Friday, November 13, 2015

Neuroscience Center
Conference Room C/D
Bethesda, Maryland

Meeting Agenda


Welcome and Introductions

Steve Katz, Acting Chair MDCC


Conflict of interest, committee management, general info

Glen Nuckolls, Executive Secretary MDCC


Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Catherine Spong, Acting Director NICHD


MDCC Action Plan: Member Organization Mission Landscape and Progress Monitoring

Glen Nuckolls


Discussion of Action Plan mission landscape and progress monitoring

Committee members and meeting participants

10:25 Break

MDF Patient-Centered Therapy Development Meeting Report

Sharon Hesterlee, Myotonic Dystrophy Foundation


FSHD Trial Readiness Meeting Report

Rabi Tawil, University of Rochester


FDA Biomarker Qualification Program

Shashi Amur, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration




Imaging Biomarkers for the Muscular Dystrophies

Krista Vandenborne, University of Florida


Biochemical Biomarkers for the Duchenne Muscular Dystrophies

Yetrib Hathout, Children’s National Medical Center, DC


Discussion of the development and qualification of biomarkers and outcome measures for the muscular dystrophies

MDCC members and meeting participants

2:55 Break

NIH Office of Rare Disease Research

Petra Kaufmann, Director ORDR, NCATS

3:35  Comments from the public, in the room and calling in
4:10 Vote on nomination of MDCC Chair for 2016-2017

Summary of action items, closing remarks

Steve Katz

4:30 Adjourn


Call to Order and Opening Remarks
Reports from Federal Agencies
Updates from Recent Meetings and Workshops
Biomarkers for the Muscular Dystrophies
NIH Office of Rare Disease Research
Public Comment and Conclusion

The Muscular Dystrophy Coordinating Committee (MDCC) met on November 13, 2015, at the Neuroscience Center in Bethesda, Maryland. Stephen I. Katz, M.D., Ph.D., Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), served as Acting Chair in place of Dr. Alan Guttmacher, former Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), who retired from the NIH. Dr. Glen Nuckolls, Program Director, National Institute of Neurological Disorders and Stroke (NINDS), served as Executive Secretary. The entire meeting was held in open session and was in accordance with Public Law 92-463.

Call to Order and Opening Remarks

Dr. Katz called the meeting to order. Following introductions of those in attendance and those participating by phone, he presented a broad overview of NIH-wide activities and the meeting agenda.

Dr. Nuckolls reviewed the conflict of interest disclosure requirements for committee members and provided an update on current membership. 

Reports from Federal Agencies

Dr. Catherine Spong, Acting Director of NICHD, presented an overview of NICHD’s support for research on the muscular dystrophies and related areas. The NICHD’s muscular dystrophy research investments fall largely within the Wellstone Center at the University of Massachusetts, with additional investments in pediatric developmental pharmacology, investigator-initiated projects, training grants, and newborn screening efforts. Dr. Spong also highlighted NICHD’s participation in the IDeA States Pediatric Clinical Trials Network, which will build upon the existing Institutional Development Awards (IDeA) program that supports faculty development and research infrastructure in geographic areas where NIH funding has been historically low. MDCC members were particularly interested in the new IDeA States program because it might enable individuals and families who reside in rural areas to participate more readily in clinical research.

Dr. Nuckolls presented an update on the 2015 Action Plan for the Muscular Dystrophies, a document that provides an outline of the priority needs for improving treatments and reducing the impact of all types of muscular dystrophies. Prior to the meeting, a supermajority of the MDCC voted to approve the 2015 Action Plan for the Muscular Dystrophies, with the FDA abstaining, pending further review. In follow-up to a discussion at the March 2015 MDCC meeting, Dr. Nuckolls provided a distillation of information regarding the relevance of the various Action Plan objectives to member agencies and organizations.  Analysis of information provided by MDCC members revealed that almost all of the 81 objectives and goals of the Action Plan fall within the mission of one or more member agency or organization, and there are many opportunities for collaboration.  Dr. Nuckolls presented a plan to collect information from MDCC members regarding their agencies’/organizations’ support for efforts according to five Action Plan priorities that summarize the 81 objectives and goals. This data would be collected and reviewed annually to track efforts addressing the Action Plan as well as to monitor the muscular dystrophy workforce.

An open discussion on strategies for monitoring progress on the Action Plan followed. There was wide-spread support for developing a system to collect data and report on MDCC member investments on the five Action Plan priorities and for monitoring the growth and stability of the research workforce. The feasibility of collecting and reporting this data for each of the MDCC members was discussed, with many members reporting they already have systems in place to accomplish similar tasks. Interest in expanding this data collection effort to the broader muscular dystrophy community was discussed.  This might be pursued after first piloting the project with current MDCC members. The need to better communicate the activities of the MDCC to the wider muscular dystrophy community was also discussed and a tentative plan to develop a communications subcommittee of the MDCC was introduced. 

Updates from Recent Meetings and Workshops

Dr. Sharon Hesterlee, Chief Science Officer, Myotonic Dystrophy Foundation (MDF), provided an overview of a recent meeting on “Myotonic Dystrophy Patient-Centered Therapy Development” held in September 2015 in Arlington, Virginia. After providing a brief introduction to myotonic dystrophy and the MDF, Dr. Hesterlee summarized several topics covered at the meeting, including studies collecting data on how patients perceive the balance of benefits and risks in clinical trials, ways to advance the science of collecting and interpreting patient input, efforts to identify clinically meaningful endpoints, develop outcome measures, and identify biomarkers for the myotonic dystrophies. The MDF is preparing a meeting summary for publication.

Dr. Rabi Tawil, University of Rochester Medical Center, summarized a recent workshop on FSHD Trial Preparedness held in May 2015 in Rochester, New York. After providing a brief background on facioscapulohumeral muscular dystrophy (FSHD), Dr. Tawil highlighted some of the main topics of the workshop, which included recruitment of patients for clinical trials, development and validation of clinical outcome measures in FSHD, and progress and challenges in establishing the reliability and reproducibility of tissue, serum, functional, and imaging biomarkers.

Mr. Daniel Perez, CEO, FSH Society, provided an overview of the 2015 FSHD International Research Consortium meeting held in Boston, Massachusetts. Priorities discussed at the meeting included the importance of identifying bottlenecks to therapy development, research into genetics and epigenetics, and continued development and validation of pre-clinical models. Mr. Perez also mentioned the FSHD Champions International Research Consortium. Discussion following Mr. Perez’s and Dr. Tawil’s presentations centered on current limitations and the need for well validated outcome measures. 

Biomarkers for the Muscular Dystrophies

Dr. Shashi Amur, Scientific Lead for the Biomarker Qualification Program, FDA, presented a talk on the FDA’s Biomarker Qualification program.  Biomarkers are indicators of normal biological or pathogenic processes, or responses to therapeutic intervention that can be objectively measured.   They are integrated into the drug development process at FDA either through individual drug review programs or via the FDA Biomarker Qualification Program, which then allows use of the biomarker for the qualified context of use in multiple drug development programs. Biomarker qualification involves initial contact, acceptance of the biomarker project into the program and consultation with the FDA followed by review of data supporting the biomarker’s reliability in a specific context of use. While biomarker qualification is not required for use of biomarkers in drug development, qualification offers a pathway to establish the use of a biomarker(s) in multiple drug development programs without further FDA review for the qualified context of use.

Dr. Krista Vandenborne, University of Florida, provided an update on the progress of the Imaging DMD study, a natural history study aiming to validate magnetic resonance imaging and spectroscopy biomarkers for Duchenne muscular dystrophy (DMD), for use in clinical trials. To date, Dr. Vandenborne and her team have acquired high-quality and consistent quantitative data on secondary pathological features in DMD. A specific biomarker used is the relative amount of fat and water within the lower leg muscles, with fat fraction increasing as the disease progresses. The techniques can detect the beneficial effects of corticosteroids and can detect progression of the disease before patients begin to lose function. The next steps in the project are to extend to studies of the upper limb, assemble an infrastructure for widespread sharing of MRI and functional data, incorporate the measures into clinical trials (currently being used in three), and begin discussions with the FDA regarding qualification of fat fraction as a biomarker in DMD.

Dr. Yetrib Hathout, Children’s National Medical Center, presented research his group is conducting into biochemical biomarkers derived from blood from individuals with DMD. A current challenge in therapy development is that different outcome measures are required at different stages of disease, and these measures can sometimes be subjective and lack sensitivity. Dr. Hathout’s group collected serum from multiple mouse models of DMD and from individuals with DMD and looked for changes in the levels of different proteins. This group identified several candidates, and they are further validating the findings. Because of the inherent difficulties in measuring and localizing dystrophin as a biomarker itself, these additional protein biomarkers from serum may offer alternatives.

Discussion following the presentations on biomarkers centered on how biomarker development and qualification can be advanced for all muscular dystrophies. The need for biomarkers to be reproducible with repeated measures was also stressed. Dr. Nuckolls described a new NINDS funding opportunity (PAR-16-020) to support clinical trial readiness (including biomarker and outcome qualification) for rare neurological and neuromuscular diseases which includes the muscular dystrophies. 

NIH Office of Rare Disease Research

Dr. Petra Kaufmann, Director, Division of Clinical Innovation and the Office of Rare Diseases Research, provided an overview of how the National Center for Advancing Translational Sciences (NCATS) is expediting translational research. NCATS has initiatives to streamline multi-site clinical trials and to improve patient recruitment and research infrastructure. Dr. Kaufmann also presented an update on the Rare Disease Clinical Research Network, or RDCRN . This unique network provides, among other data, observational and natural history information critical for the evaluation of potential therapies, and often includes patient advocacy group support. Overall, NCATS is strengthening network capacities, promoting partnerships and training, and facilitating coordination among researchers by leveraging major resources including the Clinical and Translational Science Award (CTSA) Program and the RDCRN. Discussion following Dr. Kaufmann’s presentation included how the new IDeA program introduced by Dr. Spong relates to the CTSA program, and whether NCATS is working to facilitate international clinical trials, which can be especially important for rare diseases. 

Public Comment and Conclusion

Ms. Annie Kennedy, Parent Project Muscular Dystrophy, proposed a future meeting topic on issues of access to care and resources for individuals living with muscular dystrophy.

Dr. Katz provided final concluding remarks and a summary of the meeting’s proceedings, including plans to publish an executive summary of the Action Plan, establish an approach for gathering information about activities relating to the Action Plan MDCC members are supporting, and form a new working group to communicate the activities of the MDCC. Future meeting topics may include public-private partnerships in the muscular dystrophies and access to care and services for individuals with muscular dystrophy. The next meeting is tentatively scheduled for April 27, 2016.

The meeting concluded with selection of the next MDCC Chair. Following Dr. Katz’s nomination, a vote was taken and was unanimous in approving Dr. Katz’s nomination.


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