RESEARCH HIGHLIGHTS | NEW IPPF OUTREACH MANAGER | ADVOCATING ON CAPITOL HILL
QuarterlyJournal of the International Pemphigus & Pemphigoid Foundation
Goes to Austin: Patient Conference Recap
DR. AIMEE PAYNE'S NEW RESEARCH Closer to a cure?
FALL 2016 • ISSUE #86 PEMPHIGUS.ORG FALL 2016
10 14
FEATURES DEPARTMENTS 10 Engineering the Immune System Message from the Director 3 To Correct Its Own Flaws Marc Yale A Q&A WITH AIMEE PAYNE, MD, PHD Awareness Noelle DeLaney Greetings from the New 4 14 2016 Patient Conference IPPF Outreach Manager REPORT FROM AUSTIN, TEXAS Becky Strong Becky Strong Advocacy 18 The Walter Lever Rally for Medical Research 5 Memorial Lecture Award Sarah Gordon Tufts University School of Medicine The IPPF, American Academy of 6 Dermatology, and Me 5 Becky Strong Research Highlights Molecular Events at Play in PV and BP 8 Mirella Bucci, PhD
4 6
2 Quarterly | Fall 2016 www.pemphigus.org Quarterly The Journal of International Pemphigus & Pemphigoid Foundation Message from the ISSUE #86 | FALL 2016 The IPPF is a U.S. 501(c)(3) nonprofi t organization. EIN: 94-3207871 Director
BOARD OF DIRECTORS This issue of the Quarterly has great signifi cance Todd Kuh, Chairman Mert Erogul Mirella Bucci, PhD, Secretary William Gerstner to me and the team as we get to share the suc- Sonia Tramel, Treasurer David Sirois, DMD, PhD cess of the 19th Annual Patient Conference in David Baron Mindy Unger Austin, Texas. This year’s conference would not MEDICAL ADVISORY BOARD Sergei Grando, MD, PhD, DSci, UC Irvine, Irvine CA have been possible without the tireless eff ort of Noelle DeLaney, Patient Neil Korman, MC, PhD, Case Western Reserve University, Cleveland OH Services Manager. Our community owes her our gratitude. Although M. Peter Marinkovich, MD, Stanford University, Stanford CA Dedee F. Murrell, MD, University of New South Wales, Australia Noelle has left the foundation, she will continue to volunteer for the Animesh A. Sinha, MD, PhD, University of Buff alo, Buff alo NY IPPF in the future. The conference brought together many key individu- David A. Sirois, DMD, PhD, NYU College of Dentistry, New York NY Victoria Werth, MD, University of Pennsylvania, Philadelphia PA als of the pemphigus and pemphigoid community. Patients from across QUARTERLY STAFF the country, expert dermatologists, oral medicine specialists, disease Patrick Dunn, Editor-in-Chief, [email protected] researchers, IPPF board members, staff , and our pharmaceutical part- Toby Speed, Copyeditor ners all assembled to learn from one another and celebrate another CONTRIBUTING WRITERS Mirella Bucci, PhD successful year. I would like to extend a very special thank you to the Noelle DeLaney conference host, Dr. Terry Rees from Texas A&M School of Dentistry, Sarah Gordon Rebecca Strong, RN whose support was unwavering. Marc Yale As you can see by many of the articles in this edition, pemphigus and CONTENT REVIEW TEAM Vanessa Baron pemphigoid research is beginning to take front-and-center in our quest Sandra Gittlen for a cure. The IPPF is continually looking for ways to promote research Janet Segall opportunities, improve diagnostic delays, advocate for treatments, and COVER "Pennybacker Bridge: Austin, TX" by Patrick Dunn support each and every one of you. As you will discover in this edition, IPPF STAFF recent research by the Japanese group at Tohoku University, led by Dr. Marc Yale, Interim Executive Director Taku Fujimura and Dr. Setsuya Aiba, as well as work being done at the Kate E. Frantz, MPH, Awareness Program Manager Patrick Dunn, MFA, Communications Manager University of Pennsylvania by Dr. Aimee Payne and Dr. Michael Milone, Rebecca Strong, RN, Outreach Manager are just two examples of the possibilities for learning about disease trig- Monique Rivera, Administrative Assistant Mei Ling Moore, Peer Health Coach gers and treatments for our patients. Janet Segall, Peer Health Coach Jack Sherman, Peer Health Coach Pemphigus and pemphigoid awareness and advocacy opportunities con- Hannah Heinzig, BNS, Patient Educator Bryon Scott, Volunteer Awareness Ambassador Coordinator tinue to grow. Patient participation and physician recognition are taking Debra Fuentes, Cristo Rey Intern center-stage. Becky Strong is our new Outreach Manager, and she will Niko Pretelin, Cristo Rey Intern be working with all of our stakeholders to improve patient and physician INTERNATIONAL PEMPHIGUS & PEMPHIGOID FOUNDATION education, community engagement, and support services. In this issue, 1331 Garden Highway, Suite 100, Sacramento, CA 95833 toll free: 855-4PEMPHIGUS tel: 916-922-1298 you will learn how patients are getting involved in clinical trials, advocat- [email protected] | www.pemphigus.org ing with their congressional members, and submitting artwork to help POSTMASTER: Please send address changes to IPPF, 1331 Garden Highway #100, Sacramento, CA 95833, USA create awareness. Let us know how you want to get involved and become The Quarterly is published four times a year and provided free to empowered! donors as a thank you for their support. The material presented is not intended as medical advice or to promote one We are in an extraordinary time. Science and medicine are moving at an product or service over another. Readers should consult incredible pace. I am confi dent that the opportunity to fi nd a cure for their physicians before making changes to their health regimen. The contents of the Quarterly cannot be reproduced or pemphigus and pemphigoid could be within our reach. I continue to be copied without written permission from the IPPF. Inquiries should be directed to: IPPF, 1331 Garden Hwy #100, Sacramento CA 95833, inspired by all of you and your commitment to improving the quality of USA. The opinions of contributors are not necessarily life of all people aff ected by pemphigus and pemphigoid. those of the IPPF. We can reproduce articles and provide electronic copies of issues. If you would like to submit a story for Thanks for your support, consideration, please contact the Editor-in-Chief prior to submitting your story: [email protected] © 2016 International Pemphigus & Pemphigoid Foundation Printed in the USA by our friends at SUNDANCE PRESS, Tucson, AZ. www.sundancepress.com Marc Yale IPPF Executive Director [email protected] 4 www.PutItOnYourRadar.org Awareness H Quarterly BECKY STRONG Outreach Manager: Greetings fromtheNewIPPF for dentistsandmedicalprofessionals. take overcoordinatingexhibit boothsatconferences vise other patientspeakers andvolunteers. Iwillalso at universities and looking to recruit, train, and super outreach. I willbecoordinating patientpresentations dental on focuses Campaign Awareness the Currently, of reducingpatientsufferinganddiagnosticdelays. ness ofP/Pinthemedicalcommunitywithgoal groups, meetings,andpatienteducationcalls. and online, as well as helping to facilitate local support I willalsobecreating andrevising material for print resources. and information precise clear, with me tact allwhocon- toprovide contact. Itismyresponsibility question, comment, or concern, I am their first point of ing patients. If anybody touchedbyour diseaseshas a moting thebesttreatmentsforP/Ppatients. goals of education, early diagnosis, and pro- common the by united are they focuses, different have programs these While Campaign. Awareness Support andthe Patient alinkbetween tobe was created position This IPPF. the to as well as me, to one another. it’s amazinghowwesincerelycareabout nity pullstogetherandralliesforeachother; people. I am proud oftheway our commu- Foundation thatthisisan amazing group of the with contact first my from knew I trol. con- under got finally vulgaris pemphigus ested in doing for about five years, since my It sounds like a lot of work — and it is — but I amup work —anditisbut of like alot It sounds raising aware- The otherhalfofmyjobwillbespent support- spent be will time my of half result, a As The positionofOutreachManagerisnew - inter been Ihave something been elloIPPF has all!the Workingfor |Fall2016 - you need.Iamhereforyou. (916) 992-1298 x105. I willwork togetyoutheanswers [email protected] ful opportunitytodoso. P/P patients. And the IPPF has given me this wonder of lives the in difference a make to knowledge my use and others. ItismygoaltopassalongwhatI’velearned IPPF friends changedallofthat. I want todothatfor my But isolated. and felt scared Iwas I wasdiagnosed. one ofthelowestperiods ofmylife. I was youngwhen during encouragement and compassion, support, with me of youprovided many community. So IPPF the for the dental,medical,andnursingcommunities. of life for the members of our community, as well as in neously. Ipromisetoworktirelesslypromotequality - simulta communities both with work to qualified am I that feel I field, healthcare the in work past my and as aPV of mystatuspatient Because challenge! for the Please know you can contact me by email at byemail Please knowyoucancontact me weren’t it if I amtoday where be not I knowwould or by phone at phone orby www.pemphigus.org - Advocacy
Rally for Medical Research Sarah Gordon
n Thursday, September members were supportive of our experience, but also a powerful one. O22, I joined 350 advocates efforts to maintain NIH funding, I truly felt that our representatives on Capitol Hill for the Rally for especially Sen. Tester, who seemed were listening closely when I told Medical Research. Our main to have a vested interest in medi- them my story of being diagnosed goal was to encourage members cal research. In addition to our with, and treated for, pemphigus of Congress to continue robust, general request for NIH funding, I vulgaris. Meeting our lawmakers sustained, and predictable fund- stressed the importance of cutting in person and telling our stories ing for the National Institutes of edge research of rare diseases and makes all the diff erence! Health (NIH). Because I live in emphasized the signifi cance of the Washington, DC, a city without a Open Act, which incentivizes phar- Sarah Gordon is an art historian vote in Congress, I was assigned to maceutical companies to make and author. She teaches at Ameri- the group from Montana. treatments available off -label. can University and Photoworks at Along with a University of Of my three visits to Capitol Glen Echo, and she lectures at the Montana biologist and a can- Hill as a rare disease advocate, National Gallery of Art. Sarah was cer research advocate, I met with this is the fi rst time I met with the diagnosed with pemphigus vulgaris Sens. Jon Tester and Steve Daines, members themselves rather than in 2007. She lives in Washington, and Rep. Ryan Zinke. All three only their staff . It was a humbling DC, with her husband and two sons.
A Publication of the International Pemphigus & Pemphigoid Foundation Quarterly | Fall 2016 5 Advocacy
The IPPF, American Academy of Dermatology, and Me
Becky Strong
his past September, I had term “lobbying” was coined at the advocates to learn what their Tthe opportunity to travel to Willard by citizens tracking down organizations are doing, how part- Washington, DC, to represent President Grant while he smoked nerships can turn the tables, and the IPPF at the 2016 American cigars in the lobby. The League of tips to make our organizations more Academy of Dermatology (AAD) Nations was formed in this same eff ective. It was amazing to see just Legislative Conference. It was a hotel, and many famous people how cutting edge the IPPF is and great experience, and if you ever get have stayed there — including how many other organizations feel the chance — no matter how intim- George Clooney the same weekend we are leading the way in advocacy idated you feel — you should do it! I was there! and education. It really brought to From the moment I arrived, I The conference started with the forefront how talented our staff felt like history was about to be a Coalition of Skin Diseases and volunteers are and how much made. The conference was held at Development Day. It was a fantas- they have accomplished. the Willard InterContinental Hotel. tic opportunity to get to know other The AAD boot camp began on Urban legend proclaims that the rare — and not-so-rare — disease day two. Attendees were educated
6 Quarterly | Fall 2016 www.pemphigus.org on the issues dermatologists face and how dealed, and pleaded to make this coun- current and future legislation will aff ect try a better place for their children. I doctors and patients. We all know the knew patients like me could truly make a patient part of healthcare. We live it, and diff erence. it is our role. It was fascinating to get a My time on the Hill was scary and fun glimpse into the lives of doctors and the at the same time. It was hard being away impact legislation can have on their ability from my family and my job, but I was to treat patients. there for a cause much greater than me. It As patients, it is extremely important was greater than the IPPF. It was for each that we have accessible healthcare options and every patient who has had to suff er, and medications. We need to have compe- lacked health care, or couldn't aff ord nec- tition, even among generic companies, in essary medications. order to keep prices within the fi nancial There was a real sense of the power reach of patients. Speakers helped patients we have as patients. We are the constitu- and doctors see how these issues directly ents — the voters — who hold re-election affect them. This helped us prepare for power and have stories that tug on heart- meeting our senators and representatives. strings. We have the knowledge of what We were instructed about the impor- it is like to live with a rare disease. We tance of the people we would meet from are the reminder that bills and acts aren’t our senators’ and representatives’ offi ces. just words on a page; they aff ect real peo- While not everybody would meet with his ple. A “yea” or “nay” could have a lasting or her senator or representative, it was impact not only on our lives, but on the also critical to convince the aides and lives of everybody affected by pemphi- assistants of the importance of the issues. gus, pemphigoid, or other diseases. “Yea” These are the people who typically do the or “nay” could be the diff erence between research and help senators and represen- gaining access to lifesaving treatments tatives decide how they will vote. If you and not even being able to see a doctor. move the staff , it will get back to the boss. One patient’s mere presence and story can The conference speakers also pointed have a profound eff ect on how a senator or out how important follow-up would be, as representative will vote. it’s not enough to simply state your case. While it will be a while before I fi nd out It is every bit as important to stay on their how effective we were that day, we lob- radars. My personal follow-up technique bied. We made our voices heard with the was to ask senators and representatives conviction of seasoned professionals. We to take a photo with me while wearing the the people came together to stand for the IPPF’s orange #healourskin sunglasses. issues that aff ect us most. We stated our Then, a few days later, I sent the picture case as to why we require our senators and and reiterated the importance of their representatives to stand with us. Each and support to the acts and bills we discussed. every one of us there made a difference Capitol Hill Day was the best day ever. that day. We spoke for those who cannot Walking through the diff erent offi ce build- always speak for themselves. It was pow- ings on the Hill quickly brought to mind erful. It was fun. It was American. the fact people have walked those halls for 200 years. They shaped this country On this page (from top): Becky Strong to what is today. with Rep. Sander Levin (MI), Sen. Debbie During meetings in those same offi ces, Stabenow (MI), Rep. John Moolenaar great men and women have wheeled, (MI), and Sen. Gary Peters (MI).
Journal of the International Pemphigus & Pemphigoid Foundation Quarterly | Fall 2016 7 Molecular Events at Play in PV and BP
Mirella Bucci, PhD
research group in Japan has been studying the to be increased in PV and BP. In their recently pub- Amolecular basis of autoimmune mucocutaneous lished work in the journal Experimental Dermatology blistering diseases and, in a recent study, they’ve iden- (http://onlinelibrary.wiley.com/doi/10.1111/ tified a link between a protein, POSTN, that has already exd.13157/abstract) the researchers found by immuno- been implicated in inflammatory skin diseases, and a histochemical staining that dense deposits of POSTN particular immune cell type that is elevated in pemphi- were formed in the inflamed tissue from PV and BP gus vulgaris (PV) and bullous pemphigoid (BP). Their patients, specifically in the superficial dermis, where results also serve to help distinguish PV and BP at a these macrophages are known to reside. Following the molecular level. cascade of signals known to take place downstream of The immune system is made up of several types of POSTN, they narrowed in on the chemokine CXCL5, specialized cells that are involved in a cascade of events since this has been implicated in other autoimmune Research Highlights that lead to execution of foreign cells, such as bacte- diseases including multiple sclerosis and rheumatoid ria, or that promote an inflammatory response, such arthritis. Not only were they able to show that the as during an injury. During inflammation — including disease-linked CD163+ macrophages were activated inflammation that occurs at pemphigus and pemphi- in disease, they also found that while CXCL5 was sig- goid lesions — one type of immune cell, macrophages, nificantly elevated in the blood of PV patients, it was recruit other immune cells, T cells, which ultimately unchanged in BP compared to non-diseased patients. lead to lesion formation and inflammation. These cells communicate with each other through immune-mod- ulating proteins called cytokines, chemokines, and matrix metalloproteinases (MMPs) that are secreted by macrophages and sensed by T cells. It has been shown that a specific subset of macrophages, those expressing a protein called CD163, are elevated in PV and BP. Yet, these two diseases have different sets of T cells, suggesting that communication between mac- Immunohistochemial staining rophages and T cells differ at the level of production of of skin tissue from a PV patient the immune-modulating proteins. shows deposition of POSTN (red) The Japanese group at Tohoku University, led by Dr. at a lesion. Photo: Taku Fujimura Taku Fujimura and Dr. Setsuya Aiba and driven by a desire to understand PV and BP at a molecular level, Since POSTN has been shown previously to stimu- predicted that POSTN, which is already known to be late CD163+ macrophages to increase the levels of the involved in maturation of macrophage cells, might be at MMP, MMP12, the authors looked at this protein as play in these diseases and that it might function at the well and found differences again in PV compared to level of a specific class of macrophage cell, the CD163- BP. In PV, they saw MMP12 deposits in the upper layer positive (CD163+) macrophages, which are known of epidermis and superficial dermis in PV lesions but
8 Quarterly | Fall 2016 www.pemphigus.org only in the superficial dermis in BP lesions. Finally, the These results suggest that POSTN stimulation of researchers identified several cytokines that are known CD163+ macrophages could trigger PV via secretion of to be correlated to pathogenesis of autoimmune bul- CXCL5 as well as IL-36γ, which is known to interact lous diseases and looked for the induction of these by with the very cells, keratinocytes, whose adhesion to POSTN and for their production in lesion skin in the one another is corrupted in PV skin. two diseases. From this analysis, they found the cyto- kine IL-36γ in epidermal keratinocytes and infiltrating Mirella Bucci, PhD, is Secretary of the IPPF Board of leukocytes (another type of immune cell) in PV lesions Directors and a scientific journal editor living in San and in epidermal keratinocytes, but only weakly in Mateo, California. She is a regular contributor to the infiltrating leukocytes in BP. Quarterly in the Research Highlights column.
The EveryLife Foundation for Rare Diseases is pleased to announce the 8th Annual Rare Artist Contest, which celebrates the unique talents of the rare disease community. Two award recipients will be chosen from each category. One will be decided by popular vote on Facebook. The other will be chosen by a panel of rare disease community leaders Pieces selected as award recipients or for special artistic merit awards will be displayed at the Rare Artist Reception, held in conjunction with RDLA’s Rare Disease Week on Capitol Hill. Artists with works chosen for this reception will be eligible for travel stipends through The EveryLife Foundation for Rare Diseases Rare Giving program, to provide the artists the opportunity to see their work displayed on Capitol Hill. CATEGORIES Children (4-11): $100 gift card Teens (12-18): $250 gift card Adults (18+): $500 gift card Adults - Photography/Digital Art: $500 gift card
For more info, visit www.rareartist.org/2016-art-contest
Journal of the International Pemphigus & Pemphigoid Foundation Quarterly | Fall 2016 9 Engineering the Immune System to Correct Its Own Flaws A Q&A WITH AIMEE PAYNE, MD, PHD
n a study with potentially major implications for the future treatment of Iautoimmunity and related conditions, scientists from the Perelman School of Medicine at the University of Pennsylvania have found a way to remove the subset of antibody-making cells that cause an autoimmune disease, without harming the rest of the immune system. The autoimmune disease the team studied is called pemphigus vulgaris (PV), a condition in which a patient’s own immune cells attack a protein called desmoglein-3 (Dsg3) that normally adheres skin cells. Current therapies for autoimmune disease, such as prednisone and ritux- imab, suppress large parts of the immune system, leaving patients vulnerable to potentially fatal opportunistic infections and cancers.
10 Quarterly | Fall 2016 www.pemphigus.org The Penn researchers demonstrated their new which studies CAR T cell technology, in the hope of technique by successfully treating an otherwise fatal finding a powerful new way to treat these ailments. autoimmune disease in a mouse model, without appar- “We thought we could adapt this technology that’s ent off-target effects, which could harm healthy tissue. really good at killing all B cells in the body to target The results are published in an online First Release specifically the B cells that make antibodies that cause paper in Science. “This is a powerful strategy for tar- autoimmune disease,” said Milone. “Targeting just the geting just autoimmune cells and sparing the good cells that cause autoimmunity has been the ultimate immune cells that protect from infection,” said the goal for therapy in this field,” noted Payne. A more study’s co-senior author Aimee S. Payne, MD, PhD, the disease-specific receptor In the new study, for which Albert M. Kligman Associate Professor of Dermatology. Ellebrecht was first author, the team took aim at pem- Payne and her co-senior author Michael C. Milone, phigus vulgaris. This clinically serious condition occurs MD, PhD, an assistant professor of Pathology and when a patient’s antibodies attack molecules that nor- Laboratory Medicine, adapted the technique from the mally keep skin cells together. When left untreated, PV promising anti-cancer strategy by which T cells are leads to extensive skin blistering and is almost always engineered to destroy malignant cells in certain leu- fatal, but in recent decades the condition has been kemias and lymphomas. “Our study effectively opens treatable with broadly immunosuppressive drugs such up the application of this anti-cancer technology to the as prednisone, myco- treatment of a much wider range of diseases, including phenolate mofetil, "…the word “cure” autoimmunity and transplant rejection,” Milone said. and rituximab. The key element in the new strategy is based on an To treat PV with- is potentially within artificial target-recognizing receptor, called a chimeric out causing broad our reach with this antigen receptor, or CAR, which can be engineered into immunosuppres- patients’ T cells. In human trials, researchers remove sion, the Penn team technology." some of patients’ T cells through a process similar designed an artificial to dialysis and then engineer them in a laboratory to CAR-type receptor that would direct patients’ T cells add the gene for the CAR so that the new receptor is to attack only the B cells producing harmful anti-Dsg3 expressed in the T cells. The new cells are then mul- antibodies. The team developed a “chimeric autoanti- tiplied in the lab before re-infusing them into the body receptor,” or CAAR, that displays fragments of patient. The T cells use their CAR receptors to bind to the autoantigen Dsg3 — the same fragments to which molecules on target cells, and the act of binding trig- PV-causing antibodies and their B cells typically bind, gers an internal signal that strongly activates the T as Payne’s laboratory and others have shown in prior cells — so that they swiftly destroy their targets. The studies. The artificial receptor acts as a lure for the B basic CAR T cell concept was first described in the late cells that target Dsg3, bringing them into fatal contact 1980s, principally as an anti-cancer strategy, but tech- with the therapeutic T cells. Testing many variants, nical challenges delayed its translation into successful the team eventually found an artificial receptor design therapies. that worked well in cell culture, enabling host T cells Since 2011, though, experimental CAR T cell treat- to efficiently destroy cells producing antibodies to des- ments for B cell leukemias and lymphomas — cancers moglein, including those derived from PV patients. in which patients’ healthy B cells turn cancerous — have The engineered T cells also performed successfully in a been successful in some patients for whom all standard mouse model of PV, killing desmoglein-specific B cells therapies had failed. B cells, which produce antibod- and preventing blistering and other manifestations of ies, can also cause autoimmunity. Payne researches autoimmunity in the animals. “We were able to show autoimmunity, and a few years ago, a postdoctoral that the treatment killed all the Dsg3-specific B cells, researcher in her laboratory, Christoph T. Ellebrecht, a proof of concept that this approach works,” Payne MD, took an interest in CAR T cell technology as a said. T cell therapies can be complicated by many fac- potential weapon against B cell-related autoimmune tors. But in these experiments, the Penn scientists’ diseases. Soon Payne’s lab teamed up with Milone’s, engineered cells maintained their potency despite
Journal of the International Pemphigus & Pemphigoid Foundation Quarterly | Fall 2016 11 the presence of anti-Dsg3 antibodies that might have fusing them to pathogen-killing T cells. By tweaking swarmed their artificial receptors. In addition, there this technique, researchers can create an arsenal of T were no signs that the engineered T cells caused side cells that target a specific pathogen – or in the case of effects by hitting the wrong cellular targets in the mice. autoimmune diseases, the abnormal B cells. Pemphigus The team now plans to test their treatment in dogs, vulgaris (PV) is a life-threatening autoimmune disease which also can develop PV and often die from the dis- that results in blistered skin. Here, the team harvested ease. “If we can use this technology to cure PV safely in the key protein, Dsg3, that disease-causing B cells dogs, it would be a breakthrough for veterinary medi- recognize, and fused it to signaling proteins that acti- cine, and would hopefully pave the way for trials of this vate T cells. When the researchers infused mice with therapy in human pemphigus patients,” Payne said. the engineered T cells, their levels of Dsg3-targeting Also on the horizon for the Penn scientists are appli- B cells decreased, as did the occurrence of blisters. cations of CAAR T cell technology for other types of Furthermore, these engineered T cells can divide and autoimmunity. The immune rejection that complicates proliferate, the researchers show, suggesting that CAR organ transplants, and normally requires long-term techniques to treat PV, and perhaps other autoimmune immunosuppressive drug therapy, may also be treat- diseases, could have long-lasting effects. able with CAAR T cell technology. “If you can identify a specific marker of a B cell that you want to target, What does this mean for our community? then in principle this strategy can work,” Payne said. In Noelle DeLaney asked Dr. Payne. addition to Payne, Milone and Ellebrecht, co-authors Noelle DeLaney (ND): Can you speculate about how of the study include Vijay G. Bhoj, Arben Nace, Eun this treatment might be translated to clinical practice? Jung Choi, Xuming Mao, Michael Jeffrey Cho, John T. Seykora and George Cotsarelis, all of Penn; Giovanni Dr. Aimee Payne (AP): CAR-T cells have already Di Zenzo of the Istituto Dermopatico dell’Immacolata been used in humans to treat cancer. At this point in in Rome; and Antonio Lanzavecchia of the Institute for time, we have generated just about the same amount of Research in Biomedicine in Bellinzona, Switzerland. preclinical data as our cancer colleagues showed prior Researchers have engineered T cells to target and to starting clinical trials in humans, but pemphigus is kill a malfunctioning component of the immune sys- not as quickly fatal as the cancers were in the initial tem responsible for autoimmune disease, while sparing patients they treated. Thus, we want to set a “higher healthy immune cells that still protect the body. The bar” of evidence that these CAAR-T cells will work in work brings scientists closer to targeting only the dis- pemphigus. So we are taking a two-pronged approach: ease-causing cells in autoimmune diseases, which isn’t we are initiating discussions on how we would design possible now. Some autoimmune diseases occur when and gain approval for a first-in-human trial for CAAR-T a subset of B cells, which respond to specific signatures cells, and at the same time we are seeking to open clini- of pathogens, incorrectly see a person’s own tissue as cal trials for dogs with pemphigus. Dogs are one of the foreign, prompting the rest of the immune system to only animals other than humans that spontaneously attack. Currently, strategies to treat autoimmune dis- develop pemphigus. If we can show that we can safely eases involve wide-sweeping immunosuppression, treat and potentially cure dogs with pemphigus, we which can leave a patient more susceptible to infection; think that will convince both doctors and patients to what’s more, patients often experience relapse follow- begin enrolling for human clinical trials of CAAR-T ing such treatments. Now, initial results in mice by therapy. Christoph Ellebrecht et al. show that a more targeted ND: Is there a role for Pharma? If not, how will clinical approach may be viable for treating autoimmune dis- trials be funded? ease. Inspired by a technique that has recently shown success for treating leukemia, the researchers explored AP: Yes. The right partnerships will be essential. how chimeric antigen receptors (CARs) may be used to Pharmaceutical companies, universities, the National target rogue B cells. CAR techniques involve harvesting Institutes of Health (NIH), and philanthropic donors the antibodies that trigger an immune response and have funded the CAR-T cell work in cancer. We need
12 Quarterly | Fall 2016 www.pemphigus.org to make sure we have adequate resources to support disease and potential treatments for these diseases. Our the lab-based scientists, clinical treatment teams, and community is in danger of losing outstanding research overall research infrastructure to safely and effectively programs, and once that infrastructure is gone, there move forward this technology to human clinical trials. won’t be the intellectual capital remaining to make sure that future generations of doctors and researchers ND: How is it that this could qualify as an actual cure? continue to focus on these devastating diseases. Please AP: The unique feature of CAAR-T cells is that they keep up all the great work you are doing at the IPPF are a “living therapy.” Unlike an antibody-based ther- in regard to advocacy and meetings to bring together apy, in which a defined dose is infused, CAAR-T cells doctors, researchers, and patients to talk about their can expand over a thousandfold in vivo when they see disease and what the future may hold. their target (they can spawn new soldiers to fight off the enemy, if you will.) Additionally, we know from prior More about Dr. Payne studies that they can also make memory T cells that Aimee Payne, MD, PhD, is the Albert M. Kligman can persist for decades. So you only infuse the CAAR-T Associate Professor of Dermatology at the University cells once, and they will kill all pemphigus B cells, of Pennsylvania. Her career interest has been in pem- then go dormant. If a pemphigus B cell should recur phigus: diagnosing and treating patients with this at any point in the future, the memory CAAR-T cells potentially fatal autoimmune disease, and performing can expand again and kill them. This exciting aspect research to better understand disease, with the goal is why CAR-T cells were named by both the director of improving therapy. Dr. Payne received her BS in of the NIH and Vice President Joe Biden as part of the Biology from Stanford University and her MD/PhD “moonshot” to cure cancer — the word “cure” is poten- from Washington University School of Medicine, fol- tially within our reach with this technology. lowed by residency and postdoctoral fellowship training in dermatology at the University of Pennsylvania. Her ND: Do you have any information for patients wanting laboratory has cloned B cell repertoires from pemphi- to participate in future trials? gus patients to better understand why disease occurs, AP: Stay tuned! We are still some amount of time away research that has revealed common features of the from human trials. immune response among patients. Her laboratory has also focused on patient-oriented research to improve ND: Are there implications for other diseases or types pemphigus therapy, which has led to a better under- of diseases/disorders this treatment could be used for standing of how rituximab works in pemphigus, as well (autoimmune and other)? as on the development of novel targeted therapies. AP: Yes, this therapy could theoretically be used for Dr. Payne’s work in the field has been recognized any antibody-mediated disease, including other auto- with the American Academy of Dermatology Young immune blistering diseases like bullous pemphigoid, Investigator Award, the Charles and Daneen Stiefel epidermolysis bullosa acquisita, and even non-skin Award in Autoimmune Diseases, the Sanofi Innovation autoimmune diseases such as myasthenia gravis and Award, and election to the American Society for Clinical many others. Investigation. Dr. Payne is also active in mentoring the next generation of physician-scientists through ND: What do you want pemphigus and pemphigoid teaching medical students, graduate students, and der- patients to take away from this? matology residents. She serves as Associate Director of AP: We are optimistic that research will lead to better the Medical Scientist Training Program at Penn and therapies and options for pemphigus and pemphigoid faculty advisor for the Association of Women Student patients, but it’s by no means easy! Research support MD-PhDs (AWSM). from the NIH and other sources has been dwindling over the last several years, and due to the rarity of pem- Now a volunteer, Noelle DeLaney was the IPPF's phigus and pemphigoid, it has become increasingly Patient Services Manager for two-and-a-half years. difficult to advocate for research into mechanisms of She lives in Dixon, CA with her husband.
Journal of the International Pemphigus & Pemphigoid Foundation Quarterly | Fall 2016 13 2016 Annual Patient Conference
REPORT FROM AUSTIN TX
Becky Strong
ow! The 2016 Patient Conference has already to obtain a diagnosis. Together, we presented the whole Wcome and gone. It was an amazing experience picture of diagnosing, treating, and living with an auto- for attendees and presenters alike. This year’s event immune blistering disease. focused on the importance of peer support and expert Thursday night’s Cocktail Hour, Awards Dinner, and research, and there was a special emphasis on oral Casino Night were all held at Eighteenth Over Austin care. The conference was full of learning, laughs, and — a beautiful venue with 180 degree views of the city the formation of life-changing bonds. skyline. Aimee Payne, MD, PhD, Associate Director The Hilton Garden Inn Downtown Austin is located of the Medical Scientist Training Program at the close to some of the best food and entertainment in University of Pennsylvania, gave the keynote speech. the city. Austin’s 6th Street has been a famous enter- This included an exciting glimpse into the poten- tainment hub since the 1970s. It’s home to South By tial breakthroughs of her current research. The IPPF Southwest — Austin’s famous music and film festival — Awards Dinner recognized many people who have as well as the Pecan Street Festival, which attendees got worked hard, both in front of and behind the scenes, to catch a bit of after the conference. The street itself is at the Foundation. closed to vehicle traffic on Friday and Saturday nights At Casino Night, patients, doctors, and research- and becomes a pedestrian paradise filled with lights, ers alike tried their hand at games of skill and luck to music, and bustling people. Thursday, 9/22 Terry Rees, DDS, MSD, Director of the Stomatology Center at Texas A&M University College of Dentistry, and I started the conference by giving a joint continu- ing education presentation to local dentists and patient attendees on pemphigus and pemphigoid (P/P) and the reason why early diagnosis is so important. Dr. Rees covered the academic content of managing patient care, while I gave a personal testimony of my journey
14 Quarterly | Fall 2016 www.pemphigus.org see who could gather the most chips by the end of the night. Marc Yale, IPPF Executive Director, served as MC, calling out the numbers of winning raffle tickets. Prizes included a Samsung Galaxy Tablet, FitBits®, Sonicare™ electric toothbrushes, Waterpik® flossers, and more! Friday 9/23 Friday began with opening remarks from Dr. Rees and Marc Yale. Todd Kuh, IPPF Board Chairman, introduced the Board of Directors and staff. member of the IPPF Awareness Committee and Dental Sergei Grando, MD, PhD, and a leading P/P expert Advisory Council; and Michaell Huber, DDS, professor from UC Irvine, gave a lecture on IVIG. Next, Victoria at the University of Texas HSC San Antonio. This panel Werth, MD, Professor of Dermatology and Medicine gave the patients a chance to ask questions that would at the University of Pennsylvania, and Member of the help them improve their overall oral health. Topics IPPF’s Medical Advisory Board, spoke of the treat- covered included mouth rinses, brushing techniques, ments that are commonly used to treat our diseases. and the best kinds of toothbrushes for P/P patients. She covered why steroids and immunosuppressants After lunch, participants had the opportunity to work to treat P/P, as well as how they work. Dr. Werth choose from different breakout sessions. also covered many of the side effects and complications The first group of sessions included topics as diverse that come with using such strong medications. as “below the belt” with A. Razzaque Ahmed, MD; clinical Kim Yancey, MD, Professor and Chair of the trials with Diana Chen, MD, MBA, FAAD; disease-specific Department of Dermatology at the University of Texas patient reported outcomes with Badri Rengarajan, MD; Southwestern Medical Center in Dallas, covered the use and ophthalmology with Dennis Kay, MD. of topical treatments in the care of patients with ocu- The next group included a sessions on insurance from lar, nasal, and oral disease involvement. He stressed BioFusion’s Dinesh Patel, IVIG from Dr. Ahmed, oral the importance of regular checkups with eye doctors, care from Dr. Rees and Dr. Burkhart, and Rituximab dentists, and ENT doctors, as well as the role of derma- and next generation therapies from Dr. Payne. tologists in managing lesions. The final breakout sessions featured Dr. Payne’s These lectures were followed by a Q&A session lecture, “Future Targeted Therapy of Pemphigus,” as where patients and caregivers were given the chance to well as ”Mindfulness Based & Positive Psychology with ask questions that were not answered in the lectures. P/P” by Terry Wolinsky-McDonald, PhD; Dr. Ahmed’s Sessions like these give patients power over their dis- “Pemphigoid Q&A”; and Dr. Sinha’s “Pemphigus Q&A.” eases because they give them a chance to have an active The day ended with Dr. Kay, Dr. Ahmed, Dr. Sinha, dialog with experts. and Dr. Payne sitting for a Q&A session, followed by After a short break, Animesh Sinha, MD, PhD, cocktails and cupcakes. Many attendees then made professor and dermatologist at SUNY Buffalo, gave their way out to explore the best that downtown Austin a lecture on genetics. He explained certain genetic had to offer. characteristics that most P/P patients share with one another and how blood samples collected at the IPPF’s Saturday, 9/24 Patient Conferences over the years have helped him in Saturday was a day for patients by patients. The his research. morning started with breakfast and another oppor- Dr. Rees participated in an oral care panel with tunity to bond with fellow patients. Camaraderie is Nancy Burkhart, RDH, EdD, adjunct associate profes- so important with P/P. Our diseases can be isolating, sor at Texas A&M College of Dentistry and member of and it was awesome to meet others who have walked the IPPF Dental Advisory Council; Paul Edwards, MSc, the same path, many of whom are well on their way to DDS, FRCD(C), professor at Indiana University and remission.
Journal of the International Pemphigus & Pemphigoid Foundation Quarterly | Fall 2016 15 Photos by Jack Sherman and Patrick Dunn. Mei Ling Moore started the morning sessions with a American Academy of Dermatology. Marc broke down guided meditation and de-stressing presentation, help- barriers and empowered everybody in the room. He ing us all to be open to the day ahead. made us aware that we, as patients, have the power to Next, Valhalla Holeman led us through the emo- change laws in this country. It was truly inspiring. tional story of her son Laten’s struggle with pemphigus Todd Kuh then gave a lecture on his “Chasing Down foliaceous. There were not many dry eyes during the Pemphigus” fundraiser. Todd shared the story of how presentation. Laten’s quiet strength — along with the he felt after being diagnosed with PV and how a single support of his sister and brother, Myles and Coale, sit- conversation inspired him to regain the active lifestyle ting next to him — was truly inspirational. he led before his diagnosis. IPPF Peer Health Coaches Mei Ling Moore and Janet After Todd, it was my turn to present “The Power Segall, IPPF Board Member Dave Baron, and I led a of You.” There was a time when I felt I had lost my patient-to-patient panel. There were so many good voice to PV, the treatments, and the side-eff ects of the questions and comments, and it really seemed to bond medication. But somebody told me that patients are our community more tightly together once again. the true experts because we live with the disease. That Roy Vongtama, MD, reinforced the mind-body con- inspired me to fi nd my voice again, and my presenta- nection in his lecture. He explained how we might not tion focused on the ways we can all be advocates and have control over the stressors in our lives, but we do share our expertise. have control over how they affect us. Dr. Vongtama After the fi nal presentations, Dr. Rees and Marc gave then showed how posture, breathing, and meditation their closing remarks and hopes for all P/P patients. aff ect overall health. Everybody was touched. After two days of intensive IPPF Awareness Ambassador Coordinator and inspiring lectures, attendees left feeling united. It Bryon Scott discussed the Awareness Ambassador felt like we mattered. Doctors cared about the plights program and simple ways we can all spread aware- of patients like us. Patients felt like they had renewed ness in our networks and with our own dentist. hope. Some reinforced old friendships from past con- Anyone interested in getting involved should email ferences, while others forged new relationships. I’m [email protected]. looking forward to what the IPPF has to off er in 2017! Marc Yale then spoke of the work he is doing to advo- cate at the state and federal level. Marc is a true gem Becky Strong is a PV patient and the IPPF Outreach to the foundation. He has lobbied for Rare Disease Manager. She was diagnosed in 2010, but is currently Day in California and has stormed Capitol Hill with in remission. She lives in Michigan with her husband the National Organization on Rare Disorders and the Tim and her young family.
16 Quarterly | Fall 2016 www.pemphigus.org Photos by Jack Sherman and Patrick Dunn. IPPF Awards PHYSICIAN OF THE YEAR Aimee Payne, MD, PhD DENTAL PROFESSIONAL OF THE YEAR Paul Edwards, MSc, DDS, FRCD(C) STAR AWARD EDUCATION Rebecca Strong Hannah Heinzig STAR AWARD OUTREACH Rudy Soto STAR AWARD SUPPORT Mei Ling Moore Mary Lee Jackson Rudy Soto Nancy Corinella Ellen Levine Sam Iwamoto Esther Nelson BRIGHT STAR AWARD Noelle DeLaney FOUNDERS AWARD Marc Yale
Quarterly | Fall 2016 17 The Walter Lever Memorial Lecture Award Department of Dermatology, Tufts University School of Medicine Boston, MA
Service at the Tufts University Medical School and subsequently the Chairman of the Department of Dermatology. He developed a strong research program that trained many young dermatolo- gists who eventually became chairmen of many dermatology departments. In 1983, Dr. Lever returned to Germany. He died on his birthday in 1992. He wrote many books, but the one that was most widely read and trans- lated into 16 languages was Lever’s Textbook of Histopathology. Dr. Lever was the first person to separate pem- phigoid from pemphigus, thus creating a new blistering disease. Hence, from a clinical perspective and a scientific view- point Walter Lever laid the foundation stone for what subsequently emerged as a subspecialty of dermatology, namely immunodermatology, which is mainly alter F. Lever, MD was one of the prominent autoimmune blistering diseases. Wdermatologists in the United States, during his To commemorate this enormous milestone in the professional life and thereafter. In the course of his history of modern dermatology, and as a token of career he made landmark contributions. His discover- respect for one of the most illustrious Chairmen of the ies affected patients with blistering diseases then and Department of Dermatology, the Memorial Lecture even today. His legacy will last forever. Award was created. It is given once in 25 years for the Dr. Lever was born in Germany in 1909. He initially following reason. It takes one or more decades to prove studied in Heidelberg and got his medical degree from that any major advancement can be readily reproduced the University of Leipzig. Many young professionals and the benefits from it are verified by physicians were immigrating to the US because of political ten- across the globe. Dr. Ahmed was cited for discov- sions in Europe. Dr. Lever was one of them. In 1936 ery of antibodies to beta 4 and alpha 6 integrins in he joined the Massachusetts General Hospital to do a mucous membrane pemphigoid and for identifying the residency in dermatology. He stayed there for 20 years ability of the combination of intravenous immunoglob- working with a prominent focus in dermatopathol- ulin and rituximab in producing long-term, sustained ogy. In 1959, he became the Chief of the Dermatology remissions in autoimmune blistering diseases.
18 Quarterly | Fall 2016 www.pemphigus.org Bullous Pemphigoid (BP)
About Bullous Pemphigoid Circulating autoantibodies bind Bullous Pemphigoid (BP) is an acquired autoimmune skin blistering disease. It is a very rare to antigen BP 180 in the skin disease that usually occurs in the elderly, but is actually the most common of the autoimmune A high density of autoantibodies induce skin blistering diseases. BP affects a lower layer of the skin, between the epidermis and complement binding and production of cytokines and chemokines in mast cells, the dermis, creating blisters that do not break easily. Lesions present predominantly on including eotaxin-1 the abdomen, groin, back, arms and legs, but occasional patients may have involvement of the mucous membranes. The first symptoms are usually patches of itchy skin followed by blisters in as early as one week. The blisters may itch and be painful.
Bullous Pemphigoid Facts • Bullous Pemphigoid generally responds to systemic corticosteroids (alone or combined Eosinophil-derived proteases Eotaxin-1 binds to CCR3, the with other oral agents), with most patients improving on prednisone at high dosages promote blister formation and main chemokine receptor but there is no consensus on optimal dosing. induction of concomitant expressed on eosinophils to inammation induce eosinophil migration • High-potency topical corticosteroids are also commonly used for the management of BP, and may be used as monotherapy for patients with mild disease.
• ~70% of patients treated with systemic corticosteroids su er from toxicities and major short and long-term side e ects including but not limited to diabetes, glaucoma, peptic ulcers, skin atrophy and psychosis. Migration of eosinophils • Because of this toxicity pro le of systemic corticosteroids, there is tremendous need for into the skin leads to secretion new and better therapeutic options. of large amounts of eosinophil- derived proteases For more information, please visit www.Immunepharma.com or www.pemphigus.org
Source: Neil J. Korman, M.D., Ph.D., Department of Dermatology at Case Western Reserve University and University Hospitals Case Medical Center.
Immune Pharmaceuticals, Inc. | www.immunepharma.com
Immune Pharmaceuticals is conducting a Phase clinical trial (BP- ) to study the Clinical Trial US Sites effects of bertilimumab in US Site Investigator Location patients with newly diagnosed Case Western Joshua Arbesman, MD Cleveland, OH moderate to extensive BP. Duke University Russell Hall, MD Durham, NC
Mount Sinai Annette Czernik, MD New York, NY • Bertilimumab is an experimental therapy targeting eotaxin-1, a pro-inflammatory protein which is believed to play a role in BP. University at Buffalo Animesh Sinha, MD Buffalo, NY • Eotaxin-1 is found elevated in the serum and in the blister fluid. Eotaxin-1 attracts specific cells from the University of Iowa Janet Fairley, MD Iowa City, IA Bullous Pemphigoid Facts blood stream into the skin, including the eosinophils. • Bullous Pemphigoid generally responds to systemic • ~70% of patients treated with systemic corticosteroids • The study treatment consists of three infusions corticosteroids (alone or combined with other oral suffer from toxicities and major short and long-term of bertilimumab (the study drug) along with oral University of Utah Kristina Callis Duffin, MD Salt Lake City, UT agents), with most patients improving on prednisone side effects including but not limited to diabetes, corticosteroids that will be tapered according at high dosages but there is no consensus on glaucoma, peptic ulcers, skin atrophy and psychosis. to the clinical response as assessed by the optimal dosing. study physicians. Two Additional Sites in Israel • Because of this toxicity profile of systemic • High-potency topical corticosteroids are also corticosteroids, there is tremendous need for new For more information about the trial visit commonly used for the management of BP, and and better therapeutic options. www.clinicaltrials.gov and search for NCT02226146. may be used as monotherapy for patients with For more information on Immune visit mild disease. www.immunepharma.com
For more information on IPPF visit www.pemphigus.org International Pemphigus & Pemphigoid Foundation Nonprofi t Org. 1331 Garden Highway #100 • Sacramento, CA 95833 US Postage 855-4PEMPHIGUS • 916-922-1298 • Fax: 916-922-1458 PAID [email protected] | www.pemphigus.org TUCSON, AZ Permit No. 271 Is this your last issue? CHECK THE EXP DATE IN THE ADDRESS LABEL RETURN SERVICE REQUESTED
THANKS TO OUR 2016 PATIENT CONFERENCE SPONSORS:
IMMUNE Pharmaceuticals
A. RAZZAQUE AHMED, MD, DSc
Quarterly Journal of the International Pemphigus & Pemphigoid Foundation