Star light, star bright, First star I see tonight I wish I may, I wish I might Natalies Wish Have the wish, I wish tonight. ’ ★ FOR FRIENDS OF NATALIE STACK AND SUPPORTERS OF THE CYSTINOSIS RESEARCH FOUNDATION FEBRUARY 2006

Dear Friends and Family In February 2003, on Natalie’s twelfth birthday, she shared her secret wish with me: “To have my disease go away forever.” Because of all of you, that wish is one step closer to becoming a reality. Our fourth annual Natalie’s Wish event on June 2, 2005 was an extraordinary success. This amazing evening began with best-selling author and journalist, Morton Kondracke sharing the story of his late wife Milly’s courageous battle with From Natalie Parkinson’s disease. Mr. Kondracke emphasized the need for funding medical research especially

❖ for orphan diseases like Cystinosis. ❖ I started 9th grade in September. I recently started ❖ After Mr. Kondracke’s presentation, we watched ❖ playing basketball for my high school JV team. So far, in amazement as our first live auction raised ❖ ❖ it is my favorite part of high school! $98,000 for Cystinosis research. Following the auction, the highlight of the evening was Last year, I started a new medication for my eyes. In October I had an appointment the Fund-A-Cure segment where we again were at the National Institutes of Health (NIH) in Bethesda, Maryland. I met with Dr. Tsilou astonished as more than $290,000 was donated for because my eyes always felt itchy and sometimes it felt like I had an eyelash in my research. By the end of the night, over $825,000 eyes even though I didn’t. Dr. Tsilou is the doctor who examines the eyes of kids was raised for Cystinosis research. 100 percent with Cystinosis. I had an early morning appointment at the NIH. They examined of every dollar donated to the Cystinosis my eyes, dilated them and took pictures of the crystals covering my corneas. Research Foundation goes to Cystinosis research. All costs of the event and day-to-day The doctor saw lots and lots of cystine crystals in my eyes. That was not a good costs of the foundation are completely underwritten. thing because if more crystals form, I could lose my eye sight or damage my In 2005 alone more than $1,146,000 was raised corneas. That would be awful and it would make it hard to live a normal life. for research! When I found out that I could go blind if I did not take the eye drops, it scared me and I knew I had to use the eye drops every day. We could not do this without all of you. The doctors told me that I had to take the eye drops 8 –12 times every day or else Your outpouring of love and support the cystine crystals would keep forming in my eyes. If I don’t take them regularly has been invaluable. the crystals won’t go away. If I take the drops all the time, the crystals will eventually dissolve but the hassle is that I have to take them every day forever. I am glad there We cannot thank you enough for your support in our are eye drops and I have a treatment. I have learned to take the eyedrops by myself. efforts to find better treatments and ultimately a cure Thank you everyone for making such for Cystinosis. Your support has allowed us to fund a number of multi-year research studies, something a difference and helping all of us with that had been impossible in the past due to lack of Cystinosis have hope for a better future. long-term funding. Currently there are six research studies underway and one study being reviewed and pending approval by the Scientific Review Board. We look forward to making an announcement soon!

Alex and Natalie Stack continued on page two BOMA Golf Tournament for I am inspired by Cystinosis Research Foundation my good pal Natalie... For the second year in a row, the Building Owners and Managers Association (BOMA) of Orange County chose the Cystinosis Research Foundation as the beneficiary of their Annual Charity Golf Tournament in August, 2005. The tournament sold out with 144 participants. David Martin The live and silent auction raised over $9,000 for the Foundation. We are grateful to our friends at BOMA-OC. Special thanks to the Tri-ing to committee who worked so tirelessly: Bob Brans of Structural Materials, John Czorniak of Pacific Building Care, Diana Dean of Environomics Find a Cure West, Tom Devlin of Allied-Barton Security Service, Dale Fedele of Ampower, Seth Foster of HSG/Birdbusters, Lynn Infurchia of Belfor for Natalie USA, Jeff Koscher of Advanced Restoration, Lisa Miller of CarrAmerica Realty Corp., Monique Mora of the Gale Company, Betty Pickett of All of us have ideas about certain limitations Universal Protection, Mike Raring, AAA Electrical & Communications, and restrictions and what we can and cannot do. Often we hear “shouldn’t” Jon Schneider of Specialty Uniform Services, Eric Sorensen of Able and “couldn’t” and use those terms for not trying at all. I am inspired by Engineering, Brett Wells of Frazee Paint and my good pal Natalie who rejects those negatives and says “Yes I can.” Robin Jochims of BOMA-OC. Thank you! So in spite of the “shouldn’t” and “can’t”...I “could” and “did” complete the Lavaman Triathlon in Hawaii. Again spectators asked “who is Natalie?,” The 2006 BOMA-OC Charity Golf Classic “What is Cystinosis?” I was so proud to share Natalie’s wish. will be held August 2, at the Talega Golf Club in San Clemente. For details Thank you Natalie for allowing me to share your story visit www.natalieswish.org/events. and represent the Cystinosis Research Foundation.

Dear Friends and Family continued from front page

The Cystinosis Research Foundation (CRF) is the largest nonprofit refrigerated and must be taken every funder of Cystinosis research. As of 2003, the CRF has funded more waking hour a minimum of eight times than $1.5 million supporting seven Cystinosis Research projects. a day. The drops dissolve the crystals but This year more than $895,000 is available for Cystinosis research they must be taken for the rest of her life or the crystals will reaccumulate. projects. We will soon announce to the medical and scientific Although the eye drops sting and smell, Natalie has learned to take them communities that we are accepting grant proposals. On June 1, herself. We are grateful there is a treatment and that she is able to tolerate it. during our Natalie’s Wish event, we will announce which research It is not just our family that is so thankful. We receive letters from other studies will be funded in 2006. families who have children affected by Cystinosis. So many of their children We are continually amazed at how blessed and fortunate we are to are very ill and suffering every day. They thank us for the new and continuing have such a wonderful community of family and friends. We could research funded by the CRF. It is because of all of you – our community of not do this without all of you. Your outpouring of love and support friends and family that have made a difference. So, on behalf of all of the has been invaluable and we treasure every letter, email and note families with Cystinosis, we are eternally grateful for your continued support we receive. Your prayers have made a difference – we are moving as we move closer to improving and prolonging the lives of our children. into the next clinical phase of the slow-release medication study. Your financial support has provided Natalie and others with Cystinosis the Research is slow but we are continually learning new and important hope they so desperately need. We thank you for your commitment to our information about Cystinosis. It is a time of hope! cause. We are also grateful to the many volunteers who made our Natalie’s Although Natalie looks healthy on the outside, inside she is not. Wish event such a success. We are especially thankful for the tireless efforts In October we visited the NIH because she was experiencing pain of Zoe Solsby and Marylyn Milburn. and discomfort in her eyes. The exam revealed that Natalie’s corneas We hope that you will join us for this year’s Natalie’s Wish event on Thursday, were covered with cystine crystals. Accumulation of the crystals June 1, 2006 at the Balboa Bay Club in Newport Beach. The evening promises causes photophobia and pain similar to the feeling of having sand in to be inspirational and uplifting with Kevin Sharp, an award-winning vocalist your eyes. Although the news was not good, it was not unexpected and speaker, sharing The Power of A Wish – his story of hope and survival. given the inevitable progression of Cystinosis. Fortunately, there are We look forward to seeing you there. experimental eye drops available as a treatment. We are now in our fourth month of eye drops. To be effective, the drops need to be Nancy and Jeff Stack Feature on Sigma-Tau “What’s the difference between a disease affecting 300 and 300,000,000? To us,nothing. At Sigma-Tau Pharmaceuticals, Inc., our mission is to help ensure patients with rare diseases are not left untreated.We are dedicated to providing new therapies and new hope for patients with rare diseases.”

GREGG LAPOINTE, CHIEF OPERATING OFFICER, SIGMA-TAU PHARMACEUTICALS, INC.

Laura’s a Picky Eater Laura’s success with her treatments was due to the dedication of her Marybeth knew that there was something wrong with her daughter Laura parents, clinical researchers and almost from birth. She was a picky eater with cravings for salty and spicy companies like Sigma-Tau, who are food, and she was so tiny for her age that her measurements didn’t make it dedicated to research for treatments for rare diseases like Cystinosis. on to the growth charts. But it wasn’t until her second birthday – after being Laura’s participation in the clinical study, helps other children with admitted to the hospital for severe dehydration following the flu – that doctors Cystinosis be assured that there is hope. finally consulted Dr. Frederick Kaskel, a pediatric kidney specialist. As soon as he heard Laura’s story, Dr. Kaskel suspected Cystinosis. Laura’s Life Is Looking Up for Jack parents weren’t aware at the time, but he had recently attended a lecture by Dr. William Gahl of the National Institutes of Health, who had described Can you imagine watching a three-year-old child guzzle an entire 20-ounce Laura’s problem. After a battery of tests, Dr. Kaskel confirmed Laura’s bottle of water in one gulp? Or watching your son vomit up everything he diagnosis of Cystinosis, and her parents were on the phone talking to eats? His parents, Christy and Dave can. Dr. Gahl, who had dedicated his life’s work to this rare disease. When he was born, Jack was a big, happy baby who ate, cried, slept and After the conversation, Laura’s parents knew they were in capable hands. played much like his older sister. As he grew, however, instead of walking Marybeth recalls, “Instead of saying, ‘Don’t worry about her, she’ll probably like other kids, Jack continued to scoot across the floor on his bottom. His outgrow this’, he asked questions and listened to my answers.” She learned that parents also noticed that he drank a lot and went through a lot of diapers. Cystinosis is an inherited metabolic disease that results in an abnormal But he was a big baby, so his parents just assumed it was because of his size. accumulation of the amino acid cystine in organs of the body. This can When Jack stopped eating and started vomiting regularly his parents knew that cause many serious complications. An oral treatment called Cystagon® can something was wrong. Visits to their pediatrician led to consultations with help manage the crystal accumulation in all the organs except the eye. gastroenterologists, geneticists, nephrologists and ophthalmologists. As a Tiny crystals of cystine begin to develop result, his parents, Christy and Dave, got a crash course in obscure diseases. in the cornea and cause hypersensitivity Since that diagnosis at one-year-old, perspective became the battle cry of to light that Laura experienced. The tiny their daily lives with Cystinosis, and the word ‘normal’ has taken on new specks shown in the bar of light are meaning. Jack now has a gastric feeding tube in his stomach through which corneal cystine crystals – the result he receives liquids, nutrition and medicine. He’s also taking a number of of cystine build-up. medicines to manage his disease. Jack’s everyday, six-hour medical routine Not long after meeting Laura and hearing her story, Dr. Gahl asked Marybeth has enabled him to grow surprisingly well, and allowed him to become to enroll her in an eye drop protocol study of children with Cystinosis being one of the healthiest of all kids with Cystinosis. conducted at the NIH. Since then, and for most of her life, Laura has been But despite the lifelong medication regimens and challenges of preparing involved in testing the experimental eye drops. for an independent adulthood, patients like Jack can be confident that The eye drops are being developed by NIH with support from Sigma-Tau others will continue researching this disease to add to the knowledge and Pharmaceuticals, Inc. Sigma-Tau is dedicated to researching and developing understanding of how to better manage it, while offering hope to others. treatments to improve the lives of patients and families living with rare Dedicating resources to the NIH research is just one way that Sigma-Tau diseases. Simply because it’s the right thing to do. demonstrates its commitment to rare diseases. Sigma-Tau has supported Laura does not want to draw attention to her condition, thus the challenge patients with these diseases since 1985, when it became one of the first of getting a busy young adult to administer the eye drops on a regular basis. companies in the world to obtain an Orphan Drug approval in the United The road has not been easy. Every four months for much of her life, Laura States. To Sigma-Tau, there is no greater accomplishment than helping returned to the NIH for monitoring and medication adjustments. people with rare diseases. Its mission is to help ensure that patients with rare diseases are not left untreated. Now 20, Laura is a normal, young adult. Early on, her family developed a philosophy for living with the disease: “We can’t change what you have,” Sigma-Tau Pharmaceuticals, Inc., is one of those rare companies dedicated her parents told her, “we have to learn to live with it.” to discovering new therapies for patients with rare diseases. Birthday Wishes

Fourteenth Birthday Party Benefits Cystinosis Research Foundation

Kelsey Valley, Shelby Searles, Jenny Madden and Caroline Kelter, four Harbor Day School 8th graders, who have been Natalie’s classmates for nine years, decided to celebrate their fourteenth birthdays with a party to benefit the Cystinosis Research Foundation. On Friday, May 27, 2005, Memorial Day weekend, the girls boarded the TIKI boat out of the Balboa Fun Zone with 45 classmates and seven brave Moms. They toured the harbor for five hours while dancing to the sounds of a DJ from Los Angeles who played their favorite songs. In lieu of gifts, the girls requested that guests write a check to support Natalie’s Wish and by the end of the evening they had raised $6,415! The girls were so thrilled they thought about making this an annual event to help Natalie’s wish come true.

Ava’s First Birthday Birthday By Renee C Kirsten’s Eighth arter – Ava’s Mother g nsen wanted to do somethin On April 2, 2005 our daug hth birthday party, Kirsten Ha hter Ava For her eig e theme. turned on a theatre party, with a Greas e year old. A milestone – special. She decided to have and her guests in a a time to reflect on the actress/director lead Kirsten wonderful A professional e end progr in 50’s era costumes. At th ess in her young life– and fo earsal and then dressed them r reh the musical Grease us, a time to hon performed a short version of or our dear friend of the party the girls . , this was not the special part and a true inspiration, Nata arents and families. However lie for their p guests each Stack. Wh to the party, Kirsten and her en our son, Nathan, had Instead of bringing presents rch Foundation. his first birthday in Aug ution to the Cystinosis Resea ust of 2003 made a contrib we re ted quested “no gifts.” We also chool family and Kirsten wan asked that if guests felt as in Kirsten’s Harbor Day S compelled to gi Natalie w th year. More ve something, they make a d r her during their 8 grade onation on his to do something special fo behalf to the Cystinosis Re a wonderful time. search Foundation. s raised and the girls all had than $1,000 wa We c ontinue to believe the best g ift we can give our children is the willingness to share th eir blessings of good health and good fortune w ith those who are less fortun re ate. For this ason, we chose to jointly cel ebrate the life our youngest child, Ava, and the lif e of Natalie and others with We Cystinosis. are honored to include Nata lie and the entire Stack fami among our mo ly st celebrated of friendships. Ava’s party was wond erful. The In-n-Out Burger t our ruck served guests; a princess castle jum per provided a fun outlet for the kids; and a face painter and balloon twister topped o day. A day ff the that we’ll always remember! 6 Questions for Lynette and Michael K. Hayde

❶ How did you first learn about the Cystinosis Research Foundation? Mike and Lynette knew for many years that Natalie Stack had a rare disease. But they never approached Jeff or Nancy about it because they did not want to intrude or cause them any more pain than they were already living with. They did, however, respond to an invitation to attend a Natalie’s Wish event where they first learned about Natalie’s disease. It was a tough evening for them and for everyone who attended. Mike and the gentleman he sat with “were in tears” much of the evening. ❷ You know the Stacks personally and professionally. Is that why you first became donors? Are there other reasons you continue to be so committed? Mike has known Jeff for more than 20 years. They are friendly yet fierce competitors in the apartment business. But they have a great deal of respect for each other. Their business relationship is almost certainly what got Mike and Lynette to attend that first event. “We became donors because we were deeply touched as we listened that night,” Lynette said. While Mike had an initial gift in mind, Lynette immediately rejected it and said, “We have to do more.” Lynette is a compassionate person who believes in miracles. She also believes, “that if the mind can conceive it, then it can become a reality. As long as we are able, we will work to make Natalie’s wish come true.”

❸ With your extensive expertise in the nonprofit world, what distinguishes the Cystinosis Research Foundation from other nonprofits? Are there other organizations that have a fundraising approach similar to CRF and its commitment to good stewardship? Mike and Lynette decided long ago they would spend most of their time and money helping children because “they are the future.” “We give to many important causes, but most of the time we don’t personally know those who benefit from our giving. The Cystinosis Research Foundation presented us with a unique opportunity. Of course we understand the benefits for those who are affected by this terrible disease. But in this case we personally know someone who suffers from Cystinosis. Natalie is very special to everyone who knows her. This makes this quest extremely personal.” ❹ Cystinosis is a rare disease affecting only a few hundred children in the United States. How big a role does that play in your commitment to the organization? “If not all of us, then who will take on this challenge?” asks Lynette. It is clear that the major pharmaceutical companies cannot or will not do research on a disease if the market is so small it will not generate a profit. While most of us don’t fully understand or even agree with this reasoning it seems that “it’s up to us to make a start. We hope the Cystinosis research we’re helping to fund will provide crossover benefits for other diseases. Then the market may be large enough to entice a major pharmaceutical company into the fight.” ❺ As advocates for Natalie’s Wish, what would you say to others to encourage them to be involved? “We all have our favorite causes,” but Mike and Lynette still ask their friends and colleagues to help Natalie. “This courageous young lady knows her life expectancy is short but she is still filled with joy,” Lynette says. Mike and Lynette are convinced they can make a difference, and they encourage others to help as well. “If someone can look at Natalie and other children with Cystinosis and turn away, there is nothing more we can say to convince them to help,” she adds. ❻ You have made a large financial contribution to the CRF for Cystinosis research, what are you thoughts? “Some would say that there’s not much chance of the research being successful, but we like siding with the underdog,” Mike says. An American president once got school children to collect dimes to find a cure for polio. It was a dreadful disease and seemed unconquerable. But in his youth Mike was part of that effort. Today, when the vaccination is given there is no polio. Now Mike boldly adds, “We will support Cystinosis research until we find the cure.” Committed to Making a Difference

2005 Donor List Donor List

$50,000 AND MORE $2,500 AND MORE Lynette and Mike Hayde Randolph and Judith Agley Jim and Jennifer Damon Roberta and Jerry Dauderman • Amies Communications Sisters Sarah, age 22, SARES REGIS Group Dianne and Richard Azar Yvette del Prado and Katie, age 20 Nancy and Jeff Stack Carol Cranfield Draper Family Foundation Fund Louise and Peter Donovan Anne G. Earhart Dzida, Carey & Steinman Steve and Susie Duffy, Dick Eddy $20,000 AND MORE Jeff and Stacy Stone Western National Realty Advisors Ray Eldridge Sheri and Chris Dialynas Janet and Jim Stoneman Linda and Kris Elftmann Bob Elliott Barbara and John Stuart Equity Residential Foundation J.P. Morgan Chase Rick Emsiek Style Interior Design David and Suzu Neithercut Darby T. Keen Gail and Dale Fasse/RK Advertising Marilyn and Tom Sutton Mary Ann King Favreau Engineering, Inc. Marcy and Gerry Spector Kyle and David Team Dale Kistler and Sue Murahata Patti and Ed Feldman Cassie and Jim Thomas Ginni and Kent Valley Karen and Tom Linden Janet and Frank Foster Leslie and Will Thompson Eric Luna Franciscan Friars Gary and Marlene Tolfa $10,000 AND MORE Makar Properties, LLC Fuscoe Engineering, Inc. Nina and John Townsend Gerson and Barbara Bakar Robert and Nancy McLeod Edward J. Geraghty Dr. M. Vellard and Dr. E. 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Bob and Bunny Perlberg LNR Property Robert DeWitt Anne Marie and Bob Couglan Yvone Perlberg/AMGEN FOUNDATION John and Janice Markley Stephanie and Bruce Dorfman Ron Cox James M. Peters Barbara and Bill Driscoll Karin Krogius and Scott Mason Diane and Gene Crain Robert C. Ruocco Jerry and Gail Durkin Steven Myers Kim and Dick Crawford Denise and Patrick Russell Diane and John Erskine Chrissy and Rick Nicholas Doug and Cindy Crocker John Schaefer Michael S. Fallman Sue Ellen and Paul O’Connor Rick Scherrer Dennis Schmucker Fieldstone Foundation Steve Quinn and Pam Bellamy Tom and Jill Schriber Malin Fletcher Regis Homes of Northern California Leslie and David Seidner Bill and Marcia Gaboury Rob Wagner & Mark Kroll Shapell Industries, Inc. Caroline and James Gapp Gary Ryness Lauren and Bob Silvernail Stephanie and Jim Gilly Janet Keller and Bernie Schneider Melvin and Bren Simon Russell and Donna Goodman Zoe and Don Solsby John and Judy Goolsby Christine and Bill Thormahlen Sheila and Ygal Sonenshine David and Ruth Green The Ryland Group Steve Stambaugh & Elena Cappadona Larry and Debbie Green Sheila and Ted Weschler Janet and Mike Starzyk Tricia and Mark Haarer Hugh, age 4, diagnosed prenatally For more information about Cystinosis, visit www.natalieswish.org.

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Finn Patty and Bruce Tester Leslie Shattuck Gwenn and Don Abrams Katie Stack Natalie Fitzpatrick The Arches Restaurant Olive Stephens on behalf of Katie Stemler Susan and Tim Strader Joanne Fix Deborah and Bart Thomsen Sallie Jane and Greg Super Bob and Roberta Barry, Doris Trauner and Richard Stanford Warren, Sherry and Nicole Fix Louise Upham Cheryl, Nils-Eric and JBA Facility Planning Socorro and Ernesto Vasquez The Flattum Family Jane and Kenneth Valach Christopher Svensson Laura Beuerlein Monique von Lutzow Kevin Forsyth Barbara and Elliott Wagner James and Madeline Swinden Thomas and Barbara Bozzuto Julie and Mike Winter Nadyne Foster Marnie Wickert Jay and Ann Thornton Mr. and Mrs. Ernest R. 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Corinne Antignac, MD, PhD in which the mouse gene has been inactivated. strains and are currently analyzing the mice Hospital Necker-Enfants Maades, Paris, France These mice present elevated cystine levels, for kidney, behavioral, bone and ocular even at birth, which increase with age. changes. In addition, in collaboration with Our laboratory is located at Necker Hospital Furthermore, cystine crystals were present Dr. Minnie Sarwal at Stanford University, we in Paris, where there is a long history in in various organs from the age of six are comparing the gene expression patterns the Department of Pediatric Nephrology of months. These mice do not develop any between normal and Cystinosis mouse treating children with Cystinosis. We started obvious renal phenotype. In contrast, from tissues to identify key cellular pathways working on Cystinosis in 1995, when the 6– 8 months of age, they show decreased either altered in Cystinosis or, on the chromosomal localization of the gene on activity and osteoporosis, as well as ocular contrary, involved in the protection of the chromosome 17 had just been found by lesions similar to those in patients, making cells. This could explain the lesser severity the International Cystinosis Consortium. We them a good model to study the mechanisms of the disease in the mouse model, and then identified the gene underlying Cystinosis in be exploited in the long term to develop of cystine accumulation and to test new 1998, in collaboration with Dr. W. van’t Hoff new therapeutic strategies. treatments to decrease the cellular and Dr. M. Town in London. We subsequently concentration of cystine. Another very exciting field of our research, showed that cystinosin, as they named the currently funded by the Cystinosis Research Our current research projects are aimed at Cystinosis gene product, was indeed a specific Foundation, is the study of the role of understanding the exact role of cystinosin transporter of cystine located at the membrane cystinosin at the cellular level. We have in the cells and why its alteration leads to of the lysosomes. We also characterized several reasons that make us think that the development of Cystinosis. We are using mutations in the Cystinosis gene in almost cystinosin might also have a role in cystine both our animal model and cellular models 150 children from all over the world. This transport in the lysosome. We are currently we have recently developed in the lab. allowed us to correlate the severity of the trying to demonstrate it using cell lines we disease with the type of mutations and The severity of the disease in the mouse have generated stably expressing cystinosin identify key regions in cystinosin. Since varies depending on the strain of the mouse. (normal or mutated) tagged with a no animal model of Cystinosis existed, Thus, we have transferred the mutation of fluorescent marker, which renders it easily we generated a knock-out mouse model, the Cystinosis gene onto two pure mouse detectable under a fluorescence microscope.

Ranjan Dohil, MD absorbed into the blood stream and once that a controlled-release cysteamine therapy Associate Clinical Professor absorbed, how much is metabolized by the would be possible. We are excited about the Division of Pediatric Gastroenterology liver as soon as it has been absorbed. next phase of our study, i.e., creating the and Hepatology, UCSD School of Medicine In addition to testing CystagonTM, we will also actual controlled-release therapy and testing Pharmacokinetic evaluation of cysteamine evaluate cystamine. Cystamine is an odorless patients with Cystinosis. We recently received bitartrate (CystagonTM) and cystamine compound, which consist of two cysteamine a commitment from Mylan Laboratories, Inc., molecules and the results of the study will the current provider of CystagonTM, to provide TM When Cystagon was approved in 1994, the help us assess if cystamine could be used as the medication necessary for this study. FDA did not require information about the a pro-drug. The advantage of a pro-drug may We appreciate their participation in helping absorption, metabolism and distribution of be a reduction of gastrointestinal side effects to move this study forward. CystagonTM (cysteamine bitartrate). While it as well as the avoidance of the unpleasant was initially seen as a benefit that the FDA body odor CystagonTM causes. Cystamine is did not require this information before potentially a therapeutic option for the future. CRF is pleased to report that the results approving CystagonTM, this lack of knowledge In the meantime, however, we are focused on of Dr. Dohil’s absorption study will be is now limiting the development of an creating a new method of delivering CystagonTM. published in the Journal of Pediatrics improved way to administer the drug. The within the next few months. Once Controlled-release Cysteamine Therapy. aim of the animal study we have designed published it will be posted on our is to evaluate how much of the drug is Results from our initial study would suggest web site at www.natalieswish.org. Progress Report: Mitchondrial showed myopathic changes, with decreased Because of your generosity to the amplitude and duration of motor unit action Dysfunction in Cystinosis Myopathy potentials, and numerous polyphasic potentials. Cystinosis Research Foundation Doris A. Trauner, MD Two patients had neurogenic changes, one in addition to myopathic changes and one we have funded and committed Professor, Departments of Neurosciences without myopathic changes. and Pediatrics; Chief, Pediatric Neurology nearly $1,600,000 in Cystinosis D. Metabolic studies: Two-thirds of the patients UCSD School of Medicine had low or borderline low plasma Co-enzyme research.This makes the CRF Aims of the study: Q 10 levels. The same percentage had elevated The specific aims are to determine whether the blood CPK levels, suggestive of muscle damage. the largest nonprofit funder of myopathy associated with nephropathic Cystinosis All had normal muscle carnitine levels. These Cystinosis research in the world. is the result of mitochondrial dysfunction with findings add to the pathological data and resultant deficiency in respiratory transport suggest that muscle may be involved in Cystinosis even without evidence of clinical chain function in adolescents and adults with Corrine Antignac, MD, PhD Cystinosis, and to determine if a treatment symptoms, and the low Co-enzyme Q 10 Hospital Necker-Enfants Maades, regimen that provides additional co-factors for levels suggest that the muscle problem may these enzymes will improve the strength and be the result of mitochondrial dysfunction. Paris, France prevent deterioration in muscle strength. E. Exercise testing: Results of exercise testing 2005 - $78,000 on all of the patients have not been analyzed Ranjan Dohil, MD Progress to date: yet, because the blinding in terms of placebo Associate Clinical Professor ❶ Enrollment vs. mitochondrial “cocktail” has not been broken. We will conduct those analyses at Division of Pediatric Gastroenterology Eleven patients (age range 16– 43 years) have the completion of the 12-month studies. and Hepatology, been enrolled in the study. One was unable to School of Medicine continue because of prior participation in a Future plans study of cardiac function. Of the remaining ten, University of California, San Diego, ❶ Complete 6- and 12-month testing. one has completed the 12-month visit, eight 2002–2005 - $338,542 ❷ have completed the six-month visits, and Enter new patients as they are identified. 2005 - $200,000 We would like a total of 20 patients. one has completed the first visit. All patients Thomas Jeitner, PhD have been randomized to treatment with a ❸ Analyze data and write manuscripts Research Assistant Professor, “mitochondrial cocktail” or placebo. The code with results of study. has not yet been broken to determine which Department of Biochemistry, patients have received which regimen. Medical College of Wisconsin A Study of the Cognitive Domain of Executive 2004 –2005 - $92,680 ❷ Results of study to date Functioning in Individuals with Cystinosis A. Symptoms of myopathy: Only three of 11 patients Dzung H. Nguyen, PhD complained of weakness and/or chewing and Amy M. Spilkin, PhD Assistant Project Scientist swallowing difficulties. No patient under the age Principal Investigator Ajit Varki Laboratory, School of Medicine, of 25 had a history of weakness or easy fatigue. Glycobiology Research and Training Program, B. Muscle biopsy: 11 muscle biopsies have Angela O. Ballantyne, PhD University of California, San Diego been performed. Six had abnormal findings Co-Investigator 2005 - $127,000 on light microscopy. These included fiber Progress to date: Over the first six months we Amy Spilkin, PhD size variation, myofiber atrophy, ring fibers, obtained Institutional Review Board approval endomysial fibrosis, vacuolar inclusions, Assistant Project Neuroscientist for the study, ordered supplies, and trained Pediatric Neurology Research Group increase in red granular staining with trichrome, a research assistant on the measures to be increase in lipid droplets with oil red O, and administered. In addition, we have successfully University of California, San Diego type II fiber atrophy. One additional muscle recruited, inducted, and tested 14 individuals 2005 - $167,865 biopsy was not diagnosed as abnormal, but with Cystinosis and 2 control participants. Jess G. Thoene, MD there were findings suggestive of mild type II Hence, we have made substantial progress Director, Hayward Genetics Center, fiber atrophy and increase in size of lipid toward the goals of this study. droplets. Electron microscopy of the muscle Karen Gore Professor Pediatrics, was available for seven patients. Only two were Results: On all 16 participants to date, we have Tulane University, School of Medicine read as normal. Abnormal findings included collected D-KEFS, Wechsler IQs, and the age- 2002 - $100,000 filamentous bodies, ring fibers, occasional appropriate executive functioning questionnaires 2003 - $105,000 mitochondrial degeneration, and tubular (BRIEF or FrSBe). We have also scored, 2004 - $75,000 reliability checked, and data entered all of the intracytoplasmic inclusions. These abnormalities 2005 - $200,000 were present even in patients who had no test and questionnaire data collected so far. complaints of muscle weakness, and who Since we are in the first quarter of this study, Doris A. Trauner, MD had good strength on muscle testing. Thus, we have not yet analyzed any of the data. Professor, Department of Neurosciences, myopathic changes in the muscle can be found Future plans: In the next six months, we plan to University of California, San Diego even in asymptomatic patients with Cystinosis. continue to recruit, induct and test individuals 2004 - $97,300 C. EMG/NCV: We have received reports of six EMG with Cystinosis and matched control participants, and NCV studies to date. Two patients had as we work towards the projected participants As research updates become available they normal studies (20 and 21.5 years old). Three (i.e., 30 with Cystinosis, 30 controls.) will be posted at www.natalieswish.org $772,986 The Power of a Wish in Research Funded through We are excited to announce that Kevin Sharp will be the guest speaker 2005 Natalie’s Wish Event at our Fifth Annual Natalie’s Wish Fundraiser on Thursday, June 1, 2006 at the Balboa Bay Club in Newport Beach, California. Kevin Sharp, award-winning vocalist, entertainer and cancer survivor, will inspire us all as Corinne Antignac, MD, PhD he shares his experiences and the lessons he learned while battling cancer. The foundations Hospital Necker-Enfants Maades, Paris, France of his strong beliefs are never giving in and never giving up. Kevin knows the most powerful “Characterizations of Cystinosin gift we have in this life is – HOPE. Intracellular Trafficking” $78,000 – 1-year study As a teenager, Kevin was a gifted athlete who excelled in several sports. He began experiencing Ranjan Dohil, MD fatigue and unexplained pain in his leg, which was later diagnosed as a rare form of bone cancer (Ewings Sarcoma) that had spread to his lungs. University of California, San Diego, “Clinical Studies of Cystinosis: As a senior in high school, Kevin was told that his chance of survival was slim. Uncertain if he Attempts to Improve Treatment” would live six months, Kevin was introduced to the Make A Wish Foundation, which grants wishes $200,000 – 2-year study to children with life-threatening illnesses. They honored his wish of meeting producer/ Dzung H. Nguyen, PhD performer David Foster, whose friendship sustained Kevin through two grueling years University of California, San Diego of chemotherapy, experimental drugs and radiation treatments. It also opened “Development of a Rapid Method of a door for Kevin to pursue his goal to become a successful country artist. Neutrophil/Monocyte Isolation of the To everyone’s surprise, Kevin went into remission in 1991. He has never Diagnosis and Monitoring of Cystinosis” forgotten the generosity of the Make A Wish Foundation, and currently $127,121 – 2-year study acts as a national spokesperson for the group. He was also honored with Jess G. Thoene, MD the prestigious Wishgranter of the Year Award, which singled him out (On hold due to hurricane Katrina, for the devotion, dedication and inspiration he provides the children. research lab destroyed) To date, Kevin is the only “wish child” to become the wish request of other Tulane University, School of Medicine wish kids, making his wish experience come full circle. “Lysosomal Cystine Enhanced Apoptosis in Cultured Human Mesenchymal Stem Cells” A platinum debut album, Measure Of A Man; scores of award nominations; $200,000 – 2-year study and a string of chart-topping hits including She’s Sure Taking It Well, If You Love Somebody, and the highly acclaimed Nobody Knows– which held the Amy Spilkin, PhD top spot on Billboard’s Country Singles Chart for an astonishing four weeks – University of California, San Diego mark his debut as the best by a new male country singer in five years. “A Study of the Cognitive Domain of Executive Functioning in Individuals with Cystinosis” Kevin is a living example of the power of a wish and we are blessed to have him $167,865 – 2-year study share his music and his story with us at Natalie’s Wish on June 1, 2006.

I wish I may, I wish I might, have the wish I wish tonight.

CYSTINOSIS RESEARCH FOUNDATION PRESORTED STANDARD U.S. POSTAGE 18802 Bardeen, Irvine, California 92612-1521 PAID 949.809.2400 • www.natalieswish.org SANTA ANA, CA PERMIT NO. 3 501(c)3 Federal Tax ID #32-0067668

❖ Save the Date ❖ ❖ ❖ THE FIFTH ANNUAL ❖ ❖ “NATALIE’S WISH” FUNDRAISER ❖ ❖ ❖ THURSDAY, JUNE 1, 2006 ❖ ❖ ❖ ❖ ❖ ❖ ❖ Newport Beach California ❖ ❖ FOR INFORMATION VISIT WWW.NATALIESWISH.ORG ❖