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FSH Society Annual International Research Consortium
The workshop includes platform and poster presentations. Attendees are requested to submit abstracts in advance. Abstracts are scored on priority and allocated to platform or poster presentations. An abstract booklet is made available at the meeting and is sent to the attendees a week in advance. The 2012 International Research Consortium & Research Planning Meetings to be Held in San Francisco The 2012 FSH Society FSHD International Research Consortium workshop will be held on Tuesday, November 6, 2012, as a satellite/ancillary meeting prior to the opening of the American Society for Human Genetics (ASHG) in San Francisco, California. We are delighted to have the meeting in the context of ASHG. Tuesday, November 6, is the only whole day made available to hold a meeting contiguous to ASHG. Approximately 80 scientists, patients, advocates, biotech and pharmaceutical companies, and clinicians from throughout the world gathered at a satellite meeting of the Annual Meeting of the American Society of Human Genetics in San Francisco on November 6, 2012, to share the latest progress in facioscapulohumeral muscular dystrophy (FSHD) research at the 2012 FSHD International Research Consortium and Research Planning meetings . The goal of this meeting was to explore and verify the complex genetic mechanism and various features of FSHD, to allow us to begin considerations to move into the development of potential treatments for FSHD. Dr. Silvère van der Maarel (Leiden University Medical Center, Leiden, the Netherlands and co-PI of the Fields Center for FSHD and Neuromuscular Research) was the European research co-Chair while Dr. Rabi Tawil (University of Rochester Medical Center, Rochester, NY and PI of the Fields Center for FSHD and Neuromuscular Research) was the clinical co-Chair. Daniel Perez, President & CEO of the FSH Society, Watertown, Massachusetts served as the organizational Chair. Other research directors attending the meeting were Drs. Sanjay Bidichandani and Paul Muhlrad of Muscular Dystrophy Association United States (MDAUSA), Tucson, Arizona, Mr. Bill Moss and Dr. Alan Watts of FSHD Global Research of Australia, Dr. Julie Dumonceaux represented , Association Française Contre les Myopathies (AFM), Paris, France, and Dr. Dan Miller of Friends of FSH Research, Seattle, Washington. All volunteer agencies working on FSHD were invited by the organizers and encouraged to attend. All program directors of muscular dystrophy at NIH were invited; Melisa Parisi of NICHD and John Porter NINDS had intended to attend but had last minute personal emergencies. Sponsors for the research workshop included: AFM, FSH Society, FSHD Global Research Foundation, NIH Eunice Kennedy Shriver NICHD Boston Biomedical Research Institute Sen. Wellstone MDCRC, MDA, and Genzyme. Together and under chairmanship of Dr. Louis Kunkel we reviewed last year’s research priorities and at the end of the day reprioritize them in light of recent developments. Sufficient time was allowed after each of four platform sessions each moderated by a distinguished scientist whose role was to provide a stimulating overview of the topic and facilitate discussion. The meeting was a working meeting with experts, developing future plans in the context of what we know now. It was a very successful workshop with a positive, constructive and collaborative atmosphere where new and unpublished findings were communicated to the audience, and with excellent interaction between all research groups and funding agencies. Also, excellent to see most all FSHD organizations working extremely well together side by side in the common front to solve and treat FSHD. Efforts towards a comprehensive global support scheme were further discussed two days later at the November 8 “Champions meeting” where virtually all FSHD organizations gathered to define common goals and standards. During the day the FSHD community presented the latest findings/data followed by a group discussion moderated by a multi-disciplinary panel of seven distinguished scientist which culminated in discussions to identify areas in need of development and funding in FSHD. During the planning components of the meeting all attendees collectively developed a list of future plans in the context of what we know now. [Executive Summary] Priorities as Stated by FSHD Research Community for FSHD Research: 2013 and Beyond. The summary and recommendations of the group state that given the recent developments in our definition of FSHD1A and FSHD1B [FSHD2] and there is a need to ramp up the preclinical enterprise and build/organize infrastructure needed to conduct clinical trials on FSHD1A and FSHD1B. Our immediate priorities should be to confirm the DUX4-fl hypothesis, if valid then understand normal DUX4 function, and finally, understanding the naturally occurring variability should allow us to manipulate the disease in our favor. We need to be prepared for this new era in the science of FSHD, by accelerating efforts in the following five areas: 1. Genetics / epigenetics. There is general acceptance that transcriptional deregulation of D4Z4 is central to FSHD1 and FSHD2. The FSHD2 gene SMCHD1 explains approximately 80% of FSHD2. There is a need for better understanding of the factors that modulate DUX4 activity and disease penetrance. 2. FSHD molecular networks. D4Z4 chromatin relaxation on FSHD-permissive chromosome-4 haplotypes leads to activation of downstream molecular networks. In addition to considering DUX4 as the “target” and downstream targets, the upstream processes and targets – triggering of activation – are equally important. Hence, understanding what DUX4lf does as a target and targets up- and down-stream of it are priorities. Detailed studies on these processes are crucial for insight in the molecular mechanisms of FSHD pathogenesis and may contribute to explaining the large intra- and interfamily clinical variability. Importantly such work may lead to intervention (possibly also prevention) targets. Additional FSHD genes and modifiers are still likely to exist. Apart from chromatin modifiers, these include, but are not limited to, CAPN3 and the FAT1 gene that was recently suggested to be involved in FSHD. 3. Clinical trial readiness. It is now broadly accepted that deregulation of the expression of D4Z4 / DUX4 is at the heart of FSHD1 and FSHD2. This finding opens perspectives for intervention along different avenues. Intervention trials are envisaged within the next several years. The FSHD field needs to be prepared for this crucial step. There is an increasing need to improve the translational process. This includes, but is not limited to, the need for consensus on data capture and storage, overcoming national and international barriers, definition of natural history, identification of (meaningful) and sensitive outcome measures, biomarkers, and meaningful functional measures. There is a need to work more closely with FDA to help define acceptable measures for trials. 4. Model systems. There was already a good set of cellular and models, based on different pathogenic (candidate gene) hypotheses. This was further expanded during the last year. The phenotypes are very diverse and often difficult to compare with the human FSHD phenotype. Many basic questions remain unanswered and dearly need to be answered for further translational studies: when and where is DUX4 expressed in skeletal muscle and what regulates DUX4 activity. It was recognized that there still exists a gap in our knowledge linking the basic genetic and molecular findings with the observed muscle pathology. The BBRI NIH Sen. Wellstone center and the Fields Center continue to generate human cellular resources. These resources continuously deserve attention and need to be replenished. Recent progress in ES-cell technology, including iPS lines, allows for inter-group distribution and dedicated molecular (epi)genetic studies. 5. Sharing. Timely sharing of information and resources remains a critical contributor to the progress in the field. Wellstone and Fields Center continue to share their resources to the scientific community. The Fields Center website also continues to share other information (e.g. protocols, guide to FSHD muscle pathology, etc.). We thank you for your financial support of the FSH Society FSHD International Research Consortium Workshop to help foster significant progress in both collaboration on FSHD and our understanding and treating FSHD. Contacts: Daniel Paul Perez Rabi Tawil, M.D. Silvere van der Maarel, Ph.D. Title of event: Sponsored by: Phone: Fax: Date/Time: The 2011 International Research Consortium & Research Planning Meetings Were a Huge Success! Scientists, patients, advocates, biotech and pharmaceutical companies, and clinicians from throughout the world gathered at Boston Biomedical Research Institute (BBRI) on November 7-8, 2011, to attend the FSH Society 2011 International Research Consortium and Research Planning Meetings for facioscapulohumeral muscular dystrophy (FSHD). The FSH Society, co-organized the meetings that focused on collaborating to find new treatments and cures for FSHD, which is the most common adult form of muscular dystrophy affecting 1 in 14,000. Dr. Charles Emerson, Jr., distinguished scientist and Director of the Boston Biomedical Research Institute, and Co-Director, along with Dr. Louis Kunkel of Harvard Medical School and Children’s Hospital, of the NIH Eunice Shriver Kennedy NICHD BBRI Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center for FSHD, hosted the meeting at BBRI in Watertown, Massachusetts. Daniel Perez, President & CEO of the FSH Society, Watertown, Massachusetts served as the organizational chair. Silvère van der Maarel, Ph.D. (Leiden University Medical Center, Leiden, the Netherlands), was the European research co-Chair. Dr. Robert H. Brown, Jr, M.D., D.Phil. (University of Massachusetts Medical School UMASSMemorial, Worcester, Massachusetts was the American clinical co-Chair. Also joining the meetings were several muscular dystrophy program directors from the NIH: John Porter, Ph.D., program director for the NIH NINDS and Glen Nuckolls, NIH NIAMS. Other research directors attending the meeting were Dr. Paul Muhlrad of MDAUSA, Tucson, Arizona, Dr. Glen Pilkington of FSHD Global Research of Australia, Gillian Butler Browne, AFM, Paris, France, and Dr. Dan Miller of Friends of FSH Research, Seattle, Washington. All volunteer agencies working on FSHD were invited by the FSH Society and encouraged to attend. Over 95 researchers and clinicians from institutions, industry and funding agencies gathered from across the United States and around the world. It was a very successful workshop. And once again was better than the year before and really was "the place to be" for FSHD research. The atmosphere was very positive and constructive and all in attendance felt that it was one of the most productive meetings to date. Also was excellent to see that the interaction between all research groups and funding agencies, evidenced by several announcements and agreements to work jointly and corroboratively on projects. Also, excellent to see most all FSHD organizations working extremely well together side by side in the common front to solve and treat FSHD. Sponsors for the event included: Association Française Contre les Myopathies (AFM), FSH Society, FSHD Global Research Foundation, NIH Eunice Kennedy Shriver NICHD Boston Biomedical Research Institute Sen. Wellstone MDCRC, Muscular Dystrophy Association United States (MDAUSA) and Quest Diagnostics Athena Diagnostics. Together we reviewed last year’s research priorities and reprioritize them in light of recent developments. We also expanded on the format of the meeting. A series of topical discussions (working sessions) were each led by a pair of distinguished scientists whose role was to provide a stimulating overview of the topic and facilitate discussion. The meeting was a working meeting with experts, developing future plans in the context of what we know now. In the interest of time, we emphasized new data and ideas and to avoid restating data that has already been published. Click here to view the Suggested Topics for FSH Society FSHD Working Groups The goal of this meeting was to explore and verify the complex genetic mechanism and various features of FSHD, to allow us to move quickly to the development of potential treatments for FSHD. 2011 brought quite a significant increase in interest from government, non‐profit, and private agencies and a need for much more funding for FSHD. It has also ushered in an international collaboration of volunteer health agencies and FSHD patients working side‐by‐side with research and clinical communities. It is essential to keep going in this direction, and for the entire community to work together at every level to communicate clearly on programs, developments and needs. This year’s workshop participants included clinicians, scientists, biotechnology companies, pharmaceutical companies, government and non‐profit funding agencies, and patients – committed to solving, treating and curing FSHD at this workshop. Over the course of the two days the FSHD community presented the latest findings/data and had various breakout discussion groups and whole group discussions which culminated in discussions to identify areas in need of development and funding in FSHD. During the Planning components of the meeting all attendees collectively developed a list of future plans in the context of what we know now. In the interest of time, we emphasized new data and ideas and to avoid restating data that has already been published. Click here to view the Sponsors for the 2011 International Research Consortium & Research Planning Meetings The summary and recommendations of the group stated that given the recent developments in our definition of FSHD and the potential that within one to two (1-2) years, evidence-based intervention strategies, therapeutics, and trials being planned and conducted. Our immediate priorities should be to confirm the DUX4 hypothesis, if valid then understand normal DUX4 function, and finally, understanding the naturally occurring variability should allow us to manipulate the disease in our favor. The group stated that we need to be prepared for this new era in the science of FSHD, by accelerating efforts in the following four areas: Click here to view the full IRC Workshop 2011 Working Consensus of Tactical and Strategic Research Priorities for FSHD The international FSHD clinical and research community recently came together at the DHHS NIH NICHD Boston Biomedical Research Institute Senator Paul D. Wellstone MD CRC for FSHD. Almost 90 scientists working on FSHD globally met at the 2011 FSH Society FSHD International Research Consortium, held November 7-8, 2011. The summary and recommendations of the group state that given the recent developments in our definition of FSHD and the potential that within one to two (1-2) years, evidence-based intervention strategies, therapeutics, and trials being planned and conducted. Our immediate priorities should be to confirm the DUX4 hypothesis, if valid then understand normal DUX4 function, and finally, understanding the naturally occurring variability should allow us to manipulate the disease in our favor. We need to be prepared for this new era in the science of FSHD, by accelerating efforts in the following four areas: 1. Genetics / epigenetics FSHD molecular networks. The relaxation of the chromatin structure on permissive #4 haplotypes leads to activation of downstream molecular networks. Importantly, the upstream processes – triggering of activation – are equally important. Additional FSHD genes. FSHD2 is characterized by hypomethylation of D4Z4 on #4 as well as #10. This also leads to bursts of DUX4 expression. Identification of the responsible factor (gene) and molecular mechanisms is of utmost importance. This work will be facilitated by the recruitment of additional families. Also other genes need to be considered that may give rise to FSHD-like phenotypes. These include, but are not limited to, CAPN3 and the FAT1 gene that was recently suggested to be involved in FSHD. 2. Clinical trial readiness Clinical Trial Readiness. Intervention trials are envisaged within the next several years. The FSHD field needs to be prepared for this crucial step. To design and coordinate this important translational process, it was envisaged to install an international task force Clinical Trial Readiness (FSHD-CTR), with Dr Rabi Tawil as leader. The FSHD-CTR needs to be a multidisciplinary group, including members with expertise, not only in FSHD but also, in trial design and execution, statistics, (non-invasive) biomarkers etc. Important issues are: Biomarkers. Sensitive biomarkers are needed to monitor intervention: they might also improve diagnosis. Important to consider biomarkers established from easily accessible sources like blood. Non-invasive methods like imaging needs further attention. 3. Model systems FSHD Model Data Base. The importance of a systematic database was recognized. This DB should contain detailed information on the molecular characteristics of the model (design and phenotype). Particular emphasis should be paid to the muscle pathology. Non-muscle phenotypes – described also in FSHD patients deserves attention. Human pathology and bio-banking. Importantly, this DB should also contain well-documented muscle pathology data of patients – astonishingly difficult to find in the literature. Human cellular resources continuously deserve attention. Recent progress in ES-cell technology, including iPS lines, allows for inter-group distribution and dedicated molecular (epi)genetic studies. 4. Sharing We thank you for your financial support of the FSH Society, Inc. and its research programs to make such significant progress possible. Current and previous year's program and abstract booklets can be obtained here: 2011 Watertown, Massachusetts
1. Shareable Protocols. There is a need for access to FSHD research protocols and experimental methods by FSHD researchers internationally. Needed are available, clear and well defined research protocols to allow verification, standardization and corroboration of research findings and publications. 2. Common and shareable materials and data by whole community. There is a need for global and international biomaterials and data management. Needed are schemas to identify source and context of biomaterials and data, meaningful data identifiers, and easily accessible bio-repositories and data sources. 3. Corroborate and verify DUX4 finding. This line of work will be instrumental to pinpoint the real identity of FSHD1A (chromosome-4-D4Z4-contraction-linked cases) and FSHD1B (chromosome-4-non-D4Z4-contraction-linked cases & non-chromosome-4-linked cases). This information will form the basis for evidence-based intervention. There is a need to verify and reproduce the DUX4 finding using multiple sites and patient materials. 4. FSHD alleles in context of population genetics need to be defined. There is a need to understand the normal function of the short DUX4 transcript in every human being and the abnormal function of toxic long-form of the DUX4 transcript. 5. Biomarkers. There is obvious need for monitoring intervention. There is the need to define biomarkers for clinical trials endpoints, to understand the FSH disease at multiple omics levels and to understand pathways and signaling of FSHD through “omics” analysis 6. FSHD clinical evaluation scales/systems need be defined under one agreed standard. There is an important need to have a comprehensive and single clinical evaluation standard to allow a list of clinical identifiers and parameters to be assembled into a thorough and robust dataset. This can be applied to subsequent systems biology and –omics areas. 7. Working Groups / Mouse model working group consortium. There is a need for models and methods to interpret the current mechanistic paradigm of FSHD and fidelity of current data. What is needed is an assessment of various modeling approaches. Short and near-term we need consensus on the limits and capabilities of current modeling approaches. 8. Model systems for mechanistic, intervention work and advancement to clinical trials. We need to be able to understand the limits of the both data and models. There is the need to address the complexity of FSHD in the context of mammalian systems. It becomes even more important to have a solid model and dataset to test. 9. Epigenetics / Genetics. There is the need to further evaluate FSHD1, FSHD2 and phenocopies using the genetic approach. Resolve and establish genes involved in the pathophysiology of FSHD (DUX4, FRG1, FRG2 and other 4q35 loci, PitX1, Pax3, Pax7 and other impacted distributed loci, related cascades and pathways, etc.) 10. Clinical trials readiness. There is a need to revisit we know about the pathological progression We thank you for your financial support of the FSH Society, Inc. and its research programs to make such significant progress possible. N.B. During the 2010 meeting Ljubisa Vitkovic, Ph.D., program director for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) gave a seminar on “NIH Grants Workshop For Beginners (the art of writing, targeting and revising applications, and developing a relationship with NIH).” This was especially targeted for junior investigators who are applying for their first NIH grants or have limited experience with the NIH. TEXT SIZE
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FSH Society, Inc. • 450 Bedford Street • Lexington, MA 02420 • Tel: 781 301-6060 • Fax: 781 862-1116
Annually since 1994, the FSH Society has held the FSHD International Research Consortium Workshop for researchers and clinicians involved with FSHD. This meeting is one day in length and is held as a satellite meeting to the annual American Society of Human Genetics (ASHG) meeting or as an annual meeting of the DHHS NIH NICHD BBRI Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center for FSHD, in Watertown, Massachusetts. This meeting is the primary annual platform for clinicians, medical researchers and basic scientists to present and discuss new developments in FSHD research, reinforce collaborative efforts and facilitate new initiatives.