Ion Channels and Chemicals Controlling Synapse Stability UNIV OF MED/DENT NJ NEWARK$ 35,892

5R01NS047584-02 TUPLER, ROSSELLA G Investigating the Molecular Basis of FSHD UNIV OF MASSACHUSETTS MED $ 367,688 SCH WORCESTER 5R01NS047726-02 MC NALLY, ELIZABETH M Myoferlin in Muscle Membrane Fusion and Repair UNIVERSITY OF CHICAGO$ 357,400 5R01NS047918-07 HINTON, VERONICA J Cognitive Genetic Aspects of Duchenne Muscular COLUMBIA UNIVERSITY HEALTH $ 388,313 Dystrophy SCIENCES 5R21NS046342-02 WORMAN, HOWARD J DUX4 and Facioscapulohumeral Muscular COLUMBIA UNIVERSITY HEALTH $ 156,453 Dystrophy SCIENCES 5R44NS045432-03 MCQUILLAN, DAVID J Biglycan as a Therapeutic for Muscular Dystrophy LIFECELL CORPORATION$ 548,725 5T32NS007495-03 SCHOR, NINA F Childhood Neurodevelopmental and Degenerative Disease CHILDREN'S HOSP PITTSBURGH/UPMC $ 242,230 HLTH SYS 5U13NS043180-03 SANGER, TERENCE D NIH Task Force on Childhood Motor Disorders STANFORD UNIVERSITY$ 12,500 5U54NS048843-02** MOXLEY, RICHARD T Muscular Dystrophy Cooperative Research UNIVERSITY OF ROCHESTER$ 1,462,151 Center 5U54RR019482-02 GRIGGS, ROBERT C Nervous System Channelopathies: Pathogenesis & UNIVERSITY OF ROCHESTER$ 25,000 Treatment 5Z01NS002038-30 Dalakas, Marinos Combined Clinical, Viral And Immunological Studies In $ 910,125 Neuromuscular Diseases 5Z01NS002973-06 Goldfarb, Lev Genotype-phenotype Correlations In Movement And $ 282,970 Neuromuscular Disorders 5Z01NS002974-06 Fischbeck, Kenneth Studies Of Hereditary Neurological Disease$ 540,579 7R01NS035071-08 EPSTEIN, HENRY F. Interactions of Myotonic Dystrophy Protein Kinase UNIVERSITY OF TEXAS MEDICAL BR $ 339,750 GALVESTON N01AR002250 DM and FSHD Registry Rochester University $ 200,000 Total $ 14,756,290 ** Moxley grant amount coded as FSHD is $365,538 The FSH Society has funded $1,245,212.84 for FSHD research to date! Please help us continue the work by sending in your donation today. We can’t do it without all of you! 28 FSH WATCH NEWSLETTER SUMMER 2005 History of the MD-CARE Act A Federal Advisory Committee: The Muscular Dystrophy Coordinating Committee The members of the fifteen member MDCC committee and the Executive Sec- The “Muscular Dystrophy Assistance, Coordinating Committee established retary of the MDCC at present are: Duane Research and Education Ammendments of under section 6 of the MD-CARE Act.” F. Alexander, M.D., Director, DHHS NIH 2001” (MD-CARE Act), Public Law 107- The Act calls for “Centers of Excellence” NICHD; Colonel Kenneth Bertram, M.D., 84, signed on December 18, 2001, man- and for the NIH to award grants and con- Ph.D., FACP, Director, Congressionally dated the establishment of the Muscular tracts … to public or nonprofit private Directed Medical Research Programs, US Dystrophy Coordinating Committee entities to pay all or part of the cost of Army Research and Materiel Command, (MDCC), to coordinate activities across planning, establishing, improving, and pro- DoD; Jose F. Cordero, M.D., M.P.H., Assis- the DHHS, NIH, NINDS, NIAMS, viding basic operating support for centers tant Surgeon General, U.S. Public Health NICHD, and the other national research of excellence regarding research on various Service, Director, National Center For institutes, as appropriate, and with other forms of MD.” Birth Defects and Developmental Disabili- Federal health programs and activities Furthermore, due to insightful rework- ties, Centers for Disease Control and Pre- relating to the various forms of MD. The ing of the draft of the law, the law also vention; Donavon R. Decker, Patient Act specifically charges the MDCC with stipulates that the CRCs “shall supplement Advocate (LGMD); Mary Jean Duckett, responsibility to develop a plan for con- but not replace the establishment of a Acting Deputy Director, Disabled and ducting and supporting research and edu- comprehensive research portfolio in all the Elderly Health Programs Group, Centers cation on MD through the national muscular dystrophies. As a whole, the cen- for Medicare and Medicaid Services, research institutes, and to periodically ters shall conduct basic and clinical DHHS; Patricia A. Furlong, President, review and revise the plan. research in all forms of MD including early Parent Project Muscular Dystrophy, Public Law 107-84 is an Act: “To detection, diagnosis, prevention, and treat- Patient Advocate (Duchenne MD); amend the Public Health Service Act to ment, including the fields of muscle biolo- Sharon E. Hesterlee, Ph.D., Director, provide for research with respect to vari- gy, genetics, noninvasive imaging, genetics, Research Development, Muscular Dystro- ous forms of MD, including Duchenne, pharmacological and other therapies.” phy Association, Patient/Professional Becker, LG, congenital, FSHD, myotonic, The Act requires the Secretary of the Advocate (MDAUSA); Russell G. Katz, oculopharyngeal, distal, and Emery-Drei- DHHS, Tommy G. Thompson in our case, M.D., Director, Division of Neuropharma- fuss muscular dystrophies. Be it enacted by to establish the MDCC to coordinate cological Drug Products, Office of Drug the Senate and House of Representatives research, programs and other “activities Evaluation 1, Center for Drug Evaluation of the United States of America in Con- across the National Institutes and with and Research, Food and Drug Administra- gress assembled, Muscular Dystrophy other Federal health programs and activi- tion; Stephen I. Katz, M.D., Ph.D., Chair, Community Assistance, Research and ties relating to the various forms of MD.” MDCC, Director, DHHS NIH NIAMS; Education Amendments of 2001. This Act The MDCC consists of 15 members Story C. Landis, Ph.D., Director, DHHS may be cited as the ‘Muscular Dystrophy appointed by the Secretary and vetted by NIH NINDS; Merle McPherson, M.D., Community Assistance, Research and the White House liaison committee. The M.P.H., Director, Division of Services for Education Amendments of 2001,’ or the MD-CARE Act calls for two-thirds, or ten Children with Special Health Needs, ‘MD-CARE Act’”. members of the MDCC to represent gov- Maternal and Child Health Bureau, In the MD-CARE Act 2001, Congress ernmental agencies, including the direc- Health Resources and Services Adminis- requests of the NIH initiatives and tors or their designees of each of the tration, DHHS HRSA; Patricia A. Morris- progress in MD research through the national research institutes involved in sey, Ph.D., Commissioner, Administration Director, Elias Zerhouni, M.D., of the MD research and other agencies that have on Developmental Disabilities, Adminis- NIH. The Act calls for “expansion, inten- programs involving health functions or tration for Children and Families, DHHS; sification, and coordination of activities. In responsibilities relevant to dystrophy. This DOE – Vacancy; Daniel Paul Perez, Presi- general, the Director of NIH, in coordina- includes the federal agencies of the CDC, dent and Chief Executive Officer, FSH tion with the Directors of the NINDS, the HRSA and the FDA and representa- Society, Inc., Patient Advocate FSHD; NIAMS, NICHD, and the other national tives of other governmental agencies that Bradley R. Stephenson, Patient Advocate research institutes as appropriate, shall serve children with MD, such as the DOE. (Becker MD); and, John D. Porter, Ph.D., expand and intensify programs of such When the law was in draft form it was Executive Secretary, MDCC, Program Institutes with respect to research and requested by the FSH Society that the Director, DHHS NIH NINDS. related activities concerning various forms addition be made to add the other one- The MD-CARE Act 2001 states that of MD, including Duchenne, myotonic, third or five members of the MDCC be no later than one year after the date of FSHD and other forms of MD.” public members, “including a broad cross- enactment of the law that the MDCC The Act clarifies that this is to be done section of persons affected with muscular should have developed a plan for conduct- using a committee to help with coordina- dystrophies including parents or legal ing and supporting research and education tion. “The Directors referred to [above] guardians, affected individuals, on MD through all listed federal agencies. shall jointly coordinate the programs researchers, and clinicians.” The members The MDCC is also charged with periodi- referred to in such paragraph and consult of the MDCC serve for three year terms with the Muscular Dystrophy Interagency and may be reappointed. continued on page 29 FSH WATCH NEWSLETTER SUMMER 2005 29

History of the MD-CARE Act, continued from page 28 cally reviewing and revising the plan. which was submitted to Congress in Prof. David Housman, Chair of the FSH The law requests the plan to “1. pro- August 2004. Next steps for the commit- Society’s SAB presented FSHD research vide for a broad range of research and edu- tee include an analysis of existing activities needs and directions. cation activities relating to biomedical, within the MD community that relate to The initial stage of assembling the epidemiological, psychosocial, and rehabil- specific goals of the plan and refining the research plan included an assessment of itative issues, including studies of the plan to identify more specific research gaps the current research efforts in MD. Infor- impact of such diseases in rural and under- and needs. mation was assembled on projects and pro- served communities; 2. identify priorities On July 1, 2003 the first meeting of grams funded by the NIH and non-NIH among the programs and activities of the the MDCC was convened. This meeting funding of MD research from private NIH regarding such diseases; and, 3. was the only MDCC meeting held in the health advocacy organizations and other reflect input from a broad range of scien- federal fiscal year 2003. The committee government agencies. tists, patients, and advocacy groups.” defined the process of how to develop a The first meeting of the NIH Specifically the law requires the plan research and education plan for NIH. The MDRWG was held on October 8 and 9, provide for the following for each form of NIH proposed that the plan be developed 2003, in Bethesda, Maryland, and includ- MD: “1. research to determine the reasons in a manner similar to previous planning ed about a dozen extramural researchers, underlying the incidence and prevalence processes and reviewed three other previ- scientific staff from the DoD’s research of various forms of MD; 2. basic research ous examples of plans. The three were: the program, the CDC, and several NIH insti- concerning the etiology and genetic links Parkinson’s Disease Matrix, the “Bench- tutes; in addition to NINDS, NIAMS and of the disease and potential causes of marks” for Epilepsy Research, and the NICHD, the MDCC cited the NHLBI, the mutations; 3. development of improved Report of the Brain Tumor Progress ORD, the NHGRI, and the NCRR as screening techniques; 4. basic and clinical Review Group. There was a desire to important invitees to the MD research research for the development and evalua- define the elements using a risk versus plan drafting meeting. tion of new treatments, including new bio- time matrix format, which was used for The second meeting of the DHHS logical agents; and 5. information and the overall Director of NIH, Dr. Elias Zer- NIH MDCC was held on March 22, 2004. education programs for health care profes- houni’s, Parkinson’s Disease Summit in This meeting was the only MDCC meeting sionals and the public.” July 2002. held in the federal fiscal year 2004. A web- Additionally, the MDCC must report The July 1, 2003 meeting agenda can site was setup for the MDCC containing to Congress [Committee on Energy and be found at internet web site: information on meetings, agendas, min- Commerce of the House of Representa- http://www.ninds.nih.gov/find_people/ utes, committee information, and future tives, and the Committee on Health, Edu- groups/mdcc/index.htm#meeting_agenda task found at internet hyperlink cation, Labor, and Pensions of the Senate] The July 1, 2003 meeting minutes can http://www.ninds.nih.gov/find_people biennially. The report needs to cover be found at internet web site: /groups/mdcc/index.htm research, education, and other activities http://www.ninds.nih.gov/find_people/ and distributed to participants. on MD being conducted or supported groups/mdcc/index.htm#minutes At this meeting the process of develop- through the DHHS. Each such report The MDCC came to a consensus to ing the draft research and education plan needs to describe the plan and revisions to continue to build on the scientific expert- was reviewed. When the MDRWG met in the plan, the amounts spent by DHHS on ise of the prior meetings of the NIH October 2003 to develop the MD research each type of MD (Duchenne, myotonic, MDRTF and their members to draft a plan, some of the areas developed were FSHD, etc.), and the identification of proj- research plan for the NIH institutes, and specific to particular forms of MD, and ects of importance to be considered by the that a newly named working group, which others were common to all forms of MD. national research institutes in MD would include some MDCC members, The goals were revised by the MDRWG research. would begin work on a draft of this scien- and many were broadened. The result was The MD-CARE Act, P.L. 107-84) tific research and education plan. The that the plan did not lend itself to a time- authorized the establishment of the name of this newly formed research work- risk matrix format as many areas had mul- MDCC to coordinate activities across NIH ing group was the NIH MDRWG. Daniel tiple time-risk designations. Therefore, it and with other federal health programs Paul Perez and the FSH Society had been was decided that at a later point in time and activities relevant to the various forms representing FSHD interests on the the MDRWG and the NIH will develop a of MD. The MD-CARE Act directed the MDRTF during the interval between the matrix at the time it develops the imple- committee to develop a plan for conduct- passage of the law and the first meeting of mentation plan. This will also allow for ing and supporting research and education the MDCC which spanned nineteen input from other non-NIH federal agen- on MD through the national research months or three calendar years (December cies. institutes, and to submit this plan to Con- 18, 2001 – July 1, 2003) or two federal fis- The research plan was reviewed in gress within the first year of the establish- cal years (FY2002-2003). Daniel Paul detail at the March 22, 2004 meeting of ment of the MDCC. Perez was removed from the roster of the the MDCC and minutes of the meeting The MDCC has met three times and MDRWG; the MDRTF was a sub-group can be found on the NIH MDCC website. has developed a Muscular Dystrophy reporting to the MDCC on which Daniel The March 22, 2004 meeting agenda Research and Education Plan for NIH, Paul Perez serves. Dr. Rune Frants and continued on page 30 30 FSH WATCH NEWSLETTER SUMMER 2005

History of the MD-CARE Act, continued from page 29 John D. Porter, Ph.D. can be found at internet web site: icant gaps in the diseases of unique patho- Named as the New http://www.ninds.nih.gov/find_people/ physiology e.g. FSHD, EDMD and OPMD. Extramural Program groups/mdcc/march04agenda.htm An update was given on the forthcom- The March 22, 2004 meeting minutes ing Congressionally mandated Burden of Director for MD & FSHD can be found at internet web site: Muscle Disease Conference held on Janu- at DHHS NIH NINDS http://www.ninds.nih.gov/find_people/ ary 26-27, 2005. Last, other federal agen- The NINDS at the DHHS-NIH groups/mdcc/20040322MDCCminutes.htm cies presented their work on MD research - announced a new Program Director for Dr. Katz, the Chair of the MDCC, stat- the CDC presented updates on DMD sur- the Muscular Dystrophies in late 2004. Dr. ed that the plan needed to be submitted to veillance and activities, and MD STARNet John D. Porter should now be contacted Congress in July 2004 and requested Program. The DoD presented its update on for inquiries regarding FSHD grant appli- MDCC members to pay strict attention to recent research on and funding of MD cations at the NIH. Dr. Katrina Gwinn- timelines to ensure the timely delivery of research. At the outset of this meeting, Hardy will be working with Dr. Porter to written materials. The MDCC research Daniel Paul Perez went on record regarding help with the FSHD research portfolio. Dr. plan was sent to the administration and it the heavy emphasis on DMD in the meet- Gwinn-Hardy has done an extraordinary was subsequently approved and sent to the ing agenda and by the federal and national job of increasing the NIH portfolio on U.S. Congress. research agencies to the exclusion of all FSHD research to date and we hope we The July, 2004, 41-page MDCC MD other dystrophies. will continue to have the benefit of her national research plan can be found at The December 1, 2004 meeting agenda knowledge and expertise on FSHD! Dr. internet web site: can be found at internet web site: Porter has also assumed a key and crucial http://www.ninds.nih.gov/find_people/ http://www.ninds.nih.gov/find_people/ role as Executive Secretary on the Federal groups/mdcc/MD_Plan_submitted.pdf groups/mdcc/MeetingAgenda_20041201.htm Advisory Committee, MDCC, mandated The third meeting of the DHHS NIH The December 1, 2004 meeting min- by the MD-CARE Act Law of 2001. MDCC was held on December 1, 2004. utes can be found at internet web site: Dr. Porter is the new Program Director This meeting is the first held in the federal http://www.ninds.nih.gov/find_people/ for NINDS. He is in charge of the extra- fiscal year 2005 (Oct. 1, 2004 – Sept. 30, groups/mdcc/20041201MDCCminutes.htm mural research program in MD and also is 2005). At this meeting the status of imple- FSHD is prominently represented in Executive Secretary for the MDCC, an mentation of the MD research plan was the national research plan. Several key advisory committee designed to coordinate discussed. As well, an update was given by successes were the recognition of FSHD as research and education efforts across the the NIH on activities and new initiatives a unique pathology needing unique empha- federal agencies and non-profit organiza- from NIH. sis and the need for the creation of animal tions with interests in MD. Dr. Porter NIH self-identified eight out of 164 models and biomaterials repositories, as obtained his Ph.D. from the Medical Col- grants and contracts in its portfolio as well as the need for creating therapeutic lege of Virginia in 1980 and has a 20 plus being related to the unique pathology of interventions. year research career in muscle biology, last FSHD. It recognized that there were signif- serving as Professor of Neurology at Case Western Reserve University. He has pub- lished nearly 100 papers and book chapters What is CRISP? in the field of muscle biology, with many CRISP (Computer Retrieval of Information on Scientific Projects) is a searchable data- over the last 10 years in the MD field. He base of federally funded biomedical research projects conducted at universities, hospitals, chose to leave his well-funded and produc- and other research institutions. The database, maintained by the Office of Extramural tive research lab to join the extramural Research at the NIH, includes projects funded by the NIH, SAMHSA, FDA, CDCP, program staff at NINDS because of the AHRQ, and OASH. Users, including the public, can use the CRISP interface to search for challenges and opportunities offered by the scientific concepts, emerging trends and techniques, or to identify specific projects and/or MD-CARE Act and MDCC. investigators. See: http://crisp.cit.nih.gov/ The NIH/NINDS and the MDCC actively offers its assistance in exploring ideas with any FSHD researcher(s) as they relate to FSHD research. Please consider The Combined Federal Campaign for the FSH Society, Inc. contacting Dr. Porter. Dr. Porter would be Federal employees and military personnel can donate to the FSH Society, Inc. through happy to conference call with the CFC. Please consider making a contribution to the FSH Society through the CFC. researcher(s) to explore avenues for sup- The CFC is operated by the United States Government Office of Personnel Manage- port for FSHD research under upcoming ment. The FSH Society, Inc. CFC code is #2662. For more information about the CFC you and existing funding programs/mecha- may visit the OPM website at http://www.opm.gov/cfc/index.htm nisms. The FSH Society hopes that you will take the time to contact Dr. Porter to Your generosity ensures the continued work of the FSH Society. introduce yourselves and to familiarize Dr. Please consider making a tax-deductible donation today! continued on page 31 FSH WATCH NEWSLETTER SUMMER 2005 31

Porter, continued from page 30 Update on Clinical Trial of Albuterol and Oxandrolone Porter with research directions and ques- Trials and Tribulations FDA Office of Orphan Products Develop- tions in need of answers in the field of Although research on medications that ment. The purpose of the study as FSHD. Last, the Society hopes you will may improve FSHD is critical, bringing the described on the web site extend heartfelt thanks to Dr. Gwinn- various interests together (researchers, http://www.clinicaltrials.gov/ct/show/ Hardy for the excellent gains made in government funding and pharmaceutical NCT00027391?order=1 was: FSHD research and to continue to keep “to determine whether Albuterol or Dr. Gwinn-Hardy informed on FSHD companies) can be daunting. Still, the Oxandrolone, alone or in combination, are issues as appropriate. FSH Society is committed to facilitating these clinical trials. Recently we worked able to increase strength and muscle mass Contact: extensively to get a much-anticipated trial in patients with FSHD. It also will deter- John D. Porter, Ph.D., Program Director, of Albuterol and Oxandrolone to take mine if Albuterol given in ‘pulsed’ fashion Neuromuscular Disease place. Unfortunately the efforts of the will have more effect than when given Executive Secretary, MDCC Channels, Society and researchers were unsuccessful. continuously.” The treatment or interven- Synapses, and Circuits Cluster We would like to offer the following histo- tion was described as type “drug.” The NINDS, NIH ry of this struggle to illustrate the inner study design was: “Treatment, Randomized, 6001 Executive Blvd workings of research. Although the Society Double-Blind, Placebo Control, Efficacy NINDS/NSC 2142 is obviously disappointed, we are commit- Study.” The initial start date was Septem- Bethesda MD 20892 USA ted to continuing the fight for this, and ber 2001 with an expected completion (301) 496-1917 other, research on FSHD. date of August 2004. One hundred and (301) 402-1501 sixty patients were to have been enrolled [email protected] The clinical trials study of Albuterol and Oxandrolone in patients with FSHD and randomized to one of four groups: placebo, pulsed Albuterol, Oxandrolone, Keep up the excellent work! will not take place as planned. The study was originally sponsored and funded by the or both pulsed Albuterol and Oxan- drolone. Treatment was to continue for 52 NIH MD Program Staff Info weeks unless unacceptable side effects occurred. Patients were to have undergone A consistent comment that we have heard from the NIH over the past 13 years is testing of muscle function. All patients that it does not receive enough grant, research, clinical and fellowship applications for were to have returned for follow-up assess- FSHD. The FSH Society repeatedly has stated that the NIH could take more steps to recruit research and request applications and needs to do more in this area. To help with ments at weeks four, 12, 26, and 52. Ages matters, The FSH Society would like to highlight the scientific and research contacts at 18 to 80 years of both genders were eligi- the top four U.S. NIH institutes working on FSHD, and encourage researchers, clini- ble for the trial. cians, graduate students and other agencies to contact them to discuss fellowship and The inclusion criteria as listed on the grant opportunities to bring FSHD research funding to the next level. The NIH MD clincialtrials.gov internet site were: “pres- program directors and Scientific/Research Contacts at NIAMS, NINDS, NICHD, and ence of 4q35 ‘small fragment’ of less than NHLBI are: 40 kb by standard DNA testing; weakness of the facial muscles, including frontalis, Glen H. Nuckolls, Ph.D., Director, Muscle Disorders and Therapies Program orbicularis oculi, or orbicularis oris; weak- Muscle Biology Branch, NIAMS ness of scapular stabilizers or foot dorsi- 6701 Democracy Boulevard, Suite 800, Bethesda, MD 20892-4872 flexors; ambulatory; and weakness grade 2 (301) 594-5128; Email: [email protected] or worse in the arm using upper extremity grading scale.” The exclusion criteria from John Porter, Ph.D., Program Director, Neuromuscular Disease the same internet page were: “prior use of Channels, Synapses, and Circuits Cluster NINDS 6001 Executive Boulevard, Room 2142, MSC 9523, Bethesda, MD 20892-9523 oral beta-2 agonists for a period of at least (301) 496-1917; FAX: (301) 402-1501; Email: [email protected] one year or within the past three months; concurrent use of other sympathomimetic Mary Lou Oster-Granite, Ph.D., Chief, agents, antidepressants, or beta-2 receptor Mental Retardation and Developmental Disabilities Branch NICHD blockers; pregnancy; known hypersensitivi- 6100 Executive Boulevard, Room 4B09G, MSC 7510, Bethesda, MD 20892-7510 ty to anabolic steroids; any medical or psy- (301) 435-6866 Fax: 301-496-3791; Email: [email protected] chological condition that would interfere with the study; requirement for a wheel- John Fakunding, Ph.D. chair.” Director, Heart Research Program, Division of Heart and Vascular Diseases NHLBI The principal investigator of the trial 6701 Rockledge Drive, Room 9170, MSC 7940, Bethesda, MD 20892-7940 (301) 435-0494; Fax: (301) 480-1336; Email: [email protected] continued on page 32 32 FSH WATCH NEWSLETTER SUMMER 2005

Albuterol and Oxandrolone, continued from page 31 was John T. Kissel, M.D., Ohio State Uni- Historically, Oxandrolone is a generic orphan drug laws designed to help versity Medical Center, Columbus, Ohio, drug that was approved by the FDA in the patients, BTGC received seven years of 43210. Study ID Numbers: FD-R-2029- early 1960's and all patents on it had market exclusivity post approval. This 01; FD-R-002029-01. expired. Until 1989, the drug was sold price has achieved an extraordinary mark- This three year study was funded in and manufactured by Searle Laboratories up on the regular market of what was once 2001 for a total of $750,000 ($250,000 per under the trade name Anavar and by SPA an inexpensive drug. annum) from the FDA and with the MDA Labs in Europe under the names Lipidex, Savient requested all the money for funding approximately $300,000. In June Antitriol, or Lonavar. The drug was dis- the Oxandrin™ to be paid up front for the 2003, we reported that the start of the continued in 1989 due in part to contro- FSHD clinical trials because the patent clinical trial of Albuterol and Oxan- versial illegal use by bodybuilders favoring would expire, generic Oxandrolone would drolone in FSHD being performed by the the drug’s good results and low toxicity. be back on the market, and several ingre- Myopathy Study Group was delayed due to New Jersey-based BTGC and Searle dient manufacturers were producing large the unavailability of the long-acting entered an agreement regarding the drug quantities of the drug. The generic price Albuterol preparation to be used in the in late 1995 and subsequently BTGC (now would substantially undercut Savient and study. The manufacture of Albuterol was known as Savient) announced the U.S. it could lose 80-90% of Oxandrin™ sales. suspended by the FDA for quality reasons. drug launch of Oxandrin™. When this occurred, the price of generic Subsequently, two companies were unsuc- Typically, it should be available as a Oxandrolone, and availability of new long- cessful in bringing the Albuterol to mar- generic, but BTGC was able to gain exclu- lasting Albuterol, would make the trial ket. Finally, a third company, Odyssey sivity for distributing the drug because of cost effective. Pharmaceuticals, Inc. began distributing AIDS wasting indications and were grant- Dr. Kissel informed the MDA and the the needed formulation of Albuterol under ed Orphan Drug designation by the FDA. FSH Society for the need to bridge the gap the trade name VoSpire Extended Orphan Drug designation is for rare dis- of $300,000 to begin the trial. The Society Release™ in February 2004. eases or conditions with a prevalence of could not directly fund at that level. The Both the FDA and the MDA allowed less than 200,000 cases in the U.S. Under continued on page 33 for extensions of their grants given the dif- ficulties acquiring Albuterol. When Dr. Kissel informed Savient van der Maarel and Frants Publish Article in AJHG Pharmaceuticals (formerly the Bio-Tech- The continuous efforts of the FSH Society, alongside the FSHD research community nology General Corporation - BTGC) that to put FSHD on the map are becoming increasingly effective. Drs. Rune Frants and Sil- they were ready to begin the trial, Savient vere van der Maarel recently wrote a review on FSHD for The American Journal of Pharmaceuticals responded that they were Human Genetics which is now published in Volume 76, Number 3 March 2005. no longer able to provide Oxandrolone at The deputy editor of The American Journal of Human Genetics, Kathryn Garber, no cost for research purposes. Savient writes in that month’s journal: “Fascioscapulohumeral MD is a progressive disorder char- Pharmaceuticals did not have the needed acterized by muscle weakness and wasting that generally starts in the upper body and drug dosage and matching placebo cap- that can be asymmetric. Contractions of a chromosome 4q subtelomeric repeat, called sules. However, they would provide the ‘D4Z4,’ cause FSHD, but the mechanism by which this happens is not fully understood. drug at market rate which was approxi- This month in the Journal, van der Maarel and Frants give us a window into the com- plexity of this problem. It involves two alleles of the 4q subtelomeric region and a highly mately $800,000 - almost as much as the homologous repeat on chromosome 10qter, but contractions in only one of these three budget for the entire study. Dr. Kissel sequences are found in persons with FSHD. It is likely that the D4Z4 contraction alters attempted to reduce the cost of Oxan- the transcriptional control of other genes and that this leads to the FSHD phenotype. drolone. There are several models for how this occurs; van der Maarel and Frants discuss the evi- At the request of Drs. Jerry Mendell, dence for each.” Robert Griggs and John Kissel, the FSH The article is an excellent review and description of current FSHD and related Society contacted Dr. Sim Fass, Chairman research and shows the extraordinary progress that the FSH Society research fellowship of the Board of BTGC/Savient Pharma- program and the FSHD research community has helped to bring about in a short period ceuticals to help negotiate a reduction in of five years. the charges for Oxandrin™ in the Oxan- Please consider distributing the reference to this article to individuals who might drin™/Albuterol trial. The FSH Society wish to become newly engaged in FSHD research as well as those in a position to peer- negotiated a $500,000 discount through review, fund and judge work on FSHD. extensive discussion with Dr. Sim Fass, Review article: The D4Z4 Repeat–Mediated Pathogenesis of Facioscapulohumeral Muscu- Chris Clement, President & CEO, and lar Dystrophy, Silvère M. van der Maarel and Rune R. American Journal of Human Genetics. Volume 76:375-386, Number 3 March 2005 Savient’s Research Director, Zeb Horowitz. http://www.journals.uchicago.edu/AJHG/journal/contents/v76n3.html FSH WATCH NEWSLETTER SUMMER 2005 33

Albuterol and Oxandrolone, continued from page 32 First Medical Textbook MDA was constrained by grants proce- quent randomized, double-blind, placebo- on FSHD Published dures and protocol and had begun to controlled trial no improvement of “FSHD Clinical Medicine and request the return of unexpended funds strength, expressed as a composite MVIC Molecular Cell Biology” from previous years. At the suggestion of score derived from the MVIC values of Edited by: Meena Upadhyaya the MDA, Dr. Kissel contacted several multiple muscle groups, could be detected & David N. Cooper generous donors (FSHD patients) from after one year of treatment. The positive FSHD is a unique dominantly inherit- ed disorder of skeletal muscle. FSHD, as Texas and California who had the effect on some secondary outcomes one of the most frequently encountered resources to support the trial when the (strength measures and lean body mass) muscular dystrophies of adult life, has long FDA told Dr. Kissel they could no longer after one year led to the hypothesis that deserved a book specifically devoted to it. keep the extension open. the anabolic effects of Albuterol probably This volume on FSHD is invaluable since, Though Dr. Kissel had put forth an wear off with prolonged use, due to down- in the absence of a single comprehensive enormous effiort to make this trial succeed regulation of b2-receptors. The improve- source, it is often difficult for clinicians and ran into numerous unforeseen difficul- ment in muscle strength and muscle mass and scientists involved with this disorder ties, he is very positive about resubmitting after six months of exposure to Albuterol to obtain a clear and balanced account of grants for a future study. At present he is in our study confirms the short term ana- the many different aspects of this disorder. awaiting the availablity of generic Oxan- bolic effect, but does not preclude a long More than 14 years have elapsed since the drolone. The MDA and the FDA have term effect.” locus for FSHD was mapped to the long stated that both would be very positive The first Albuterol clinical trial was arm of chromosome 4, and 12 years since the identification of the chromosomal and open to receiving a new grant applica- published by Drs. Kissel and Tawil e.g. deletion at 4q35. However, despite many tion with a modified and updated budget Neurology. 2001 Oct 23; 57(8):1434-40. recent advances in this field, the true for the clinical trials. “Randomized, double-blind, placebo-con- identity of the FSHD gene(s) remains elu- At the same time, while the Albuterol/ trolled trial of Albuterol in FSHD” by Kissel sive. The complex biology associated with Oxandrolone trial was stalled in the US, JT, McDermott MP, Mendell JR, King the disease has led to the realization that Albuterol was tested in The Netherlands. WM, Pandya S, Griggs RC, Tawil R; FSH- FSHD, as an apparent disorder of muscle The Neuromuscular Center Nijmegen, DY Group through the Department of gene de-repression, would appear to exem- University Medical Center Nijmegen, Neurology, The Ohio State University, plify an entirely novel pathological mecha- recently published the results in Neurolo- Columbus, 43210, USA. nism. gy. 2004 Aug 24;63(4):702-8, of their The two trials have more similarities The contents of this volume comprise Dutch Albuterol study “Strength training than differences. The Dutch found a all the main strands of current work, with and Albuterol in FSHD” [van der Kooi EL, slightly more positive effect, because they all the key workers across the world con- tributing to it. The varied contributions Vogels OJ, van Asseldonk RJ, Lindeman E, tested Albuterol after six months of use from an international panel on FSHD Hendriks JC, Wohlgemuth M, van der instead of one year of use as in the U.S. cover as many different aspects of FSHD Maarel SM, Padberg GW]. This is the sec- clinical trial. The loss or wearing-off of as possible. ond Albuterol trial or study to reach publi- the positive effect of the drug was probably Chapter 1 provides a comprehensive cation. not completed after these six months. introduction to the FSHD. Chapter 2 cov- The online PubMed abstract from the Another explanation for the difference is ers the detailed historical background. second clinical trial by the Dutch reads: that the Dutch did not use a composite Chapter 3 delineates comprehensive cov- “After the open-label pilot trial in 15 score, but evaluated individual muscle erage of clinical features of FSHD. Chap- FSHD patients The FSH-DY group report- groups in data collection. Short term use ter 4 reports mapping of the FSHD gene ed a significant increase in muscle strength of Albuterol is shown to have benefit in and the discovery of the pathognomonic and mass when given Albuterol (SR, 16.0 FSHD in both trials. deletion which involved the characteristic mg/day) for three months. In the subse- D4Z4 repeats. Chapter 5 deals with the identification and characterization of the genes in the FSHD candidate region. Chapter 6 describes D4Z4-related sequences in the human genome and the Your contribution to the FSH Society is tax-deductible conservation of D4Z4 in other organisms. Chapter 7 covers subtelomeric exchanges and ensures the on-going work of YOUR advocacy group. between 4q and 10q sequences. Chapter 8 outlines genomic analysis of the subtelom- We need your continued support. eric regions of human chromosomes 10q Please send your donation now. and 4q and their relevance to FSHD. Chapter 9 gives an comprehensive account The donation form can be found on the back page. continued on page 34 34 FSH WATCH NEWSLETTER SUMMER 2005

FSHD Textbook, cont. from pg. 33 FSHD: Chromatin Structure, Looping, & Expression of the relevance of the DUX gene family Estimated project total $1,484,705 10. Much evidence suggests that a short to FSHD. Chapter 10 discusses the possi- On September 1, 2004 the DHHS, D4Z4 array on chromosome 4 causes ble mechanisms underlying FSHD. Chap- NIH, NINDS awarded the grant number: FSHD by abnormally altering expression of ter 11 describes known genotype- 1R01NS048859-01 to Melanie Ehrlich, a rather distant gene at 4q35. phenotype relationships in FSHD. Chapter Ph.D. and past FSH Society fellow of “This research involves analyzing the 12 gives an account of germline and Tulane University of Louisiana, New nature of the chromatin and chromatin somatic mutations in FSHD. Chapter 13 Orleans, LA, for the five year period: Sep- proteins in the D4Z4 arrays and in 4q35 explores whether retinal vascular abnor- tember 1, 2004 - April 30, 2009. The proj- gene regions and looking for long-distance malities in FSHD could provide clues for ect title is: FSHD: Chromatin Structure, looping interactions between the array and FSHD pathogenesis. Chapter 14 includes Looping, & Expression. Dr. Ehrlich received promoter regions of candidate FSHD unusual clinical features associated with a NIH grant for $296,941 per year (fiscal genes as well as between the ends of the FSHD. An account of molecular diagnos- year 2004) starting in September 2004 and array. The cells to be analyzed will be tic approaches of FSHD is given in Chap- ending in April 2009. The research is diploid myoblasts, myotubes induced from ter 15. Chapter 16 gives a detailed funded by the NIH NINDS institute. myoblasts, and heterologous cell types, account of in vitro studies of FSHD The description on the NIH CRISP namely, lymphoblastoid cell lines and myoblasts. Chapter 17 explores hypotheses database web site as provided by Dr. diploid fibroblasts. The cultures will be relating to molecular aetiology of FSHD. Ehrlich is: “FSHD is a unique disorder derived from FSHD patient samples, Chapter 18 outlines histological, immuno- involving shortening of an array of tandem which will continue to be collected during logical, molecular and ultrastructural char- 3.3 kb repeats. Unaffected individuals this study, as well as from disease-controls; acteristics of FSHD muscle. Chapter 19 have 11-100 copies of this repeat, D4Z4, the known sizes of their D4Z4 arrays will provides evidence of linkage in a non- at both allelic subtelomeric regions on the be compared to the properties of chro- chromosome 4-linked family. Chapter 20 long arm of chromosome 4 (at 4q35). matin at 4q35. outlines gender differences in the expres- Patients afflicted with this progressive, “In vivo DNasel and dimethyl sulfate sion of FSHD. Chapter 21 focuses on debilitating and painful disease have only footprinting, electrophoretic mobility shift genetic counselling for FSHD. Chapter 22 1-10 copies of the repeat on one of their assays, chromatin immunoprecipitation presents information on the alteration of chromosome 4 homologues. assays, immunocytochemistry, and two the sarcolemma in FSHD muscle. Chapter “Almost identical arrays of D4Z4 new assays developed to monitor long- 23 delineates expression of profiling exper- repeats embedded in extremely similar range chromatin interactions will be the iments in FSHD myoblasts. Finally, Chap- sequences on both sides of the array for main techniques used in this study. The ter 24 gives an account of therapeutic 25-45 kb are located at the subtelomeric proposed research should elucidate new trials and the medical management in end of the long arm of chromosome 10 but aspects of long-distance control of gene FSHD. The textbook includes an appendix although these also can be present in 1- expression as well as lending clinically use- on the FSH Society. This book was 100 copies, there is no phenotype associat- ful insights into this currently intractable launched in April, 2004. ed with short D4Z4 arrays on chromosome disease.”

To order: Customer Services for credit card orders: FSHD International Research Consortium Telephone orders: +44 (0) 1264 343071 Research Workshop, Toronto, Canada Fax: +44 (0) 1235 829011 Email: [email protected] Web: www.garlandscience.com BIOS Scientific Publishers ISBN:1859962440 Pub Date: June 15, 2004 Type: Hardback Book Price: $149.00 Extent: 250 pages The FSHD IRC Research Workshop institutes of the NIH, the Canadian Insti- In East and South-East Asia: was held on October 26, 2004 in Toronto, tutes of Health Research and MDC. Taylor and Francis Asia Pacific Canada. The meeting chair was Silvère The workshop format was comprised of 240 MacPherson Road van der Maarel, Ph.D. and the meeting oral platform presentations and interactive #08-01 Pines Industrial Building was co-organized by Daniel Paul Perez, poster sessions complemented by active Singapore 348574 FSH Society. discussion and problem solving. To formu- Outside East and South-East Asia: This meeting of the FSHD IRC was late better future research strategies for the Garland Science/ organized with the support of the FSH FSHD field, the final session focused on BIOS Scientific Publishers Society, the MDAUSA and the Association four issues that were raised during the 4 Park Square Française Contre les Myopathies. We were workshop held in 2003. Each of those Milton Park, Oxfordshire honored to have several directors, program issues addresses the interface of basic OX14 4RN, UK directors and senior staff from multiple continued on page 35 FSH WATCH NEWSLETTER SUMMER 2005 35

Workshop, cont. from page 34 Richard J.L.F. Lemmers, Ph.D., “Timing NIAMS, NINDS or NICHD and each of molecular research and the clinic. Open- and mechanism of somatic D4Z4 contrac- other institutes accepting applications for ing remarks were given by Daniel Paul tions; causes and consequences.” (Molecular this award. (See PA-05-051 on page 19.) Perez, President & CEO, FSH Society, Inc. genetics testing in FSHD.) The third series of lectures on proteins The first series of lectures were on Denise A. Figlewicz, Ph.D., “Withdraw- involved in FSHD was moderated by models systems in FSHD moderated by al from the cell cycle in FSHD myoblasts.” Denise Figlewicz, Ph.D., which covered Silvère van der Maarel, Ph.D. Valery Kazakov, M.D., Ph.D., “What is research on the “Functional study of the Sabrina Sacconi, Ph.D. presented a Scapuloperoneal or (Facio)scapuloperoneal DUX4 and DUX4c genes.” lecture pertaining to possible therapeutic Muscular Dystrophy with 4q35 deletion: Is it Silvère M. van der Maarel, Ph.D., “The avenues titled “Myoblasts from unaffected an independent form or a variant of a FSHD? interaction between FRG1P and PABPN1 muscle of FSHD patients demonstrate no What was Davidenkov’s opinion concerning implies a common molecular pathway for the alteration in proliferation, differentiation and this important problem?” muscular dystrophies FSHD and OPMD.” in vivo regenerating ability when compared to After the poster session, the group Dalila Laoudj-Chenivesse, Ph.D., controls.” heard presentations on the NIH initiatives “Increased levels of ANT1 protein and Jane E. Hewitt, Ph.D. presented a from Glen H. Nuckolls, Ph.D.; and the response to oxidative stress are early events in remarkable finding that the D4Z4 section NIH FSHD National Registry at the Uni- FSHD muscle.” of repeats has a homologue in mouse in a versity of Rochester from Rabi Tawil, Sara Winokur, Ph.D., “Characterization lecture titled “Identification of homologues of M.D.. of CP39, a candidate gene for FSHD.” the D4Z4 repeat.” Dr. Glen Nuckolls discussed funding Finally, the discussion and closure Rossella Tupler, M.D., Ph.D. presented opportunities in FSHD disease research focused on the general topic “From an on the results of the development of a from the NIH DHHS. He spoke to the inventory to work plan: A pragmatic transgenic mouse for FSHD in a lecture research community about NIH funding approach of four issues at the interface of titled “Analysis of 4q35 gene over-expression opportunities called Program Announce- basic molecular research and the clinic.” in transgenic mice.” ments that were forthcoming. The first is Four questions were presented for discus- The second set of lectures was on titled “Muscular Dystrophy: Pathogenesis and sion to create consensus and action plan. genetic mechanisms in FSHD, and was Therapies” and it will cover basic, transla- The first question was, “The role of moderated by Sara Winokur, Ph.D. tional or clinical research on any form of ANT1 in the FSHD phenotype - Can we Melanie Ehrlich, Ph.D., “Analysis of the MD. Research Project Grant Awards relate a mitochondrial dysfunction to com- D4Z4 repeat array with a highly specific (R01) are up to $499,999 direct costs/year plaints of fatigue and pain? Which issues need hybridization probe.” for up to 5 years. Exploratory/Develop- to be addressed and how?” Moderated by Kristen Bastress, Ph.D. and Marcy mental Research Grant Awards (R21) up Jane E. Hewitt, Ph.D. Speer, Ph.D., “D4Z4 fragment analysis and to $275,000 over two years. Both are open The second question was, “Muscle genome-wide SNP screening in non-chromo- to domestic (U.S.) or foreign (non-U.S.) specificity of the disease - myoblasts from some 4-linked FSHD.” institutions and are available from four affected and non-affected tissue seem to have Yi-Wen Chen, Ph.D., “Over-expression institutes at the NIH by applying to the different phenotypic properties. Which issues of Pitx1 gene activates muscle atrophy path- NIAMS, NINDS, NICHD or NHLBI. (See need to be addressed and how?” Moderated ways.” PA-05-038 on page 19.) by George W.A.M. Padberg, M.D., Ph.D. Poster sessions included several Dr. Nuckolls spoke about muscle dis- The third question was, “Population groundbreaking papers and findings for ease research training fellowships that genetics - mostly based on non-published data, 2004. Some of the posters were well recog- would be forthcoming for Predoctoral there may be population differences in the nized by their publication in top quality (award mechanism type F31), Postdoctoral occurrence and/or susceptibility to the disease. peer-reviewed journals. Emphasis was (award mechanism type F32) or Senior What is the relevance? Which issues need to placed on the newest data; for example, Fellows (award mechanism F33) available be addressed and how?” Moderated by Sil- the finding that there are two types of for U.S. citizens or permanent residents. vère M. van der Maarel, Ph.D. telomeres on 4q35 and only one causes Fellowship grant applications are with the The fourth and final question for dis- FSHD (this is also known as the 4q35 A NIAMS, NINDS or NICHD and each of cussion was “Unusual phenotypes and geno- and B allele). Following is a list of presen- the institutes may not accept applications types - over the last years, we have seen ters and their work: for all of the fellowship types. (See PA-05- publications of unusual phenotypes and geno- Silvere M. van der Maarel, Ph.D., 052 on page 19.) types in FSHD. How can these contribute to “Contractions of D4Z4 on 4qB subtelomeres Last, Dr. Nuckolls spoke of Muscle our understanding of the pathogenesis of do not cause FSHD.” Disease Research Career Development FSHD at large? Which issues need to be Cecilia Östlund, Ph.D., “Intracellular and Mentoring Awards. These are called addressed and how?” Moderated by Peter trafficking and dynamics of double home- the Mentored Basic (K01, K08), Clinical W. Lunt. odomain proteins.” (K23), or Quantitative Researchers (K25), The complete set of abstracts may be Alexandre Ottaviani, Ph.D., “Role of Newly Independent Investigators (K02) or found as an Adobe pdf file on the FSH the D4Z4 sequence, telomere repeats and sub- Midcareer Clinical Investigators (K24). Society internet home page telomeric elements in the etiology of the Available for U.S. Citizens or permanent www.fshsociety.org. FSHD.” residents. And again applications go to 36 FSH WATCH NEWSLETTER SUMMER 2005

— Call for Participation — NIH National Registry Helping Solve Respiratory & Breathing Problems in FSHD! of Myotonic Dystrophy The FSH Society is working to better affect breathing, especially at night while and FSHD Patients and define if there are breathing and ventila- sleeping and lying down. Lung capacity tion problems that are overlooked in the measurements in most doctors offices are Family Members is clinical picture/management of FSHD. typically made in a sitting, and not a lying Enrolling Individuals There are a small number of patients down, position and, thus, the actual meas- By University of Rochester reporting the need for a ventilator, and urements may not be accurate. We wonder The University of Rochester Medical more needing non-invasive ventilation if undetected and untreated respiratory Center has been funded by the NIH to such as Bi-PAP and C-PAP. insufficiency over a period of years leads to establish the National Registry of Due to two very recent deaths at an tiredness, sleep problems, fatigue and a Myotonic Dystrophy and Facioscapulo- untimely age, we begin to wonder if respi- lowering of the quality of life, and even humeral Muscular Dystrophy Patients ratory insufficiency due to respiratory mus- early death. and Family Members. The Registry is a cle weakness is a missing dimension in the Please contact us at the FSH Society if database of patients diagnosed with management of FSHD. The prevalence of you have an interest in this area of myotonic dystrophy or FSHD who are respiratory failure in FSHD is simply not research and would like to be contacted interested in participating in research known. Doctors are not on the lookout for for a research project. We are only collect- about these diseases. Their unaffected breathing problems and related symptoms, ing basic contact information and all infor- family members are also invited to join. To nor are they sensitized to medications that mation is treated as confidential. We will enroll, people are required to complete a may compromise/suppress breathing at send the request from researchers asking comprehensive questionnaire. The Reg- night while patients are asleep. for participation directly from the Society istry assists researchers looking for volun- In July 2004, Drs. Wohlgemuth, Pad- to the registrants. teers willing to participate in their studies berg, et al. published a rare paper on the We hope that this pilot project will by searching the Registry data base for subject in Neurology. 2004 Jul grow into an NIH fundable project in the qualified members. The Registry staff 13;63(1):176-8, titled: “Ventilatory support rehabilitation and the heart, lung and sends those members a letter announcing in FSHD.” The authors state that: “Severe blood institutes. the project. Applications are accepted muscle disease, wheelchair dependency, If you meet the criteria listed above, from members and researchers across the and kyphoscoliosis appeared to be risk fac- please contact the Society at: FSH Society, United States. tors for respiratory failure.” Inc. 3 Westwood Road, Lexington, MA If you would like to participate or have The Society would like to ask for your 02420 USA. Phone: (781) 860-0501, questions regarding the National Registry, help to identify or self-identify patients (781) 862-8422. Fax: (781) 860-0599 please contact: The National Registry of who use ventilatory support or who think e-mail: [email protected], Myotonic Dystrophy and FSHD, 601 Elm- they may have respiratory insufficiency at [email protected], or wood Avenue, Box 673. Rochester, NY night. We are also interested in medica- [email protected]. 14642-8673. Call toll free: (888) 925-4302 tions that patients have found to adversely (9 a.m. to 4 p.m. weekdays, EST). Local (Rochester, NY): (585) 276-0004. Fax: (585) 273-1255. Non-affected Family Members Needed for Research Study ______Dr. Craig McDonald is funded by the National Institute of Disability and Rehabilita- Please tell them you are responding tion Research to search for the effect of health and wellness promotion practices on indi- from a request found in this newsletter. viduals with neuromuscular diseases. Currently, the center is recruiting control subjects Their information is: that are non-affected family members of individuals with FSHD (spouses or relatives) e-mail: between the ages of 18 and 65. [email protected] Volunteers for this study will complete a detailed questionnaire that asks about health web: http://www.dystrophyregistry.org status, physical activity, lifestyle issues, pain, nutrition and diet. Subjects are not required or to travel; the survey will be mailed for completion. Dr. McDonald and his colleagues want http://www.urmc.rochester.edu/ to understand better the factors that contribute to health, wellness and community inte- nihregistry/contact.htm gration in persons with slowly progressing neuromuscular diseases. Participants may receive up to $20 for their time. If you are interested in participating, please contact Ted Abresch at: Ted Abresch, Director of Research Federal employees and military Center for Neuromuscular Disease personnel please consider MED: PM&R, TB 191 University of California, Davis donating to the FSH Society, Davis, CA 95616 Inc. through the CFC #2662. Contact email: [email protected] Contact phone: (530) 752-9085 FSH WATCH NEWSLETTER SUMMER 2005 37

— Call for Participation — Helping Solve Early Onset FSHD and IFSHD! Brain and Tissue Banks for The FSH Society is working with from two groups of subjects described Developmental Disorders researchers who have expressed an interest below. We are only collecting basic contact Enlisting Registered Donors in IFSHD and early onset FSHD. information and all information is treated Researchers have asked for help in defin- as confidential. We will send the request The Brain and Tissue Banks for Devel- ing the phenotype/genotype relations in from researchers asking for participation opmental Disorders at the University of the North American population of directly from the Society to the registrants. Maryland in Baltimore and the University patients with early onset and infantile Please contact us at the FSH Society if of Miami are tissue resources established FSHD. Current data, information and you are or know of a patient or individual to further research aimed at improved anecdotal reports are based mostly on clin- with: understanding, care and treatment of ical observations. There are few systematic 1. clinically defined severe FSHD. This developmental disorders. The Brain and reviews on clinical features of this subset group is defined as patients who report Tissue Banks serve as intermediaries of FSHD. This is rather unfortunate as a needing a wheelchair greater than 50% of between people who wish to have tissue molecular genetic study of this group may the time by age 18 years; or donated for research upon the time of yield great insight into the FSHD mecha- 2. molecularly defined patients who are their death and the researchers who need nism. It is hoped that “clarification of the predicted to have severe FSHD. This this tissue for their vital work. If you are clinical features of these patients will facil- group is defined as patients with EcoRI interested in becoming a registered donor, itate early diagnosis by appropriate symp- fragments smaller than 15kb. This conser- or if you have any questions or concerns tom recognition, and will be a first step vative value will probably identify patients regarding the donation process, please toward defining interventions.” with a milder phenotype in addition to the contact Christine Wade, Project Coordina- FSHD is an autosomal dominant disor- more severe. This corresponds to roughly 3 tor. Thank you for taking the time to con- der caused by deletion within a sub-telom- residual 3.3kb repeats or less. sider the possibilities offered to humanity eric repeat on chromosome 4q35. We hope that this pilot project will through the gift of tissue donation. Inter- Generally speaking in FSHD, there is a grow into an NIH-fundable project. The net site: relationship between the size of the dele- NICHD currently has no grants on FSHD. www.btbank.org tion and disease severity. The larger dele- It is hoped that this pilot project will lead tions, or fewer repeats left between one to bigger and better projects. Similarly, the Christine Wade, Project Coordinator, and nine, are associated with more severe pregnancy study, currently funded by the Brain and Tissue Bank, University of cases of the disease. More severely affected FSH Society, is done so with the hope that Maryland, 655 W. Baltimore Street, BRB individuals are more likely to be sporadic the pilot data will allow the same NIH 10-035, Baltimore, MD USA occurrences (spontaneous or de novo institute dealing with child and maternal (800) 847-1539 or (410) 706-1755 mutations), or born to a parent who is a health to fund a larger project on FSHD. somatic mosaic for the chromosome 4q35 If you meet the criteria listed in 1 or 2 D4Z4 deletion. above, please contact the Society at: FSH If you know someone who . . . As part of the experimental design for Society, Inc. 3 Westwood Road, Lexington, recruitment of subjects, 100 patients are MA 02420 USA. Phone: (781) 860-0501, would be interested in knowing needed. So far, 45 patients have been (781) 862-8422. Fax: (781) 860-0599. identified through one institution and six e-mail: [email protected]; about the FSH Society and our through another. We are asking for your [email protected]; or work or someone who would help to identify or self-identify patients [email protected]. like to support our efforts or perhaps a physician who should be aware of FSHD . . . Pregnancy & Delivery Study Requesting Participants please call the east coast office By University of Rochester Researchers at the University of Rochester are conducting a study funded by the FSH at (781) 860-0501, give us their Society about pregnancy and delivery effects on women who are diagnosed with FSHD. They are looking to recruit women with FSHD aged 18 and older. name and address and we will Participants would be asked to complete a questionnaire about their pregnancy history and give consent to review medical records pertinent to their pregnancies and deliveries. be glad to send them the The questionnaire takes approximately 30 minutes. newsletter and other If you are interested in participating please contact Deb Guntrum, NP or Christine Blood at (585) 275-6372. information about FSHD. [email protected]. 38 FSH WATCH NEWSLETTER SUMMER 2005 FSHD Prenatal Genetic Testing Now Available in US Mission Statement Prenatal FSHD genetic testing is now The prenatal FSHD test will have its own of the FSH Society, Inc. available in the United States for the first requisition form that is different from the The specific objectives and purposes of time! In the first quarter of 2005 the Uni- standard molecular pathology requisition the Corporation shall be: versity of Iowa Health Care, Department form containing the FSHD diagnostic test. 1. to create a clearinghouse for infor- of Pathology at Iowa City, Iowa USA The pricing for the prenatal FSHD test mation on FSHD, and drugs and devices began offering prenatal testing for FSHD. will be available shortly. In the interim, for the treatment of same, and to foster For further information please contact referring physicians can contact Dr. Tom communication among individuals, fami- Thomas L. Winder, Ph.D., Assistant Pro- Winder directly. lies, caregivers, charitable organizations, fessor (Clinical), University of Iowa Hospi- University of Iowa Hospitals and Clin- government agencies, industry, scientific tals and Clinics, Department of Pathology, ics, Department of Pathology has offered researchers, academic institutions, and (319) 384-7961, Fax: (319) 356-4916. diagnostic genetic testing for FSHD for interested individuals; In July 2004, Nancy Carson, Ph.D. several years. Currently, the University of 2. to accumulate and disseminate contacted the FSH Society to inform us Iowa Diagnostic Laboratories is the only information about FSHD; that the Canadian Hospital Insurance car- testing site in the U.S. that offers FSHD riers would no longer cover non-Canadian diagnostic and prenatal testing services. 3. to encourage and promote diagnostic or prenatal FSHD testing and Glenn Elbert, MT(ASCP)SH is the Labo- increased scientific and clinical research further that regrettably the hospital would ratory Manager at 6234 Roy Carver Pavil- and development on the causes, allevia- no longer be able to offer the test to U.S. ion, 200 Hawkins Dr., Iowa City, IA tion of suffering and the cure of FSHD, nationals. At that time, the only laborato- 52242-1009 USA including (with that limitation), the pro- motion of research and development for ries in the North American continent email: [email protected]. which funding may not otherwise be gen- offering prenatal testing for FSHD were in (319) 356-3533; Fax: (319) 353-6877 erally available; Canada and none of the U.S. testing sites We are grateful to the staff at Universi- offered prenatal testing. ty of Iowa Hospitals and Clinics, Depart- 4. to solicit grants and contributions Subsequently, the FSH Society contact- ment of Pathology and University of Iowa from individuals, private foundations, the ed Steven Moore, M.D., Ph.D., of the Uni- Diagnostic Laboratories for their vision, pharmaceutical industry and others to sup- versity of Iowa College of Medicine and foresight and for making it possible for port such research and development; Dr. Dev Batish of Athena Diagnostics to individuals within the U.S. with prenatal 5. to make grants and awards to quali- explain the recent development in prena- FSHD concerns to avail themselves of pre- fied applicants so that such applicants may tal testing in North America to see if natal counseling and testing within the accomplish such research and develop- either testing laboratory could expand its United States. For more information ment; FSHD testing to include prenatal FSHD please see the following University of Iowa testing. Dr. Moore said that it would be web site pages: 6. to act as a liaison among consumers timely and appropriate to review the test- and government and industry concerning FSHD information: ing to determine if it can be done. At the research and development with respect to http://www.medicine.uiowa.edu/path_ behest of the Society, Dr. Moore then fol- drugs and devices for FSHD; handbook/Appendix/Outreach/fshd.html lowed up with Dr. Carson about the tech- 7. to represent individuals and fami- nical aspects and experience with prenatal University of Iowa Diagnostic Laborato- lies with FSHD not otherwise represented FSHD tests to determine feasibility of ries (UIDL) handbook test directory by effective organizations and to work offering it at the University of Iowa. Dr. handbook page on FSHD: cooperatively and collegially with related Dev Batish stated that Athena Diagnostics http://www.medicine.uiowa.edu/path_ organizations including, but not limited to, would not add FSHD prenatal testing to handbook/rhandbook/test127.html the MDA and the National Organization its product offerings. of Rare Disorders; and After much hard work and effort, Drs. University of Iowa Diagnostic Laborato- ries Requisition form: 8. to educate the general public, rele- Moore and Winder informed the Society http://www.medicine.uiowa.edu/path_ vant government bodies, and the medical that the University of Iowa Diagnostic handbook/requisitions/mopath_req.pdf profession about the existence, diagnosis, Laboratories is now ready to accept prena- and treatment of the FSHD disorder for tal FSHD test requests. A prenatal FSHD University of Iowa Diagnostic Laborato- which funding for research and develop- test requisition form and related informa- ries Muscular Dystrophy testing: ment concerning diagnosis and treatment tion describing specimen shipping require- http://www.medicine.uiowa.edu/path_ may not be generally available. ments will soon be online at the University outreach/site/instructions/md.html of Iowa Diagnostic Laboratories web site. FSH WATCH NEWSLETTER SUMMER 2005 39 Making a Bequest to the FSH Society First Hand: Aubrie Lee Dear Mr. Perez, To help you with your estate planning, the Facioscapulohumeral Society, Inc. My husband and I are both physicians. the FSH Society researched an effective Unless otherwise specified, a bequest to Our eldest daughter, Aubrie Lee, has been way to legally request that the Society be the “The FSH Society” is interpreted as an affected since birth with FSHD (presum- made a beneficiary of your estate. Below is unrestricted donation to the Society for use ably from a spontaneous mutation), a sample form that you may use to make as directed by its Board of Directors. although the diagnosis was only made such a decision. If you desire to restrict the use of the recently. As medical personnel, we are To ensure that your bequest benefits donation for research or education, then frustrated by our inability to help Aubrie the Society, it is necessary to stipulate that to ensure that your bequest is properly intent in the terms of the will or trust. For directed and credited to the FSH Society in her day-to-day struggles. Aubrie is just example, “I give [(_____ dollars) or Research & Education Fund, rather than to entering adolescence, and the hurdles in (_____ percent) of the residue of my the Society without restriction. It is impor- front of her are unimaginable. As parents, estate)] to the FSH Society, Inc., a tant that you specify that it be paid to the we agonize every second of every day over 501(c)(3) non-profit charitable corpora- “The FSH Society, for the benefit of The what the future may hold for her. We tion based in Lexington, Massachusetts, or FSH Society Research & Education Fund.” would give anything for a cure or even its successor, to be used for general purpos- some way to stem the relentless progres- es of the organization.” While this lan- Sample Bequest Forms sion of her disease. We would give the guage may seem redundant, it is actually world just to be able to see her smile one quite important to specify that the bequest A general bequest, unrestricted as to time. is to benefit the Society directly. purpose: Aubrie is an amazing girl. She has How to make a bequest for the benefit “I give (____ dollars) or (____ percent always been the top student in her class of The FSH Society of my estate) to The FSH Society, a and, indeed, her entire school. Her art- For many donors, a bequest is the most 501(c)(3) non-profit charitable corpora- work and writing are awe-inspiring. realistic way of making a significant gift to tion based in Lexington, Massachusetts, or Despite her FSH, we believe she will make The FSH Society. You may provide assis- its successor, to be used for general purpos- an incredible mark that is uniquely her tance to the work of The FSH Society by es of the organization.” own on the world. naming the Society as a beneficiary in a We asked her to write a brief essay to new will, in a codicil to your present will, A bequest for a specific purpose: include with our Benefactor Membership under your revocable trust, or by designat- “I give (____ dollars) or (____ percent donation. We would greatly appreciate it if ing The FSH Society as the beneficiary of of my estate) to The FSH Society, a you could publish all or part of her letter your retirement plan or insurance policy. 501(c)(3) non-profit charitable corpora- in some future newsletter, and you have To ensure that your exact intentions tion based in Lexington, Massachusetts, or our permission to use it for wider distribu- are carried out, wills, codicils, and trusts its successor, for the benefit of The FSH tion, including fundraising efforts. We should be prepared by and with the advice Society to be used for (state the purpose). believe that her words may inspire others, of your attorney. The FSH Society execu- If, in the future, in the opinion of The as she has already inspired her family, tive staff is available for additional infor- FSH Society, all or part of this gift cannot friends, and teachers. mation on the various methods of be usefully applied to the above purpose We would also like to applaud you and designating a bequest to The FSH Society (or in the above manner), it may be used those others who are dedicating their lives or for guidance in planning a gift. for any purpose within the corporate pow- to improve the quality of life for everyone A bequest or beneficiary designation to ers of the Society that will most nearly with this devastating disability. We hope the FSH Society should name “The FSH accomplish my wishes and purposes.” that your efforts and fundraising may Society,” which is the common name of someday lead to a cure. We will continue to pray, not only for Aubrie, but for all those like yourself who are touched by this disease. New FSHD Bulletin Board and Chat Sincerely, The FSH Society is pleased to announce that we now have a Forum Yahoo Bulletin Emmie M. Fa & Hon S. Lee Board. Log on to http://health.groups.yahoo.com/group/fshsociety/ to post a question, talk with other members, read other people’s messages and explore links to other FSHD sites. From Aubrie: We are sure that this will be an invaluable service to our FSHD community. Imagine waking up in the morning and not being able to lift your head up from your pillow. Imagine rolling out of bed and FSH Society Welcomes LaPlante struggling with much effort to stand up. Since July 2004, Perrin LaPlante has been working in the FSH Society office as an assis- Imagine not being able to lift a toothbrush tant. Perrin is currently in her senior year at Tufts University, majoring in English, and she to your mouth. Imagine harshly endeavor- will graduate in May of this year. After graduation, Perrin hopes to enter a career of social ing to pull your sweater over your head or work or victim advocacy and, one day, possibly law. continued on page 40 40 FSH WATCH NEWSLETTER SUMMER 2005

Aubrie, cont. from page 39 First Hand: Justin Cohen tug your pants to your hips. This is merely Hello everyone, I’ve been really busy because of the finals, but a morning of getting ready through my now school’s over, so I can finally do this. My name is Justin eyes. Try to picture an entire day with Cohen (13 years old) and I was asked to write this article based FSHD. A week. A month. A year. on my experiences for my FSH is a MD that affects my face, Bar Mitzvah. arms, and general strength. However, I’m This project started able to compensate for most of the restric- out as a service project tions. I am unable to move my lips or the customary for bar- and area around it, so I use my tongue to move bat-mitzvah children at my temple. With a little around food inside my mouth. In addition, help, I got the idea of my eyelids can’t close tightly to keep out making cards. After posting a note on the board water and shampoo while I take a shower, (FSH Society website, www.fshsociety.org), I got so I merely lean my head back to prevent several people who volunteered to make some pic- them from flowing into my eyes. As for my tures for the cards and the whole project started. arms, I can’t lift them above my shoulder We started selling them to friends and family members who told their friends, and we had height. Therefore, to put on a sweater, I a chain that went on for a few months. This was the start of a great project. have to prop my elbows on a platform so I had a little bit of difficulty on the project. One of those is deciding how I was going to that they’re level to my shoulders and do this project. With a little help, I contacted a few adolescents with FSHD with the help then tug on the sweatshirt to pull it over of Carol Perez and the project began. It was a great project my head. That method is the same for which made me think how easy it was to find a way to brushing my teeth, but my elbows don’t donate money for a great cause to help all of us affected have to be quite so high. Furthermore, with FSHD. I would recommend others to do the same FSH limits my overall physical strength. I thing that I did, it is relatively simple to do, and in the end can’t run properly and I walk with a slight produces a good amount of money. limp. Anyhow, I manage to persevere The reason that I picked this project was that as a where I’m headed. Some things that others child with FSHD, I am the only person that I know that consider light, I consider heavy. These has been affected with FSHD. I was able to communicate objects are difficult for me to lift. Conse- with others with the disease, and this made me feel com- quently, I can only carry a certain amount fortable that I wasn’t the only person with the disease. Attached are pictures of the cards which have been of weight and only for a specific amount of sold out for months. We raised over seven hundred dollars. time before my arms tire. Additionally, I Maybe enough to find a cure. fatigue rather easily when I go anywhere or Justin Cohen complete any arduous task. I often stop to Note: Justin’s fellow artists were Haley Cohen, Yann Dardonville, Leticia Estevez and rest to replenish my energy. Nicolas Pogany. Nevertheless, I have many talents. Someone might take a look at me and think, That girl has a handicap. On the other hand, I regard FSH as a gift. It exer- cises my mind to conjure up creative ways Dardonville Creates Art End of Tax Season Bar to compensate, strategies to study the situ- Cards to Raise Funds for Crawl Raises Funds ation entirely and find out more than one FSHD Chris Stenmon has been part of the way to see it. It enables me to counteract FSH Society’s New England group since he the circumstances so that I may even be Inspired by participating in Justin was sixteen. A staunch supporter of the able to accomplish a feat that a powerful, Cohen’s project, Yann Dardonville decided he would like to make postcards and sell FSH Society, Chris, a CPA, runs the Annu- physically strong person wouldn’t be able them to benefit the FSH Society. Yann was al End of Tax Season Bar Crawl for the to. This ability gives me a great strength in so successful in his project for us that he art, poetry, and creative skill. I love to FSH Society. Companies, friends, local contributed $450. draw and design all-new creatures, animals pubs and bars contribute to this fun event Yann is the son of Catherine L’heureux for the Certified Public Accountants and and vegetation that don’t exist on earth. and Christian Dardonville, recent émigrés their staff raising almost $5,700 in its sixth My imagination has grown to replace the from France, who have settled in Washing- physical strengths that I am deficient in. ton state. Catherine organized the FSHD year. If you are in Quincy, Massachusetts What I lack in muscle, I counterbalance in group in France and serves as the FSH at the end of the tax year, you can join mind and imagination. Society’s liaison to the French Amis. Chris and his friends in their annual Aubrie Lee, age 11, Hillsborough, CA Yann Dardonville, age 6 fundraiser. FSH WATCH NEWSLETTER SUMMER 2005 41 The Third Choice Fiction by Michael H. Brooke, MD, FAAN Indeed, you could tell nothing from his any friends. He would never meet anyone It was afternoon. The old leather chair expression because he did not have one. or get married or get a job. He might as was backed up against the wall, scarred His face was immobile. There was no flick- well die. from years of comfortable abuse and too er of movement from the forehead or Thirty years ago was a long time, but many experiences with the movers. The cheeks. The skin was pale and the whole the old man remembered the conversation old man tidied up the lunch dishes and face was as if carved from alabaster. The well. “Grant, you have two choices. One, pulled a book from the shelves before lips were held immobile and slightly parted you can accept who you are and what you going over to sit in the afternoon sun that in a continual pout. They were flat, drawn have, tragic though it is, and try to get on lanced through the window. Motes by a child on a cartoon face. The lower with living in the real world, because that sparkled. There was nothing on the radio eyelids were turned slightly outwards so is really all there is. Or, two, you can hide and he hadn’t yet capitulated to his chil- that the pink lining of the conjunctiva was away in a closet for the rest of your life so dren’s insistence that he buy a television visible. Only the eyes moved as, every so that you don’t have to face anybody.” set. A book was as good a way as any of often, Grant gave a convulsive swallow in When he looked back, it made him realize starting his afternoon siesta. He looked an effort to blink and the eyes rolled up what a failure he had been to so many of forward to the comfortable warm drowsi- under the upper lids. It was the most strik- his patients. Many years later, the old man ness that was almost predictable after the ing case of FSHD that the old man had had been staying with his son in Denver first few pages. It was a favorite of his: “A ever seen. for the weekend. The two of them always la Recherche du Temps Perdu.” He only Grant and his family were regular visi- had a good time together. “Dad, have you understood about one sentence out of tors to the clinic and, every time, the lad heard about Robin Hood?” his son had three, but the ones that he did understand had some story or other. At first they had enquired. The old man had growled a often turned out to be zingers, although been of the “Knock knock!” variety, but as response appropriate for someone born what Marcel was on about with all this time passed they became more refined. It only 40 miles from Sherwood Forest. The “involuntary memory” stuff was a bit had been when Grant was 13 that he had result, though, was that on Saturday night vague. He settled himself into the chair, come into the clinic and, as soon as the he had found himself in a place that he which greeted him as befitting an old old man had entered the examination would never have chosen on his own. It friend. room, Grant had launched into “Hey, Doc. was a club just off Larimer Square, which A little while later, he was staring at Did you hear about the two men in a bar. billed “Robin Hood and his Merry Men.” the page or, more accurately, through the One turns to the other and says ‘Are you The old man had sat doubtfully through page when the chimes from the computer Irish?’—” The 13-year-old boy told the the first couple of acts, trying to adopt an in the small alcove brought him to wake- rest of the story with considerable skill and expression suited to the occasion. Since fulness. E-mail had arrived. Since he had the old man had been so amused that he the occasion was a series of songs of unre- filters on, which cut out most of the spam, laughed out loud for several seconds. He quited love belted out at a volume that he could be fairly sure that the message then looked at Grant’s impassive face and made his teeth ache, this had not been was from somebody he knew. Putting his noticed the boy’s eyes. They were moist easy. The Master of Ceremonies had then book down, he pushed himself out of the and small drops were running down one announced the main attraction and onto chair and walked stiffly over to the side of his nose. It took the old man a few the stage tumbled a motley collection of machine. The e-mail was from his son, seconds to realize that Grant was crying, jongleurs and acrobats. They were tolera- who worked in information technology in but whether they were tears of joy or of bly good and it reminded the old man of the southwestern part of the States. His sadness was a mystery. The old man had his days in the circus. There was a crash of was a demanding job, but not so consum- passed the box of tissues and asked gently cymbals. Well, actually, it had been one ing that he had no time for daily bulletins “Is anything the matter?” “I’m a freak, rather small, tinny cymbal and the spot- to his father. The old man looked forward Doc! How can you ask if anything is the light swung over to a striking figure that to them and had become used to the jokes matter?” It was a long conversation and stepped onto the small stage. He was tall that often accompanied them. Today was had made the old man realize how foolish and angular and dressed completely in no exception. “Hi, Dad. There were two he had sounded. The boy was friendless. dark green. “Robin Hood!” puffed the guys in a bar. One turns to the other and He lived a lonely life isolated from the rest master of ceremonies. Robin began to says ‘Are you Irish?’—” The old man of the world by a face that wouldn’t work. deliver one-liners with staccato precision. grinned. It was an oldie, which he had If anyone came to talk to him, there was The old man, who had been prepared to heard before. He tapped at the keyboard no way he could show a normal emotional tolerate whatever fate and the talent “Hi, Son. Get some new material!—And response. He could not even frown. If they agents could throw up, had found to his get back to work!” He pushed the ‘Send’ were pleasant enough to try to get to know surprise that the fellow was really good. He button and sat back. The joke was at least him better, his face remained as cold and had ended up bellowing and banging the 30 years old. He had heard it first from a impassive as a headstone. In fact, he said, table along with everyone else for the 45 patient. When Grant came to the clinic as that is what he had; not a face but a head- minute piece. Even the old “There were an 8-year-old boy, the old man had been stone. If he tried to laugh at someone’s two guys in the bar. One turns to the other struck by how cheerful the child was, not pleasantry, a mirthless braying was all that and says, ‘Are you Irish?’—” was told that you could tell from his expression. he could produce. He would never have continued on page 42 42 FSH WATCH NEWSLETTER SUMMER 2005

The Third Choice, continued from page 41 superbly. When the son had turned to look door and entered, shutting it behind him. and face were completely covered with a at his father at the end of the set, he was He had been in vaudeville dressing rooms hood of the same color and fabric. The old disappointed to see him staring at his beer before and this was pretty standard. There man saw a sudden gleam through the eye as if stricken. “You OK, Dad?” “I’ll be fine was a mirror on the far wall framed by a slits as the comic turned to look at him. in a moment. You just have to excuse me handful of naked light bulbs. A crack was Grant got up awkwardly from the chair, for a minute.” working its way across the glass. Some pulling off his hood as he did so. His face The old man had made his way out of photographs of anonymous performers was still the same, unlined and expression- the club and down the back alley behind it hung on one of the walls. A couple of less. His eyes were a little redder than until he came to a rough wooden door chairs, one with a spring making its way before. with bare wood showing through paint through the upholstery, were placed at odd The old man remembered, as if yester- that was decades old. Stenciled across it angles. The only unusual thing was that day, the stinging in his own eyes and the were the words “Stage Door. No Entry.” there was no smell of makeup and the blurring of his vision as he had gone over He went in. In front of him stood a burly dresser below the mirror was empty of any to Grant to shake his hand. “Hi, Doc,” giant of a man, wearing torn jeans and a of the usual cosmetic jars and grease paint Grant had said. “This was the third T-shirt that advocated an unproductive sticks. choice.” form of procreation. “Where you think Robin Hood was sprawled on one of Address correspondence to Dr. you’re going?” “I have to see Robin Hood.” the chairs. On a small table by his side was Michael H. Brooke, University of Alberta, The behemoth looked dubious. “It’s all a half full glass of wine. He was dressed 87th and 112th Sts., Edmonton, AB, T6G right, I’m a doctor.” An aurora of compre- exactly as he had been on stage. He wore 2S2, Canada; e-mail: [email protected] hension spread slowly across the large face. a one-piece dark green body suit. There Copyright © 2004 by AAN Enterpris- “Oh, sure Doc. Second door on the left.” were no adornments of any kind except for es, Inc. Reprinted with permission 12 Jan- The old man had knocked quietly on the a wide black belt around his hips. His head uary 2005.

Scooting Across the Sea by Carol A. Perez, May 16, 2004 When I spoke to him a couple of days ago, Executive Director, Dear Carol: he was, for the first time in several FSH Society From the moment you entered our months, cheerful and positive and alive One icy March lives through the phone call, I knew that again. day, the phone you are a very special lady. Your caring Thank you for giving us hope and love rang in the FSH attitude, your understanding and willing- when we needed it the most. You became office. Natasa ness to take part of your time to care for a friend to our family and you will always Mihajlovic, a others was really impressing. It meant a lot stay in our prayers. Your tireless energy graduate student to me that you were able to understand that you pour into your work is priceless. I in Michigan asked the problems and obstacles that a lot of am sure that a lot of people would agree if we could get a people cannot relate to. with me that your love for people and power wheelchair for her father with MD Furthermore, you showed us that there sense of mission has made a huge differ- in Bosnia and Herzegovina.The health are much more to finding a scooter than ence. services in his country would only provide just to look for any kind. You taught us Natasa manual chairs and thus her mother had to how to look for what we exactly needed push him everywhere. We gave Natasa a and pointed to the areas that we were not list of questions for her mother and father thinking about. Thank you for your time July 8, 2004 to answer. With that information, we and infectious energy and zeal for life that Just to give you an update, everything found that her father could use a scooter gave hope and courage and extra energy went well with the transportation and my in their house and outside. When Natasa boost that we needed. dad is really excited and he is back to life. called back, Dan and Carol suggested that Even more, thank you for being so Now, when we go somewhere, he “walks” she contact the Amigo Company since it is resourceful. Thank you for asking me to faster than we. We are so happy. located in Michigan. As it turned out, contact the My Amigo store. They showed Thanks again for your love and sup- Amigo had a donated scooter available for me so much compassion and willingness to port. Natasa’s father. Natasa and her husband help and they were actually able to find a Natasa picked up the scooter directly from Amigo donator for my father’s Amigo. and packed it for their return trip. Now My father is slowly recovering and he Natasa’s father was able to be independent is actually very excited about receiving the and return to activities including working scooter. He was depressed over his situa- P.S. Natasa’s father now plans to set up for his church. tion and tired of sitting at home. However, a support group for the disabled in his At right is the letter received in May since he heard about the scooter, every community. in Bosnia and Herzegovina. and the follow-up letter in July. time I talk to him he asks about its arrival. FSH WATCH NEWSLETTER SUMMER 2005 43 Visit us @ Acknowledgements www.fshsociety.org Special Events Lund, WI; Tim Nelson, WA; Janet Peter- by Daniel Paul Perez, President & CEO, Bear Creek Elementary School, son, WA; Steve Power, PA; Michael FSH Society Baltimore, Maryland 2003 & 2004 Quam, WA; Mark Stern, OR, Delton Visit us and bookmark the FSH Society Read-A-Thon Fundraiser: The Bear Summers, GA; at its online Internet location www.fshsoci- Creek Elementary School held the 2003 & First Annual Memorial Weekend ety.org. The web site is still going strong 2004 Read-A-Thon Fundraiser to support 2004 Yard Sale: Grace Corradino, NY. and we are seeing a tremendous increase the FSH Society & educate their commu- (See article page 43.) in both domestic and international traffic. nity about FSHD. 2004 was the eighth Yann Dardonville’s Card Sale: We are getting the word out about FSHD! annual Read-A-Thon honoring Arlene (See article page 40.) The home page at www.fshsociety.org Endres, mother of Jessica Ryley, & teacher 2004 Gala Benefit Evening of contains a rich resource of material for at the Bear Creek School. (See article Chamber Music & Song to Fund Con- those interested in FSHD. For those not page 43.) tinuing Research by the FSH Society: familiar with the site, the FSH Society Howard Chabner’s Friends & (See article pages 7-10.) Aegean Restau- home page contains information on the Family for the FSH Society: Buffalo rant, Noa Ain, @SQC Restaurant, Diane following: the FSH Society; FSHD; the Rides Inc. (Elliott & Sharon Slusky), TX; Bondareff, Caprice Café, Carnegie Hall, FSH Society online bulletin board and chat Barbara Chabner & Marshal Datkowitz, Susan Egert, William Egert, Feline Day room; and previous FSH Society publica- NJ; Michael & Marla Craven, IL; Kathy Spa, Fidelity Investments Charitable Gift tions and information. The chat room, Dees & Dwight Dickerson, CA; Howard Fund, Susan Glasser, Great Aunt Fannie’s hosted by Paul Closson, meets every Sun- & Susu Fine, CA; Morton Frank, CA; Attic, Henry’s Restaurant, Marvin & Sons, day 2 p.m. and 9 p.m. eastern time zone. Steven & Keiko Franklin, CA; Stewart & The New York Philharmonic, Geraldi Nor- Professional web designers and web Rochelle Grill, IL; Stewart & Rochelle ton Memorial Corporation, Martin and architects who would like to volunteer Grill’s Philanthropy Fund, IL; Michael & Suzi Oppenheimer Philanthropic Fund, their time and services are encouraged to Lisa Heyison, MA; Gary & Courtney Jack- Ben Schonzeit, Judith Seslowe, and The contact us. We fully appreciate the contri- son, NC; Sherwin & Betty Korey, IL; Westerleigh Press. Our thanks to the New butions and donations made to date to the Jerome Kraut, IL; Doug Morton & Paula York Philharmonic and the New York Fes- Society to support this important and time- Jackson, CA; Sandy & Anita Pensler, NJ; tival of Song for donating their involve- ly resource. Please consider making a John & Lynn Peterson, CA; Michael & ment with the Benefit and to Phyllis J. donation to the FSH Society Internet fund. Lisa Radin, IL; Seymour & Barbara Regal, Mills who generously underwrote the We look forward to seeing you on-line! IL; Judith & Allan Rosenblum, IL; Jacque- major costs of Symphony Space and the line Savoy, CA; Drs. Aaron & Suzi Siegel, reception for this Benefit evening. IL; Seymour & Lois Siegel, IL; Michael & Bill & Judy Herzberg’s Friends & Read-a-thon at the Bear Stephanie Smerling, IL; Denise & Steven Family for the Research & Education Creek Elementary School Soberanis, CA; Lee & Debbie Spector, IL; Fund 2004: Richard & Marci Gerhard & Ethel Spiegler, PA; Dr. & Mrs. Abramowitz, NJ; Alan Abramson, NY; Since 1997, Arlene Endres has held a Herbert Stein, CA; Barry & Joan Swirsky, Michael Agliardo, CA; Norman & Sandra read-a-thon at the Bear Creek Elementary NJ; Kathryn Thyret, CA; Rosalyn & Judd Arky, FL; Dr. & Mrs. Ronald Arky, MA; School in Baltimore, Maryland. The chil- Wenner, CA Stanley Arky, FL; Kerry & Mia Barnett, dren read books and get contributions to Justin Cohen’s Bar Mitzvah Pro- OR; Tracey Barnett & Simon Mrvucic, benefit the FSH Society. Arlene has been ject: (See article page 40.) OR; John & Rene Beglan, NJ; Joseph Ben- active in the FSH Society and the Mid- The Colella Family: Elaine Attias, david, NJ; Susan Bloom & Mac Kieffer, Atlantic group in Maryland. Working with CA; Kathryn Barnard, WA; Nancy Bres- OR; Andrea Borsuk, OR; Philip & Bar- the Society, Arlene fights for a cure for her lich, WA; Marilyn Burke, WA; California bara Borsuk, CA; Ernesto & Connie daughter and all the FSHD patients. Community Foundation, CA; Wylie Brauer, WI; Stanley & Judith Broadwin, Chenn, UT; Lynn Colella, WA; Steven NY; David Brotman, NJ; T. J. Browning, Colella, TX; Edythe DeVries, FL; Richard OR; Christer & Laurel Cederberg, MN; First Annual Memorial & Sandra Eacker, WA; Robert Elsas, WI; Mark & Anabella Charwat, NY; G. Alan Weekend Garage Sale Elizabeth Evans, WA; Eloise Fritz, AZ; Pat & Leslie Comnes, OR; Rose Dubrow, NJ; Ariel & Mariela Dybner, NJ; Dr. Ruben & Organized by Grace Corradino, the Graham, WA; Ralph Heritage, WA; Sallie Ana Dybner, NY; Albert Fano, NY; First Annual Garage Sale was successful Herling, WA; Virginia Lloyd, WA; Mariel continued on page 44 and contributed to the FSH Society Research Fund. Grace, Brian Kerr, and Kyle and Joy Pablo held this sale over the Adapted Van For Sale Memorial Day weekend in NY with plans 2004 Chrysler Grand Caravan with 12,000 miles – excellent condition. to do this annually. Kyle graduated from Fully adapted by Entervan with ramp, hand controls, wheelchair tie downs. high school in June and is attending the Specifically adapted for driver in wheelchair with FSHD. University of California, Berkeley. For further details, please contact Dean Johnsen at (301) 262-0701 in Maryland. 44 FSH WATCH NEWSLETTER SUMMER 2005

Acknowledgements, continued from page 43

Michael & Marie Ferragamo, NY; Rebecca Sidney Triefler, NY; Stacey Vallas & Reiner New United Motor Manufacturing, Fleischman, OR; John Freedman & Lisa Warschauer, OR; Vancouver Neurologists, CA Cohen, MA; Maximo Giesen, Spain; Bar- WA; Courtney & Anthony Vengarick, Pepsico Matching Gifts, NY bara Gilson, OR; Louis Goldstein, NJ; OR; Ernest Weiss, FL; Merrill Weyer- Price Waterhouse Marcia Goldstein & Fred Levick, NC; haeuser, OR; Milton & Joanne Yatvin, Research Systems, Inc., CO Harriet & Alan Gordon, NJ; Lynda Gor- OR; Paul Zemsky, NY Schering Plough don, MA; Stephen & Alice Goshorn, WA; Christopher Stenmon’s Sixth Elva Granat, CA; Enrique & Ruth Gut- Annual End of the 2004 Tax Season Bar man, NY; Howard Haberman & Martha Crawl: (See article page 40.) Alba Bar & Foundations Lybarger, CA; Roberta Harris, IL; F. Peter Grill; Lara Apovian; Beachcomber; Bikram Academisch Zeikenhuis Leiden, Herzberg, NY; Mark Herzberg & Patricia Yoga & Massage Allston; Boston Volvo The Netherlands Sheridan, NJ; Mitchell & Marci Heskel, Village; Sheri Buckingham; Megan Carey; Association Francaise pour les NJ; Steven & Linda Hill, NY; Elisa & Bill Lauren Carnes; Jeffrey Caruso; Stephen Myopathies, France Hirschberg, NY; Michael Hirschberg, NY; Cavicchi; Lorraine Chapman; Shane Marjorie & Gerald Bronfman Foun- Ruth & Alan Hirschberg, NY; Judy & Christiansen, ME; Club 58; Steven J. dation (See article page 17.) Everett Hirsh, CO; Edna & Harold Hirsh- Cohen; Crosshaven Partners; Erin Cum- Delta Railroad Construction, OH man, NJ; Beno & Fredalee Hubler, NJ; mings; Chad Dagraca; Kimberly Eddy; (See article page 17.) Karen & Eric Hubler, CO; Beth Hutchins Andrew Fink; Jason Forish; Jennifer Gar- Fidelity Charitable Gift Fund & Pete Skeggs, OR; Paul & Jane Jacobsen, neau; Annette Godin; Rita Guerin; David Geraldi Norton Memorial Founda- WA; Seymour & Lola Kamp, NJ; Margaret R Huck; Kate Hurley, NY; M. Douglass tion, IL Katz, NY; Maria Katz, NY; Karen Keusch, Hurley; Gail Kenerson; Ulrike Kjellberg; Greater Kansas City Community NJ; Barbara Kim, OR; Irvin Kirschbaum & Le Disco, Inc.; Francis P. Leone; Scott Foundation, MO Shawn Greenleaf, CA; Iris Kislin, NJ; Lewis; Jennifer Lilley; Joanne P. Maguire; Muller Family Foundation, CA Samuel & Shirley Knopf, NJ; Katherine Linda Maregni; Joseph Marnikovic; Nancy New York Community Trust Foun- Koelle, CA; Cheryl Kollin & Bill Franz, Marrese; Anne McDonnell; O’Connor & dation, NY (See article page 18.) MD; Jonathan Koomey, CA; Peter Korn & Drew, P.C.; Kevin Pellerin; Lisa Pellerin; The San Diego Foundation, Kurtz- Betty Smith, OR; Sandford & Dorothy Michael A. Powers; Stephen Riden; man Family Fund, CA Landa, FL; Michael Lanza, NY; Rubin & Annette Roberts; Michelle Robinson; Tides Foundation, CA (See article Sally Laskoff, ME; Ingrid & Daniel Laub, Michael A. Rozman, NY; Sailfish Enter- page 17.) NY; Al LePage, OR; Kenneth Lerner & prises; Jenn Salamone; Sarsfield, Inc.; United Way Special Distribution Katherine McDowell, OR; Anna Marantz, Christopher Spillane, NH; Geraldine Account CA; Calvin & Myra Marantz, CA; Lori Spillane; Russell C. Stamm; Julie Marantz, MD; Myra & Marvin Marantz, Steinkrauss; Christopher Stenmon; Jo Ann The following individuals requested to be NJ; Philip & Susan Marantz, NJ; Scott Thorpe; Frances A. Uftring; Bridget acknowledged in the FSH WATCH as of Marantz & Susan Laskoff, CA; R.A. Valeri; Ellen Weber; Dianne Wolpert; March 31, 2005: Markel Family, PA; Enrique & Amanda Sharon Zidek. (All donors located in MA New & Renewing Members Martinez, MD; Cathy May Miller, CA; except where noted). Steven Awtry, GA; Joann Ayers, CA; Enrique More, NJ; Patrick Nance, CA; Randy Berenfield, FL; Ann Biggs-Williams, David & Elsie Napell, NY; Laura Natkins Matching & Charitable Programs AL; Jeri Blom, MN; Jerzy Boroch, France; & Peter Gradjansky, CA; Ina Nelson & Stephen Bradford, CA; David & Beverly Alliant Energy, WI Cheryl Minkoff, NJ; Dr. Leon & Barbara Brittain, FL; Barbara Brown, GA; Miriam Allianz Insurance Charity Program, Nesis, NY; Marty Paddock, CA; Ellen & Brown, PA; Lori Calandro, MI; Deborah Alex Passannante, NY; Dr. & Mrs. Hector MN Calhoun, MN; Jeanette Campbell, CA; Retik, NY; Marion Rinehart, CA; Joan Dr. Amgen Foundation, CA Theresa & Chris Carrino, NY; Peter & Rockhill, FL; Andrew Rosenbach, CA; Anheuser Busch, MO Nancy Carrothers, TX; Piyush Chawla, Ingrid Rosenthal, CA; Herman & Martha Chase Manhattan Foundation India; Rita Chestnut, KS; Paul & Rotter, NY; Saitowitz Family Trust, CA; Combined Federal Campaign Annabelle Closson, FL; Elizabeth Coar, Leon & Eileen Saitowitz, CA; Mark IBM, NY NJ; Gary Cohen, M.D., NY; Ken Colosi, Saitowitz, OR; Norman Schlesinger, NY; Johnson & Johnson Matching Gifts Program, NJ NY; Mr. & Mrs. Dennis Darst, MI; Larry Mitchell Schoenbrun, CA; Stephen Schot- Dressler, CO; Doris Embry, TX; Emelina Merck Employee Giving Campaign, land, CA; Edith Schwartz, NJ; Drs. Fa, CA; Barbara Finlay, Canada; William Ernesto & Mirta Seldman, NY; Gerald & NJ & Cynthia Fish, TX; Charles Fitts, MS; Pearl Siegel, FL; Sheila Siegel, NJ; Steven Merrill Lynch Matching Joann Forance, FL; Rick & Leslie Frye, Slovic & Rhonda Schwartz, OR; Ralph MIT Annual Community, MA WA; Deborah Gemmi, FL; Frank Gianino, Staver & Amy O’Neill, OR; Bryan & Ilene Morgan Stanley Appeal, NJ MA; Manuel Gomez, WA; Gordon Gree- Steinberg, MD; Morty & Zeta Sudler, FL; MRP Lawrence Marketing Inc., NY National Football League, NY continued on page 45 FSH WATCH NEWSLETTER SUMMER 2005 45

Acknowledgements, continued from page 44 ny, IL; Laura Grimes-Hartley, MD; Seglin, IL; Seymour Siegel, IL Severn; Beverly K. Kneessi, FL; Maureen William Hall, LA; Mary Haraway, AL; Beverly Crompton: Marilyn A. Lawson; Rev. & Mrs. Loiselle; Donald Anne Harland, Canada; Olga Harris, NV; Limpede, TX; Harry Shorey, Jr., MT; & Judith Lokerson; Robert & Valerie William & Judy Herzberg, OR; Arlene & Wade-Trim, MI Lumsden; Richard & Dorothy McKinney, Marvin Hoffman, MD; Isabel Jeffares, GA; Stanley Deiches: Stuart Cohen, NY VA; Joan & Kerry McPhillips, CA; Nor- Ray Jordan, Australia; Hilary Kawelo, HI; Don Draper: Elizabeth Bove, PA man & Shirley Martin, GA; New York Valery Kazakov, Russia; John & Donna Solomon Eisenberg: Rose Kanter, Community Trust Anonymous Donor, NY; Kirtz, TX; Florence Koplow, MA; Melissa NY Shirley Novotny; Doris Olds-Eck; Carol & & Greg Kuersteiner, NY; Russell Lai, CA; Joseph Elkins: W.D. & Judy Ross, Charles Perez, MA; Daniel P. Perez, MA; Stuart Lai, NY; Catherine Lheureux, WA; WA Margaret & Michael Powers, AZ; Kathryn Lawrence & Agnes Liptak, VA; David Julie Gitlitz: Eli Schindelheim, NY Presley; Dorothy & Ferdinand Prokes; Lokerson, MD; Donald & Judith Loker- Rose Goldstein: Rose Kanter, NY Amirali Pyarali; Kathryn & Les Riordan; son, MD; CJ Lucas, England; Bernadette Joseph Grech: Frank Agius; Attard Karen Ritter; Jody Roesler & Mickey McNulty, CA; Daniel Mennetret, France; Upholstery; Catherine Beltrami; Karen Courtney; Amy Ross; Sandy Spring Bank; Louise Merkle, FL; William & Ginny Bettucchi; Edwin & Maria Bonavia; Cali- Edward Schechter, PA; Ed & Beth Michael, MA; Patrick Morris, FL; Peggy fornia Parking Company; Doris & Reno Schmahl; Kathy Segar; Ronald & Lisa Ses- Morris, FL; Harry Mulholland, North Ire- Camilleri; Raymond & Susan Celentano; soms; Nancy J. Spinney; Hilda & Edward land; Jai Narayan, NJ; Roy Neilson, CA; Joseph Chetcuti; Paul & Annabelle Clos- Steiner; John & Suzanne Stekly, MA; Dr. Leon & Barbara Nesis, NY; Stuart son, FL; Angela Grech; John Grech; Peter Sunny Acquisition Corporation; Kusum Novick, FL; Scott Oberlin, OH; Martha Grech; Kristine Knight-Cushing; Martin Swami; Janine & Alain Thys; William & ONeal, FL; Gerald Organ, England; Vir- Meier; Oakley Veterinary Medical Center; Janet Travers; Peter & Suzanne Verkouw; ginia Padberg, MO; Carol & Charles Perez, Maureen O’Sullivan; Daniel P. Perez, MA; William Wesley Jr. & Alice Latonik, FL; MA; John & Lynn Peterson, CA; Peter Donald Perry (All donations are from Cali- Susan Wilson, MA; XTZ (All donations Pogozelski, CT; Margaret & Michael Pow- fornia except where noted.) are from Maryland except where noted) ers, AZ; Armando Quiroz, NY; Stephanie Thelma Green: Ron Baxter, MI To the memory of Karen Johnsen in Biggs Rentfro, GA; W.E. Richards, TX; Lady W. Hall & Lady Beth Hall: the memory of Jillian Abrams: Doris Olds- Judith Rosenblum, IL; Robin Roush, MN; William Hall, LA Eck, MD Mike Rowlett, TX; Kelly Sanderfoot, WI; James Healy: Maureen Healy, NY Janet Kerr: Gloria Abramowitz, NY; Evelyn Schuster, MA; Mr. & Mrs. Sherr, Dr. John A. Holmes: Forrest Erick- Fair Harbor Fire Department, NY; Keith & NJ; Allan Silverstein, NY; Brad Simpson, son, KS; Elizabeth Holmes, KS Carolann Fulk, VA; Barbara Kastner, NY; MO; Stephanie Staley, CO; Monti Staton, Karen Johnsen: All Saints Lutheran Jonathan & Bobbie Leigh, NY; John & Al GA; Dr. Herbert Stein, CA; Christopher Church; Janet Allen & Ralph Fierro; Ruvolo, NY Stenmon, MA; Gwen Stribling, MN; Michael A. Aquilino; Connie Arnett- Bernard Kislin: Iris Kislin, NJ Verna Taylor, NC; Maximilian Teleki, DC; Ward; Katie & Bob Berry; Marcus & Kelly Sam Levinson: Bryna Blaine, MD Robert Trumble, MI; Jennifer Valentine, Berry; Ann Biggs-Williams & the Gulf Mrs. Caryl Lewis: W. D. & Judy NY; Silvio Vatovec, NY; Michael Wagner, FSHD Support Group, AL; Charlotte Ann Ross, WA MN; Doris Walter, MD; Matthew Wick- Brown; Christina & James Burcham; Deb- Victoria Liptak: Genevieve Elie, lund, TX; Cyrina Wolf, OH; Bob & Mary orah Burcham; James & Sharon Burcham; MA; Mildred Irzyk, MA; Phyllis Kielkoski, Wood, AR; Christiane Wyckoff, GA; Patricia Burcham; Sharon Burcham MA; George Liptak, MA; Christine Mar- Helen & Marc Younger, NY; W. Saleha through the Advanced Learning Center, tin, MA; Elizabeth Strycharz, MA Yunus, Malaysia CO; Jeanne Chicca; Check & Peggy Grandmother Bertha Lob: Miriam Cicollini; Gary & Carol Clary; Paul & Brown, PA Annabelle Closson, FL; Collington Lodge Walter Mansfield: Ann Biggs- Professional Memberships No. 230; Albin & Dorothy Collins; Judy & Williams, AL Judith Birnbaum, CT Tom Cusick; Thomas & Dana Delaney; Her father on his Birthday: Linda Sara Winokur, CA Hillard Donner; Paul Eck; Robert Eck; Mason, KS Robert Eck & Doris Olds-Eck; Eugene & Virginia McCormick: Lova Sue Memorial Mary Ann Elliott; Raymond & Pamela Robbins, NJ Mildred Brelman: Miriam Brown, Enrico; Barbara Finlay, Canada; Nancy William “Billy” T. Michael: Fred & PA Garrett; James & Carol Golden; Ali Mary Adams; Allan, Pauline, & Theresa Walter Chwick: Bryna Blaine, MD; Goode, FL; Claire & Grace Hayward; Ashley; Diane Baker; Gladys & Lynne Terry & Sharon Kilpatrick, MD; Harris Kathi Heron; HVAC Systems University; Bleakney; Mary F Campbell; Ritajane Levinson, NY Virginia M. Johnson; Tom Kammerer; Clancy; Norma Connolly; John Crisafulli; Sarafina Connelly: Diane Morse, Louise & B. J. Keister; Joyce Gillen Ken- Judy & Arthur DeArruda; Barbara A. NY ney; Joanne Kerr; Kiwanis Foundation of Evans; Sheila & James Goldrick; John & William Crane: Dr. & Mrs. Melvin Crofton Maryland; Kiwanis Club of the continued on page 46 46 FSH WATCH NEWSLETTER SUMMER 2005

Acknowledgements, continued from page 45

Virginia Grant, FL; Daniel & Madeline TX; Kimberly Karl, TX Bea & Harry Herzberg: Myra & Gregory; Pat Hoitt; Harry Hoyt; Theodore Janet & Jason Caldwell: Paul & Marvin Marantz, NJ LaBelle; David Lee; Fred & Susan Meyers; Annabelle Closson, FL Bill Herzberg on Father’s Day: James Meyers, CA; Mr. & Mrs. Ronald Glen Chestnut: Verla McDermed, Myra & Marvin Marantz, NJ Michael; William & Ginny Michael; Mur- KS Bill & Judy Herzberg’s Anniversary: phy & Beane; Jeannine Olinger, IA; John Haley Cohen: Cathy Robbins, NJ; Myra & Marvin Marantz, NJ & Janet O’Reilly; William Penney; Carol Lova Sue Robbins, NJ Harry Herzberg: Cheryl Kollin & & Charles Perez; Daniel P. Perez, MA; Justin Cohen: Stuart Cohen, NY; Bill Franz, MD Ronald & Melody Perry; Larry Pratt & Judith Cotler, NY Judy Herzberg’s Birthday: Myra & Rosalind Forber; PSA Brockton Nursing Justin Cohen’s Bar Mitzvah: Ted Marvin Marantz, NJ Imprest; Dr. Patrick & Riddle; C. Earl Rus- Sicker & Ron Kelter, MA; Rose Kanter, Karen Johnsen: Kiwanis Club of sell; Joanna Savage; Ana Severino; John & NY; Donald Stern, FL; Gary Cohen, M.D., the Severn, MD, Doris Olds-Eck, MD Erin Shea; John & Suzanne Stekly; Wendy NY, The Katz Family: Linda Ketelaar, D. Stout, NY; Charlotte Surgenor; Carol Justin Cohen’s Bar Mitzvah Project: SC Anne, Rosemary & Jane Waldron; Paul & Gary Cohen, NY Aubrie Lee: Laurie & Bill Daniels, Theresa Waldron; Henry Wiggin; Marion Justin Cohen’s Birthday: Rose CA Willard; Anthony & Joan Zacconi (All Kanter, NY Dick Lefebvre's Birthday: Marie donations are from Massachusetts except Yann Dardonville’s Card Sale: son Bortone, MA where noted otherwise.) of Catherine Lheureux-Rouslin, WA Anna Marantz’s 90th Birthday: Bill Lorayn Miller: Sharon Anderson, Her brother Joe: Mary Ann Davies, & Judy Herzberg, OR; Seymour Kamp, NJ; MN CA Rubin Laskoff, ME; Myra & Marvin James Reichmann: Dona Wagner, Sarah Love Davis: Grandfather, Mr. Marantz, NJ MN Charles M. Fitts Jr., MS Myra & Marvin Marantz’s 50th Shirley Renders: W. D. & Judy Rose Dubrow’s 85th Birthday: Wedding Anniversary: William & Judy Ross, WA Myra & Marvin Marantz, NJ Herzberg, OR Harriet Schwartz: Edith Schwartz, Jennifer & William Egert: Phyllis Sydney Marantz: Myra & Marvin NJ Halpern, NY Marantz, NJ Molly Schwartz: Edith Schwartz, William Egert: Mollie Egert, NY Jeremy Menge: Helen Ward, NJ NJ Idan Englander’s Bar Mitzvah: Bill Michael: Henry Wiggin, MA Elsie Shurtleff: William & Virginia Brian Grodman, NH Katherine Michael’s 90th Birthday: Michael, MA Their 50th Anniversary: Robert & Carol Anne, Rosemary, & Jane Waldron, Rose Sicker: Ted Sicker & Ron Beverly Everts, MN MA Kelter, MA Agnes Farkas: Myra & Marvin Susan Milling: Mollie Egert, NY Zelma Siegel: Seymour & Barbara Marantz, NJ S. Yegna & Janet Narayan: David Regal, FL; Harold Crandus, IL, Sherwin Frank Fitzmaurice: Gerald Allee, GA; Susan Fischer, NY Korey, IL, Joseph Silverman: Miriam Moynihan, CA Stephanie O’Meara: Joseph & Mar- Brown, PA Cindy Gilman: Burton & Rona ilyn Scianna, FL Jean Edward Soldan: Linda Mason, Peck, FL; Elaine Disick, MA Jessie Pease: Patricia Tompkins, FL KS Len Gilman: Glenn Schanel, FL; Daniel Perez & Susan Speisman’s Mr. T. L. Solomon: W. D. & Judy Max & Lois Bloomfield, FL; Mark Stein, Wedding: Ann Biggs-Williams, AL; Eliza- Ross, WA FL; Mr. & Mrs. Richard O’Brien, FL; June beth Merkle, MA James G. Stout: Theodore & Meg Solomon, FL; Evelyn Sheffres, MA; Myra Susan Pogany: Anne Wilson, KS Klein, OH Blatt, FL; Gordon Bogdan, OH; Bruce Edward J. Reed: Lois Reed, NC Dr. David (Mr. Dave) Strickler: Zimmerman, FL; G. Philip Johnson, MI; Barbara Rosenblum: Molly Paul & Annabelle Closson, FL Elaine Disick, MA Saltman, CA Jean Twohey: Rose Kanter, NY Len Gilman’s 75th Birthday: Myra Jessica Ryley: Bear Creek Elemen- Blatt, FL tary School, MD; Mary Doto, NY ; Rick & The Gilman Family: Randy Leslie Frye, WA; Timothy Smith, TX; Honor Berenfield, FL Gary & Ann Schaft’s 50th Wed- Allan Baer’s 75th Birthday: Sylvia Beverly Grabow & Marvin Rose’s ding Anniversary: Stuart Cohen, NY Topp, MA Special Occasion: Bernard & Joyce Chab- Betty & Ed Schechter’s 60th Ruth Berkowitz’s 95th Birthday: ner, IL Anniversary: Betty H. Benjamin, NY; Edith Schwartz, NY Mr. & Mrs. Gussin’s 50th Anniver- Joyce Hartman, NY; Allan Kluger, PA; Corinne Bronfman’s Retirement: sary: Bernard & Joyce Chabner, IL Thomas Z. Van Raalte, NY; Rita Wolberg, Her many friends & colleagues from the Howard Haberman's 60th Birthday: PA Office Comptroller of the Currency Myra & Marvin Marantz, NJ; Edith continued on page 47 Ashley Bryan: Fontaine Laughlin, Schwartz, NJ FSH WATCH NEWSLETTER SUMMER 2005 47

Acknowledgements, continued from page 46

Eli Schindelheim’s Birthday: Eli & Schindelheim, NY Wedding Donation: Kristilyn Lank- Honey Schindelheim, NY Lois & Seymour Siegel's Birthdays: ford, PA Her son Brian: Patricia Schwartz, Zelma Siegel, IL Peter Wiese: Linda Mullins, IL NJ The Siegels: Bernard & Joyce Helen & David Younger: Rosalind Judith Seslowe: Mollie Egert, NY; Chabner, IL Devon, NY; Jane Batkin, CT Jane & Paul Rittmaster, NY Dr. Jean Staton: Sara Singer, GA Helen Younger: Sandy Batkin, NY; Janice Shulman: Seth Gelblum, NY Monti Staton: Jean Staton, GA; Elaine Rosenberg, DE Audrey Sicker: Mr. & Mrs. Schin- Ted Staton, GA; Deborah Cook, CO; Bake Sale Honoring Steven delheim, NY Louise Strickland, GA; Thomas Stewart, Zawrotny: Martin Lockheed, NJ Audrey Sicker’s Birthday: Eli NC

Thank You! The FSH Society wishes to acknowl- Dawn Young, Leader: Lynn Calmusky, ing for Research & Education Fund & edge the following for their contributions Rosanna Mossa, Dan & Sue Perez assistance in this area. to our efforts. 2004 Gala Benefit Evening Volun- Dr. David Housman, Chair, Scien- 2003 ASHG Los Angelos Booth teers: Jodi Arrabito, Bill & Ann Brooks, tific Advisory Board, for continued dedica- Hosts: Tom Dempsey, Leader; Jay Bass, Ted Fairchild, Gabriela Guadalajara, Dona tion to FSHD issues. Steve & Jane Bradford, Howard Chabner, Kahn, Janice Krajnak, Lois March, Philip Ardeth Millner & Charles Perez, Brian Dressler, Judy Herzberg, Joann Hig- & Allison Monical, Anne Robinson, Lexington, MA, for continued support to gins, Barbara Rosenblum, Michael David Segal, Yaniv Segal, David Thomp- the FSH Society office. Yanover. son. Support Group Leaders: Ann Biggs 2004 AAN San Francisco Booth Howard & Michele Chabner, CA, Williams; Lori Heater; Ann Harland; Hosts: Tom Dempsey, Leader; Emelina Fa, for fundraising efforts. Catherine l’Heureux; Linda Hoover; M.D., Frank Fitzmaurice, Jill Fleischer, Paul Closson, Fl, for hosting the Becky Howell; Karen Johnsen (deceased); Karen Myers. FSH Society Bulletin Board & chats. Carol Perez; Dawn Young. 2004 ASHG Toronto Booth Hosts: Bill & Judy Herzberg, OR, fundrais-

FSH Society Fact Sheet The FSH Society is an independent, weaknesses often provide a clue to the through education of the general public, 501(c)(3) non-profit and tax-exempt U.S. physician that distinguishes this disease governmental bodies and the medical pro- corporation organized to address issues from other neuromuscular diseases that fession; and needs specifically related to FSHD. can be similar in appearance. to support such research and devel- Papers certifying its incorporation, bylaws The age of onset is variable as is the opment through solicitation of grants and and tax-exempt status are deposited at the eventual extent and degree of muscle loss, contributions from individuals, private corporation's east and west coast offices but noticeable muscle weaknesses are usu- foundations, the pharmaceutical industry and the office of its general counsel in ally present by the age of twenty and are and others Washington, D.C. recognizable in all but a small percentage to accumulate and disseminate FSHD is a muscle disease with a fre- of adults who carry the gene. The progno- information about FSHD; quency in the population of between 4 and sis includes both a loss of muscular to actively cooperate with related 10 per 100,000. The disease is inheritable strength that limits personal and occupa- organizations and foster communication and the responsible gene is located on tional activities of most FSHD individuals among all interested parties; and chromosome 4. The expression of symp- and a loss of mobility in perhaps twenty to represent individuals and fami- toms requires inheritance of the defective percent of the cases. Hearing loss and reti- lies with FSHD. gene from only one affected parent, and nal abnormalities associated with FSHD The Society invites contact from any an individual of either sex has a fifty per- have been reported, but the frequency of interested individuals, families, physicians, cent chance of inheriting the gene from these effects and their relationship, if any, caregivers, charitable organizations, gov- that affected parent. to the causative gene for the muscle defect ernment agencies, industry, scientific The major consequence of inheriting are uncertain. researchers and academic institutions. Any the disease is that of a progressive loss of The FSH Society was created because inquiries regarding membership, charitable skeletal muscle, with a usual pattern of ini- of a need for a comprehensive resource for donations, purposes and goals or other tial noticeable weakness of facial, scapular FSHD individuals and families. Purposes issues pertaining to the Society and FSHD, and upper arm muscles and subsequent of the organization are: should be addressed to the east or west developing weaknesses of other muscles of to encourage and promote scientific coast offices. the torso and lower limbs. Early facial and clinical research and development FSH Society Membership Application—Donation

Name(s) ______Address ______City/State/Zip ______Phone: Day ( )______Evening ( )______E-mail: ______

Use space below for address changes, specifying interested individual, specifying title and affiliation, corpo- rate designation or for any other comments you may have: ______Individual Membership Organizational Membership Regular Member $35.00 + Corporate I $1000.00 + Sustaining Member $70.00 + Corporate II $2500.00 + Patron $100.00 + Corporate III $5000.00 + Sponsor $250.00 + Donor $500.00 + Non Membership Donation Benefactor $1000.00 + Other $ ______ Other $ ______Research & Education Fund Donation Other $ ______Professional Membership Regular Professional Member $100.00 + Total enclosed $ ______ Sustaining Professional Member $200.00 + Please check here if you would like your Associate $500.00 + membership or donation acknowledged in Fellow $1000.00 + the next issue of the FSH newsletter.

Bill my Credit Card: AMEX VISA MasterCard Discover Account No. ______Card Expiration Date (MM/YY) ____/____ Repeat the Contribution Amount? ____ Monthly ____ Quarterly ____ Semi-Annually Signature: ______

Contributions to the FSH Society are tax-deductible and acknowledged for tax purposes. Please make checks payable to the FSH Society and send contributions to: Carol A. Perez, Executive Director, FSH Society, Inc. 3 Westwood Road, Lexington MA 02420 USA. Please Note: Checks or money orders from outside the United States should be in US dollars from institutions with US bank affiliations.

FSH Society FIRST CLASS MAIL 3 Westwood Road U.S. POSTAGE Lexington MA 02420 USA PAID CHELMSFORD, MA PERMIT NO. 105