Department of Health and Human Services
National Institutes of Health
Muscular Dystrophy Coordinating Committee
June 25, 2007
The Interagency Muscular Dystrophy Coordinating Committee (MDCC) was convened for its sixth meeting on June 25, 2007 at the Crowne Plaza Hotel, Silver Spring, MD. Dr. Stephen Katz, Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), served as Chairperson and Dr. John Porter, Program Director, National Institute of Neurological Disorders and Stroke (NINDS) served as Executive Secretary. In accordance with Public Law 92-463, the entire meeting was held in open session.
Table of Contents
Dr. Stephen Katz called the meeting to order at 8:09 am. He welcomed the Committee members and noted that this committee facilitates coordination of muscular dystrophy programs across Federal agencies and in partnership with advocacy groups. A key purpose of MDCC meetings is to review what each agency is doing in response to the Action Plan for the Muscular Dystrophies. The Action Plan was developed by a Scientific Working Group in August 2005, approved by the MDCC in December 2005, and serves as a focus for coordinating the activities of MDCC agencies and organizations. Dr. Katz noted that this meeting would also review new initiatives and partnerships among MDCC members and introduce the NIH Workshop on Translational Research in Muscular Dystrophy that immediately followed the MDCC meeting. He welcomed public questions and comments both during the meeting and in a public comment session at the end, in accordance with the guidelines for Federal Advisory Committee Act (FACA) committees. Minutes of this meeting will be posted on the MDCC web site.
Dr. James Hanson, representing the Director of the National Institute of Child Health and Human Development (NICHD) and Dr. Gail Pearson, representing the Director of the National Heart Lung and Blood Institute (NHLBI), both summarized their ongoing commitments to research in muscular dystrophy and indicated their appreciation of Committee members efforts and of the MDCC's activities.
Dr. Story Landis, Director of the NINDS, added her appreciation of the Committee's efforts at a later point in the meeting. At that time, she pointed to the NINDS translational research program, now 5 years old, that addresses the gap between basic science discoveries in the lab and approval of Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications to the Food and Drug Administration (FDA). Dr. Landis noted that these translational grant and cooperative agreement mechanisms represent an important component of NIH's efforts to advance therapies in the muscular dystrophies. She also introduced Dr. Walter Korshetz, a board-certified neurologist who formerly was the Vice Chair of Neurology at Massachusetts General Hospital, as the new Deputy Director of NINDS.
Dr. Katz noted recent changes in Committee membership, including the addition of Dr. Michele Lloyd-Puryear, Chief of the Genetic Services Branch, Maternal and Child Health Bureau, Division of Services for Children with Special Health Needs, representing the Health Resources and Services Administration (HRSA), and Dr. Pam Costa, the Acting Director of the Division of Human Development and Disability at the Centers for Disease Control and Prevention (CDC) and is acting MDCC representative for the CDC. Dr. Katz also noted that Mr. Steve Tingus, the Department of Education (DoEd) representative, had just moved to the Office of the Secretary of Health and Human Services, resulting in a vacancy for the DoEd position on the MDCC. The Center for Medicare and Medicaid Services (CMS) position remains vacant, as they have not yet nominated a replacement for the MDCC.
Committee and audience members briefly introduced themselves.
Dr. Porter, Executive Secretary for the MDCC, reviewed the conflict of interest policies and procedures and ensured that Committee members had signed conflict of interest disclosures.Top
Dr. Porter briefly reviewed the history, organization, and contents of the MDCC Action Plan for the Muscular Dystrophies that the Committee put into place in December 2005 http://www.ninds.nih.gov/find_people/groups/mdcc/MDCC_Action_Plan.pdf. He noted that the Action Plan was assembled with the help of an expert panel to serve as a coordinating focus for the MDCC.
Recent data on Congressional appropriations for the NIH were reviewed, noting that the doubling of the NIH budget ended in 2003 ($13.7B in FY1998 to $27.1B in FY2003) and that since 2003 growth had been relatively flat (to $28.6B in FY2007). It was noted that the large majority of NIH funding is in response to investigator-initiated applications, with the scientific merit ranking of applications done by review panels (study sections) comprised of extramural scientists. The NIH goal is that the best science is funded, with the funding level for a specific disease largely influenced by the number and quality of applications submitted by extramural scientists. Although a pay line established on the basis of study section rankings determines funding for the majority of applications, Dr. Katz noted that most NIH institutes have select pay mechanisms where factors such as institute mission and unmet scientific and medical needs (e.g., underserved areas, high risk/high reward science, etc.) contribute to funding decisions. NIH initiatives, such as those described below, also are used to solicit applications in specific areas and to target support to particular needs.
Overall NIH support for research in muscular dystrophy was approximately $40M in FY2006, with the growth rate roughly reflecting that of the overall NIH budget. By disease, approximately $18M was for Duchenne muscular dystrophy (DMD), $2M for facioscapulohumeral muscular dystrophy (FSHD), and $7M for myotonic dystrophy (DM). NIH support figures by disease are tabulated annually at the end of the Federal fiscal year (September 30). Figures for FY2007 should be available by January 2008. Nine NIH institutes (NIAMS, NINDS, NICHD, NHLBI, National Cancer Institute (NCI), National Institute on Aging (NIA), National Institute for Nursing Research (NINR), National Human Genetics Research Institute (NHGRI), and National Center for Research Resources (NCRR)) funded research relevant to muscular dystrophy in FY2006.
The distribution of NIH funding for the muscular dystrophies in FY2006, by components of the MDCC Action Plan, was: 45% for disease mechanisms, 5% for diagnosis and screening, 39% for therapy development, 1% for living with muscular dystrophy, 8% for infrastructure, and 2% unclassified (primarily pilot projects supported by the NCRR General Clinical Research Center (GCRC) or Clinical and Translational Science Awards (CTSA) for which project abstracts are unavailable).
Dr. Porter reviewed several continuing NIH initiatives that are targeted to muscular dystrophy for training, career development, and studies on disease pathogenesis and treatment development; plus new initiatives for research on Nuclear Structure-Function Defects in Muscular Dystrophy for FSHD, Emery-Dreifuss (EDMD), and oculopharyngeal muscular dystrophies (OPMD) and the renewal of the Senator Paul Wellstone Muscular Dystrophy Cooperative Research Centers (MDCRC).
The NIH Translational Research in Muscular Dystrophy program was launched in November 2005, using a milestone-driven funding model, special review environment, and extensive NIH staff involvement to facilitate preclinical therapy development. This translational program was responsive to recommendations of the MDCC Action Plan. The program has enjoyed significant success, with funding of approximately $30M (total costs, all years) for cooperative agreements and research grants with FY2007 start dates. Dr. Katz noted that even though these awards are substantial, this is an early stage therapy development effort and considerable more funds will be needed before a new drug is approved by the FDA.
Awards in the NIH translational program are designed to fund preclinical therapy development up to and including the stage of an IND application to the FDA that would allow the initial clinical trials to start. The goals of recent awards in the NIH Translational Research in Muscular Dystrophy program include development of small molecule-based drugs for both DMD and other muscular dystrophies, regional delivery of gene therapy for DMD, engineering new viral delivery systems for gene therapy in DMD, protein-based therapy for DMD and a form of congenital muscular dystrophy (CMD), and development of drug therapies for DM. Dr. Porter emphasized the importance of collaborations among MDCC agencies and organizations in therapy development, noting that one of the large cooperative agreements recently funded through the translational program was made possible by pilot studies funded by Parent Project Muscular Dystrophy (PPMD). Ms. Patricia Furlong added that the funding of this cooperative agreement demonstrates the need for and value of collaborations throughout the muscular dystrophy community, in order to develop new treatments, and that she viewed the MDCC as an excellent vehicle for formation of these essential collaborations.
Dr. Hanson raised the issue that the term, 'translational research,' carries different meanings. Dr. Katz acknowledged this, noting that some use this terminology to cover all activities from bench-to-bedside in therapy development, while the NIH initiative targeted to muscular dystrophy used the term in a more restricted manner for preclinical therapy development-from target identification through an IND application. Dr. Hanson noted that therapy development is really about bench-to-bedside-and-back, with experience in the clinic necessarily informing future basic science research directions in a cyclic process that is essential to optimizing therapies.Top
As a consequence of recommendations in the MDCC Action Plan, the NIH and the Muscular Dystrophy Association (MDA) partnered to issue Requests for Applications (RFAs) for mechanistic studies on a set of muscular dystrophies where understanding is currently insufficient. These muscular dystrophies appear to share involvement of structure and/or function of the muscle cell nuclei (FSHD, EDMD, and OPMD), raising the possibility that studies on any one could have synergistic benefit for the other diseases. In contrast to muscular dystrophies that have their primary defects in the muscle surface membrane or sarcolemma (DMD, CMD, and some limb girdle muscular dystrophies) and have targeted translational research well underway, the current understanding of disease mechanisms in these muscular dystrophies represents an obstacle to targeted therapy development. The specific recommendations that were acted on to produce these RFAs, and improve understanding of FSHD, EDMD, and OPMD, can be found in the Disease Mechanisms component of the Action Plan, under Disease-Specific Mechanisms section. Dr. Porter reviewed the rationale, goals, and robust response to the RFAs.
Drs. Porter and Glen Nuckolls (NIAMS) briefly reviewed the three research grants on FSHD, two on EDMD, and one on OPMD that NINDS and NIAMS funded through the RFAs.
Dr. Sharon Hesterlee then described the MDA's involvement in the RFAs, noting that the MDA evaluated the NIH applications and study section reviews in making these additional funding decisions. The MDA funded one research grant on EDMD and two on OPMD.
Mr. Daniel Perez expressed the concern that in Congress, and even in the scientific community, 'muscular dystrophy' is often considered synonymous with 'DMD,' while the adult dystrophies, such as FSHD and DM, are relatively ignored. He was concerned that this mentality could negatively affect research support for the adult muscular dystrophies. Dr. Katz noted that that was not the usage of the 'muscular dystrophy' terminology within the MDCC, that the explicit charter of the MDCC was to promote research in all types of muscular dystrophy, and that the goal of the RFA under discussion was to promote research in a disease class that included FSHD and DM.
Dr. Katz remarked that strong interactions have existed between the NIH and MDA and that efficiency and trust was shown in this joint initiative. The synergy demonstrated by the partners shows the potential for further MDCC member collaborations to target needs identified by the MDCC Action Plan. Through the collective efforts of the NIH and MDA, investigators were given the two opportunities to obtain research funding from a single application and three new research projects have been launched in each of the muscular dystrophies that were targeted by the joint initiatives.Top
Dr. Nuckolls noted that the six existing Wellstone MDCRCs represent the NIH centers of excellence program in muscular dystrophy and that they constituted about 25% of the total NIH investment in muscular dystrophy in FY2006. He reviewed some of the recent scientific advances from research at the Wellstone MDCRCs, including how these advances relate to the objectives of the MDCC Action Plan. He also discussed the continued NIH commitment to the MDCRCs. A public web site has been developed by the NIH for the Wellstone MDCRCs (http://www.wellstonemdcenters.nih.gov/); information about the ongoing activities, preclinical and clinical studies, and shared resources available through each MDCRC may be found on the web site.
As examples of productivity from the Wellstone MDCRCs, Dr. Nuckolls reviewed several recent publications from MDCRC investigators that have direct bearing on MDCC Action Plan Objectives.
A comprehensive gene expression profiling (microarray) study of FSHD patient biopsies at the University of Rochester suggests a mechanistic linkage between skeletal muscle wasting and vascular defects, raising new hypotheses about the pathogenesis of FSHD. Notably, subject samples for this study came from the National Registry for Myotonic Dystrophy and FSH Patients and Family Members, supported by NIAMS and NINDS. This publication addresses Disease Mechanism objectives in the MDCC Action Plan.
A publication from the University of Washington MDCRC documents optimization of viral gene therapy. While a robust immune response has been an obstacle for gene therapy studies in the dog muscular dystrophy model, this recent study established a brief immunosuppression regimen to increase efficiency of gene delivery. This publication addresses Therapy Development objectives in the MDCC Action Plan.
Collaboration between the University of Iowa and University of Pittsburgh Wellstone MDCRCs led to a publication that characterized the nature and frequency of mutations responsible for limb girdle muscular dystrophy, comparing protein analyses of muscle biopsies with genetic testing of peripheral blood. This work has direct bearing on the specificity of diagnostic approaches, with strong relevance to the Diagnostic and Screening objectives of the MDCC Action Plan.
Progress has been made in clinical trials supported through the Wellstone MDCRC program. Dose escalation (safety and tolerability) studies of IPLEX (IGF1 complexed with IGFBP3) in DM have enrolled subjects and are well underway at the University of Rochester MDCRC, with completion expected in Spring 2008. Safety and tolerability studies of a protease inhibitor (Bowman-Burke Inhibitor Complex or BBIC) for DMD will be initiated in Fall 2007 at the University of Pennsylvania/Johns Hopkins University/NINDS MDCRC. This study also will examine the feasibility of skeletal muscle MRI as an efficacy measure for future clinical trials. Finally, a safety and feasibility study of gene therapy in limb girdle muscular dystrophy (LGMD) type 2D will soon be initiated through the University of Pittsburgh MDCRC. This trial also represents collaboration between MDCC members, with support from NIAMS and the MDA. Mr. Donovan Decker indicated enthusiasm for the LGMD trial; he has LGMD and was involved in a prior gene therapy trial. Finally, trials run by The Cooperative International Neuromuscular Research Group (CINRG) receive infrastructure support for the Children's National Medical Center MDCRC. Collectively the clinical studies and trials supported at Wellstone MDCRCs address several objectives in the Therapy Development component of the MDCC Action Plan.
Dr. Nuckolls noted that the collaborative/pilot program initiated via set-aside funds in the Wellstone MDCRCs has initiated several exciting new projects. Among these studies are projects for stem cell-based therapeutics, optimization of gene therapy, and assessment of myostatin inhibition strategies in the dog muscular dystrophy model. Three newly funded projects address the cell and molecular mechanisms of FSHD and two others are pursuing preclinical therapy development in DM.
Finally, Dr. Nuckolls reviewed NIH's plan for the Wellstone MDCRC competition in FY2008. The initial three Wellstone MDCRCs are up for renewal and will do so in competition with new applicants. The new RFA has been issued, with NIAMS, NINDS, and NICHD each planning to support an MDCRC and NHLBI is now involved in the RFA to provide co-funding of meritorious cardiorespiratory-related projects in an MDCRC. The emphasis with the new competition is on multi-disciplinary collaborations on therapeutic development projects that are not easily done with traditional NIH funding mechanisms. Each MDCRC is expected to have mechanisms for direct interactions between investigators and patients. In this round of applications, greater emphasis is being placed upon education and outreach, along with a new requirement for a training core.
Dr. Hesterlee asked whether NIH planned a formal evaluation of the MDCRC program and how success would be measured. Dr. Nuckolls noted that an informal evaluation was done during the process of developing the new RFA. Dr. Landis commented that NINDS has an ongoing evaluation of the Udall Centers program for Parkinson's disease research and stated that lessons learned from that process could be provided by the NINDS to inform a Wellstone MDCRC evaluation. Dr. Katz stated that additional guidance regarding center program evaluations would be forthcoming based upon the NIH Reauthorization Act. In response to questions, Dr. Hesterlee noted that the MDA had supported the first three Wellstone MDCRCs for three years at a total cost of approximately $1.5M/year and had no plans to reactivate that commitment.Top
Ms. Pamela Costa provided the Committee with an update of ongoing activities in DMD and Becker muscular dystrophies at the CDC. Through MD STARnet, the CDC funds five states and/or areas within states to do active case surveillance of individuals with DMD. These activities address objectives in the Screening and Diagnosis component of the MDCC Action Plan. As of May 2007, 716 medical records have been abstracted and 422 were determined as definitive DMD/BMD. In-depth information collection from parents of confirmed cases has been initiated to better assess the natural history of DMD. One clear trend is the decrease in muscle biopsies as molecular diagnosis becomes more entrenched. Preliminary analyses of public health surveillance data from one MD STARnet site suggest that steroid use prevalence at any point during a patients lifetime is only about 50% (272 of 476 cases), with approximately 18% of patients on steroids at any one time. Preliminary MD STARnet data were consistent with prior reports of prolonged duration of ambulation for those on steroids.
Mr. Perez asked about the nature of the data collection within MD STARnet. Ms. Costa replied that data were collected through public health surveillance activities, similar to the CDC's screening for birth defects, and that such public surveillance activities were anonymous and did not require informed consent.
Ms. Costa reported that the DMD care considerations project was ongoing, with the goal of determining the best practices for patient care from the existing scientific literature. Expert panels have been using the Rand appropriateness method to discern standards in the areas of diagnosis, rehabilitation management, respiratory, orthopedic, psychosocial, neurological, and cardiac care. In the absence of definitive patient care guidelines in some areas of practice, the goal of this CDC effort is to develop care considerations for patients, parents, and health care providers. These care considerations are to be based upon review and consolidation of the best existing scientific evidence, that may or may not yet been assimilated into clinical practice. The individual expert panels of the care considerations project worked extensively via electronic communications, met face-to-face between April and June of 2007, and it is anticipated that final reports will be completed during 2008.
The CDC is also working on publications of extensive studies of DMD patient mortality and of heart health in female DMD carriers. Ms. Costa also mentioned a newborn screening project that is being conducted in association with the Genetic Alliance, Emory University, and the Columbus Children's Research Institute, an outreach and education project conducted in partnership with PPMD, and a muscular dystrophy registry project. The CDC is currently examining software options and evaluating existing registry efforts (e.g., cystic fibrosis, oncology, and myotonic dystrophy) for lessons learned in order to facilitate the DMD registry project.
Mr. Perez questioned the interchanging use of 'muscular dystrophy' with 'DMD.' Discussion between Mr. Perez and Dr. Katz focused on the relative importance of the semantics of the terminology, and the need for public and physician education on the various types of muscular dystrophy, versus the question as to whether the CDC should extend its registry efforts beyond DMD. Ms. Costa pointed out that there are approximately 6,000 single gene disorders and that translatable solutions to deal with inherited diseases on a large scale are desirable.
A general public participant asked about potential consolidation of the multiple existing DMD registries on a global level. A key concern is that parents currently believe their children must be registered in several places in order to not miss access to information and clinical trial opportunities. Ms. Costa pointed to the upcoming United Parent Project Muscular Dystrophy (UPPMD) meeting where just such a consolidated registry was to be discussed. Ms. Furlong briefly described the organization and goals of the UPPMD meeting and remarked that the intent was to arrive at a core set of common data elements that are collected in the same way by all registries, and to potentially link the silos of information that are now collected in country-specific registries. Dr. Katz noted that the National Center for Biotechnology Information (NCBI) could add to this process and Ms. Furlong confirmed that they were already involved in discussions with NCBI over the DMD registry effort. Dr. Hanson commented that it may be unaffordable to institute registries at the rate of one disease or disease group at a time and that a common solution for inherited diseases would be desirable.
Another concern expressed by a public attendee related to the data that only 18% of DMD patients were receiving steroids at any given time; the attendee questioned whether scientific information on benefits of steroids (and other therapeutics and management guidelines) was being adequately communicated. Ms. Costa indicated that public health surveillance system data are typically published and results subsequently picked up for further dissemination and use by patient advocacy groups and physicians. Dr. Katz remarked that the NIH also uses the mechanism of press releases to disseminate research findings relating to therapies and clinical practice, but that translating scientific knowledge gained in research into clinical practice standards is often a difficult challenge. Ms. Furlong added the point that data access policies are critical-noting that registries should not silo data and unnecessarily restrict qualified individuals from access. The relationship of the level of information that is available in registries to national heath care policies (e.g., complete and in depth data availability in The Netherlands due to their national health care system) was discussed by Mr. Perez and Ms. Furlong.Top
Mr. Perez presented information on FSH Society efforts with respect to the MDCC Action Plan. He first noted that his organization had moved to an office within the Boston Biomedical Research Institute and has hired an executive director with extensive fund raising and development experience. The principal research support from the FSH Society goes through a formal application and peer review process toward both postdoctoral research fellow support and funding of early-stage, innovative research.
Mr. Perez organized his presentation by components of the MDCC Action Plan. He noted that FSH Society-funded efforts in Disease Mechanisms included particularly important studies on gene expression and chromatin structure. He noted particular opportunities, and the need for additional resources (potentially NIH R21 or R01 support), in the areas of gene expression, chromatin remodeling, reading across gene expression, chromatin structure, chromatin remodeling, allelic specificity, satellite repeats and beta-satellites, and junk (non-coding) DNA. He regarded these as areas where the pathogenic mechanisms of FSHD may be resolved given adequate funding and effort. Interesting findings regarding the D4Z4 region of the FSHD locus have come out of FSH Society-funded studies. These and other work has indicated a putative relationship between the PITX1 and PITX2 transcription factors, the D4Z4 locus, and FSHD candidate genes, DUX4, FRG1, and FRG2. Postdoctoral research fellows and junior faculty funded by the FSH Society are studying these candidate genes and putative regulatory mechanisms. He noted that some investigators previously funded by the FSH Society had received support through the NIH/MDA collaborative RFA for Nuclear Structure-Function Defects in the Pathogenesis of Muscular Dystrophy, while other investigators had not successfully competed for funding from this source. Mr. Perez noted that the FSH Society also has a substantial investment in model systems-funding the generation of 12 to 14 transgenic mouse lines. He provided examples of how the FSH Society is actively working with investigator by not only providing research funds, but encouraging particular lines of research and the collaborations and resource sharing necessary for progress in understanding disease mechanisms.
In relationship to the Diagnosis and Screening component of the MDCC Action Plan, the FSH Society has developed communication tools to ensure that patients are aware of available diagnostic tools.
Many of Action Plan-related Therapy Development efforts in FSHD are focused on identification of precise molecular targets for development of specific drug and biologic therapies-these target identification activities are summarized in the disease mechanisms section above. Mr. Perez noted that the FSH Society was working internationally to put Infrastructure into place to support clinical trials in FSHD, including efforts to identify biomarkers and validate them as surrogate markers for clinical trials.
Mr. Perez raised a concern that treatments for muscular dystrophy in general were lacking in the areas of physical, occupational, and respiratory therapy. As an example, he noted the tragic failure of physicians to recognize the interaction of sedatives with compromised respiratory function in muscular dystrophy that led to the death of an FSHD patient. The FSH Society has developed a physical therapy brochure with Shree Pandya and Wendy King to educate both patients and physicians.
Mr. Perez described how the FSH Society had worked extensively with Wyeth Pharmaceuticals to ensure inclusion of FSHD patients in the MYO-29 (myostatin inhibitor) clinical trial. He indicated that discussions also are underway with Acceleron Pharma about inclusion of FSHD patients in another clinical trial. Additional clinical studies that the FSH Society is associated with include collaboration with Nigmegen University looking at metabolic intramuscular heterogeneity using MRS and MRI.
In relationship to the Living with Muscular Dystrophy component of the MDCC Action Plan, Mr. Perez reviewed the FSH Society's efforts to promote dialog among patients, researchers, and clinicians through conferences that he regards as the centerpiece of the Society. The Society also maintains a natural history database, with several thousand individual registrants in approximately a thousand families.
Mr. Perez indicated that the FSH Society is looking at activities related to the Infrastructure objectives of the MDCC Action Plan, including developing vehicles for the collection and distribution of both tissue samples and animal models relevant to FSHD research.
In July 2006, the FSH Society convened a meeting to establish a detailed research plan for FSHD. Mr. Perez described the emphasis that the research plan has on resources, including cell lines, antibodies, animal models, and research funding. He noted that many of the areas that the Society is currently supporting are too novel and exploratory for standard NIH funding mechanisms. The FSH Society research plan emphasizes that mechanistic studies need to be expanded and broadened and it identified various areas that need more emphasis. Dr. Katz interjected that the NIH Roadmap was initiating efforts applicable to FSHD-the need to better understand epigenetics from the standpoint of not only what controls the epigenetic phenomena that are known but also to identify other epigenetic phenomena which we don't yet know. Mr. Perez continued to state the emphasis of the FSH Society upon collaborations; ensuring that researchers who are funded by the Society make the resources available to all of the other researchers, including mice strains, cell lines, antibodies, probes, and sequence information.
Mr. Perez noted that the FSH Society research plan would be put on-line. In addition, a process would be established on that web site for arbitrating scientific discrepancies (such as the controversy over FRG1 overexpression) and for cataloging resources and best practice recommendations. He indicated that an online journal of negative results might be of value for the FSH community, so that failed lines of research were not repeated. This is an important consideration given limited resources and funding. Mr. Perez then emphasized the importance of a national center for FSHD research, whether funded by an NIH program project grant (P01) or as a Wellstone Center.
Mr. Perez was asked about the genetic nature of FSHD and noted that many researchers believe it is a polygenic disease, but that it could be a disease of RNA. Dr. Hanson described NICHD efforts on the epigenetics of human development and that proposals for studies of FSHD would be appropriate as part of this effort. Dr. Katz reiterated his comment that epigenetic disorders, as FSHD appears to be, are being addressed in a new NIH Roadmap initiative and he encouraged FSHD researchers to take advantage of this opportunity.Top
Capt. Kaime first described the nature of the Congressionally Directed Medical Research Program (CDMRP)-that the Department of Defense (DoD) was explicitly directed by Congress to expend funds for specific diseases, and sometimes to allocate funds for specific researchers. The remainder of funding in the CDMRP appropriation then is used in open competition through investigator-initiated application, external peer review, and programmatic review processes. CDMRP support for research in muscular dystrophy has been in place since the 2003 fiscal year. She noted that there was substantial translational focus to many of the CDMRP-funded projects, and that these efforts were consistent with the Therapy Development objectives of the MDCC Action Plan.
Capt. Kaime described on-going CDMRP-funded research projects. The stem cell work for muscular dystrophy done by Johnny Huard (University of Pittsburgh) is synergistic with his collaborations on potential therapies for battlefield injuries with the Military Institute for Surgical Research, ISR. Dr. Huard's work on muscular dystrophy focuses on the feasibility of stem cell therapeutics-isolation of stem cells from subjects with muscular dystrophy, ex vivo gene transfer to correct mutations, and autologous implantation back into muscles of the patient.
Dr. Eric Hoffman (Children's National Medical Center) is funded by CDMRP for preclinical research on exon skipping in DMD using morpholino technology. With CDMRP support, he also has developed a mouse service core for testing therapeutics, is developing a detailed understanding of proteolytic pathways as therapeutic targets, and has initiated a high-throughput screening program for a variety of cell/molecular targets in DMD.
Dr. Kaime also described projects funded through the DoD Peer-Reviewed Medical Research Program (PRMP). Dr. Timothy Koh (University of Illinois at Chicago) has been supported by the PRMP for research on urokinase plasminogen activator and PAI-1, plasminogen activator inhibitor, two components of the coagulation system that he is linking to regeneration of injured muscle. Likewise, Dr. Kevin Campbell is supported for translational studies of muscle cell membrane repair through adeno-associated viral vectors (AAV) expressing the glycosyltransferase, LARGE. Additional work funded by PRMP in Dr. Campbell's lab is developing transgenic mouse models for study of the membrane repair protein, dysferlin.
A clinical trial supported by PMRP at the University of Pittsburgh is examining the efficacy and side effect profile of the combination of coenzyme Q10 and prednisone versus either drug alone.
Dr. Hesterlee asked whether details of CDMRP-supported projects would be made available on a web site. Dr. Kaime indicated that this information would be available shortly. Dr. Porter stated that one objective of the new Duchenne Research Collaborative International (DRCI) effort was to have the abstracts of all research grants that are funded in muscular dystrophy, whether by governmental or advocacy organizations, available on a single web site. Ms. Furlong confirmed that the DRCI effort has this as one of its objectives.Top
Dr. Hesterlee remarked that, from the patient advocacy group perspective, it was gratifying that the NIH was putting considerable resources and effort into supporting the MDCC and its work. As background, she noted that the MDA was founded in the early 1950s and currently supports research in over 40 different neuromuscular diseases, including the muscular dystrophies. MDA's budget for the current year was $40M, with approximately $17M in grants supporting muscular dystrophy research. The MDA also sponsors over 230 neuromuscular disease clinics across the United States. These MDA clinics function primarily in patient care, but Dr. Hesterlee commented that future plans are to try to elevate this program into a clinical research network.
Dr. Hesterlee related the MDA grant portfolio to the major components of the MDCC Action Plan, noting that she was reporting the prior year's figures since the MDA database was currently being updated and current figures were unavailable. A breakdown of MDA research by Action Plan component identified Disease Mechanisms (44%) and Therapy Development (45%) as the major elements. She pointed to a large increase in MDA support for pharmacological treatments, principally because of expenditures through the MDA Translational Research Advisory Committee (TRAC) program and emphasized the substantive diversity among the therapeutic development strategies receiving support. Dr. Katz and Dr. Hesterlee discussed the difficulty experienced by all funding agencies and organizations in the coding of research grants-particularly in assigning basic science research projects as either fundamental or disease-related research.
Dr. Hesterlee described the MDA's translational research program, first initiated in 2003, as a means of addressing the 'valley of death' between basic science and clinical trials. She noted that this is traditionally the area addressed by industry, but that industry was less interested in rare disorders (affecting under 250,000 people in the U.S. by NIH terms and less than 200,000 people by FDA terminology) such as muscular dystrophy, necessitating advocacy involvement to fill the gap. Like the other MDA programs, the research funded through the MDA TRAC is largely investigator-initiated, but the MDA staff have become much more involved with project solicitation, initiation, and management. Through the TRAC, the MDA has developed preclinical and clinical plans for addressing therapy development in the muscular dystrophies and uses these plans to guide MDA TRAC activities. She noted the clear need for infrastructure projects, but the difficulty in getting such projects funded, and noted that the MDA TRAC had established a special grant mechanism to support infrastructure (one example of MDA-funded infrastructure is Glen Morris' antibody resource). The MDA TRAC also has put a corporate grant category into place to directly fund companies involved in developing therapies for neuromuscular disease (e.g., a Phase IB trial for gene therapy in DMD). Dr. Hesterlee noted that MDA TRAC grants were all milestone-driven, with monitoring by a steering committee of outside experts. Data from two MDA-supported clinical trials in muscular dystrophy, PTC 124 and mini-dystrophin trials, are expected to be available shortly.
Dr. Hesterlee noted that the MDA was less involved in the Screening and Diagnosis and Living with Muscular Dystrophy components of the MDCC Action Plan. She remarked that it was important that the DoD was funding mouse screening infrastructure and felt that a corresponding muscular dystrophy dog screening facility also should receive support as much-needed therapy development infrastructure. A meeting participant asked what the obstacles were for implementation of a dog screening facility. Dr. Hesterlee replied that the dogs are expensive, have long gestational times, and that not many investigators have the resources and expertise to manage dogs and test therapeutics in this model. Dr. Joe Kornegay (University of North Carolina), an expert in the dog models of DMD, briefly summarized his experience with the dog models and the benefits to be gained versus the obstacles to use of these models. In response to a question from Mr. Perez, Dr. Kornegay noted that all dog models in current use were the consequence of naturally occurring mutations and that creation of transgenic dog models for muscular dystrophy would present huge challenges.
MDA has provided funds to defer the travel costs for subjects participating in clinical trials. Mr. Donovan Decker noted his prior participation in clinical trial for muscular dystrophy and asked whether there were mechanisms to defray the travel costs for patients participating in clinical studies and trials. Dr. Katz replied that travel support was available on a case-by-base basis for NIH-funded studies, usually dependent upon the difficulty in recruiting subjects for a specific study.Top
Ms. Furlong presented the activities of PPMD relative to the MDCC Action Plan, but first noted that the overall philosophy of the PPMD was that everything matters and every child matters-that everyone should think about the children and whether they are making decisions that improve lives and accelerate treatment. She compared data that an average 70-year old person lives for 25,500 days, while the average DMD patient diagnosed at 4 years of age has only 7,300 days left in his life.
Ms. Furlong emphasized the importance of collaborative efforts in addressing muscular dystrophy, including working through DRCI to create a global registry and international clinical trial network and in partnerships with FED, Nash-Avery, Charlie's Fund, Ryan's Hope, and Cure Duchenne to develop therapies. She described a grant with the Genetic Alliance, to develop a tool kit, metrics, and educational materials to ensure access to credible genetics services for patients and families.
To help reduce the diagnostic odyssey, PPMD has begun a genotyping campaign to address the substantial proportion of children in the U.S. who do not yet have the molecular diagnosis needed to determine clinical trial eligibility. The PPMD is collaborating with the CDC on a pilot outreach program in the State of Mississippi to learn how to best insure that there is a pathway forward (clinical care and a wide range of other services) for individuals after diagnosis. PPMD is also collaborating with the CDC on MD STARnet in the area of population surveillance. An issue that has arisen in these studies is the possible low frequency of DMD in African Americans-this is an important factor as if confirmed it could lead to the identification of disease modifier genes. PPMD is currently updating the tools they previously developed for patients, family members, and care providers.
PPMD has been working on a model for comprehensive patient care both at Cincinnati Children's Hospital and at Children's Hospital of Pennsylvania. The goal is to develop a new paradigm for care, since insurers often will not pay for a child to be seen by multiple sub-specialists.
Ms. Furlong noted that communication has been a central objective for PPMD and that the organization would soon hold the 14th annual conference, now with associated CME credit for physicians, and has recently conducted separate workshops on behavior and cardiac care.
In the area of the Therapy Development component of the MDCC Action Plan, PPMD is continuing to support development of the exon skipping strategy and toxicology studies for PTC 124. She described the PPMD Project Catalyst initiative and how this has led to funding of an NIH cooperative agreement to Dr. Lee Sweeney and PTC Therapeutics to pursue development of drugs for four specific targets in muscular dystrophy. PPMD is considering adding the cardiac SERCA1A target to its Project Catalyst program and has also been working with the NIH on resolving drug supply and formulation issues for a NIH-supported trial with the protease inhibitor, BBIC.
Ms. Furlong described an effort in collaboration with UPPMD to develop common data elements for national muscular dystrophy registries and to work toward formation of a global registry in DMD. Additional activities within DRCI are to develop appropriate outcome measures for upcoming clinical trials in DMD. Dr. Katz commented that Ms. Furlong should look into the NIH Roadmap Patient Reported Outcome Measures of Information Systems (PROMIS) activities in relationship to development of outcome measures for chronic diseases.
Mr. Perez raised a concern that, with the growth in support for muscular dystrophy, there is still substantial new resources being devoted to enterprise-registries, databases, networks, etc. Ms. Furlong indicated that she shared the frustration that resources were necessary for infrastructure and that progress in patient management and treatment was not faster. Dr. Katz commented that research and infrastructure has to be multifaceted, in large part because we don't know the best directions to pursue in order to obtain therapies. Mr. Decker, as a limb girdle muscular dystrophy patient who participated in a phase I gene therapy trial, emphasized the importance of patient participation in clinical studies, even when the early stage activities will not be of direct benefit to them.Top
Dr. Michelle Lloyd-Puryear first reviewed the HRSA mission, to facilitate the provision of resources and services for individuals and families throughout the U.S. with an emphasis on under-served and under-represented populations. HRSA funds a system of community health centers nationwide, the National Service Corps, and specific initiatives in physician and allied health professions training. HRSA Maternal and Child Health block grants support State public health infrastructure. Dr. Lloyd-Puryear commented that HRSA is on the other end of the translational spectrum from most MDCC agencies and organizations, ensuring that research is translated into everyday clinical and public health practice and that it affects everyday lives.
HRSA funding has supported establishment of infrastructure for services that individuals and families may need to take care of themselves or their children. Dr. Lloyd-Puryear noted that the HRSA activity potentially of most relevance to the MDCC is the development of specific technologies, and evaluation of the efficacy of technologies, for youth and newborn screening programs. She noted that she serves as Executive Secretary for the Advisory Committee on Heritable Disorders and Genetic Diseases of Newborns and Children to advise the Secretary on mortality or morbidity from heritable disorders in newborns and children.
Dr. Lloyd-Purview reviewed activities of the American College in Medical Genetics relative to muscular dystrophy. This group looked at newborn screening policies, and muscular dystrophy was one condition that they considered for inclusion on a uniform screening panel for newborns across the U.S. DMD was not initially selected for the screening panel, but policies are in place to review this status as management and therapy in the area improves, thereby improving the rationale for inclusion. She noted that the Advisory Committee on Heritable Disorders and Genetic Diseases of Newborns and Children has put mechanisms into place for individuals and groups to nominate conditions to the Committee for its review and recommendations. Dr. Katz asked what the key factors were in DMD not being accepted for the screening panel. Dr. Lloyd-Puryear answered that the issues were twofold-that a population-based screening test for the condition had to be in place and that a therapeutic needed to exist, although the Committee was softening the later requirement for genetic disorders.
In response to a question, Dr. Lloyd-Puryear described the genetic screening process, where over 4 million newborns are screened annually for a variety of conditions-via heel stick blood on filter paper for between eight and fifty conditions, depending upon the State. Other tests are done for metabolic disorders and a hearing test is done. She noted that this process was a screen, not a diagnosis, and screening positives still required confirmation in follow-up testing. Mr. Perez noted that FSHD patients have hearing loss at birth that should be detectable by State newborn testing. Ms. DiRosa commented that early testing could have considerable value in DMD, since many patients are not detected until they are much older (example given was 7 years of age) and that patient clinical signs were often discounted by teachers and physicians as within the normal range of development. Dr. Lloyd-Puryear agreed, noting that our health care system was not ideal and stressed the value of the newborn period and how a captive audience allowed universal conduct of screening tests.
Dr. Hesterlee asked if there would be an opportunity to reconsider adding DMD to the list of diseases and conditions on the screening panel. Dr. Lloyd-Puryear noted that the selection process had changed, but that additions to the screening panel would be considered. Dr. Kathy Mathews asked about the status of the CDC-funded newborn screening efforts for DMD. Ms. Costa commented that she expected to have information on those programs by the next MDCC meeting. Ms. Furlong raised the issues of false positives and negatives in newborn blood creatine kinase testing and of how that information would be handled is not an easily resolvable issue.Top
This portion of the MDCC meeting was designated for Committee members to discuss any gaps in planning for the muscular dystrophies. No formal presentations were scheduled.
Mr. Perez raised the issue of discrepancies in funding across the various types of muscular dystrophy. In particular, he acknowledged that the recent RFAs issued by the NIH and the MDA included FSHD, and that grants in the area were funded through the RFA, but he was concerned about the overall growth rate in the number of grants that the NIH has funded in FSHD. Dr. Katz answered that there was no funding cap at the NIH for muscular dystrophy and thus there was no head-to-head competition for support among the different diseases. FSHD then should not be regarded as in competition with other muscular dystrophies for research support. He noted that the impact of the RFA for EDMD, FSHD, and OPMD would not only be the grants that were just funded by the NIH and the MDA, but that the RFA had stimulated new applicants, who now would revise their applications and come back in for review as investigator-initiated applications. NIH program staff are working with these investigators, just as they are happy to facilitate applications in FSHD or any other muscular dystrophy. Dr. Katz also noted that if there was a concern with peer reviewers, that the NIH grant review system was viewed by many as the best way to help the NIH make funding decisions and that any concerned applicants could suggest reviewers for inclusion or exclusion in the evaluation of their applications.
Mr. Perez suggested that the review panel for muscular dystrophy grants (Skeletal Muscle and Exercise Physiology (SMEP)) had strength in DMD, but that reviewers were not well-versed in the other muscular dystrophies. Dr. Katz stated that anyone, from NIH institute directors to the lay public, has the opportunity to recommend people for NIH study sections. Mr. Perez asked if something could be done at the level of the MDCC to increase the number of grants funded in FSHD-having a mechanism to look across the different dystrophies, assess relative support levels, and make recommendations to the MDCC. There was a discussion of what those mechanisms might be-Dr. Katz stating that the RFA might result in a doubling of support for FSHD (official funding numbers not available until late 2007), while Mr. Perez noted that the absolute funding level would still be small relative to that of other types of muscular dystrophy and recommended that Wellstone Centers focus on specific types of muscular dystrophy. He suggested that an FSHD-oriented Wellstone Center would be a national resource for research, education, and treatment, focusing on what is not known and what information is need for progress in FSHD, not unlike the cancer centers that focus on specific types of that disease. Dr. Katz noted that the MDCC Action Plan had defined that mechanistic information was the key target at this time for FSHD and that the NIH would not predetermine the focus of the funded Wellstone Centers, but would look to peer review for the recommendations of relative merit of Wellstone applications.
Dr. Hesterlee suggested that a meeting that brought in a mix of investigators from both inside and outside the traditional FSHD field might be a way to bring new ideas and people to the table and focus on the problem in a very different way-she suggested that the MDA may be able to support a grant request for such a meeting. Mr. Perez and Dr. Katz discussed the issue of FSHD representation in the Wellstone Centers, with Mr. Perez concerned that a change in the composition of a Center that was up for renewal would eliminate FSHD presence in the program. Dr. Katz referred to Dr. Nuckolls' presentation describing the Wellstone collaborative projects that were just being initiated on FSHD themes. Dr. Porter also noted that NIH program staff were happy to advise investigators on the preparation of a Wellstone Center application that focuses upon FSHD or any muscular dystrophy.
Mr. Perez asked about continuing NIH support for registries in the muscular dystrophies, such as the NIAMS-/NINDS-funded FSHD and DM registry at the University of Rochester. Dr. Katz replied that, like other NIH-funded projects, registries are regularly evaluated by the NIH for continued funding and that the need and utility of the resource is an important consideration for continued support.Top
Dr. Hesterlee reviewed the newly formed DRCI effort-an initiative among U.S. and European groups to advance research in DMD. As research in DMD moves toward drug development and clinical testing, the required resources may it difficult for any one organization to see any one project through to use in patients. Thus, collaborations are becoming more the norm than the exception, especially among non-profit organizations that previously might have had adversarial relationships. As examples, she noted the active collaborations in spinal muscular atrophy, Friedreich's ataxia, and amyotrophic lateral sclerosis entered into by the MDA in recent years.
DRCI was initiated in January 2007 by the MDA, PPMD, the Association Francaise Contre les Myopathies (AFM), and the UPPMD, with the goal of increasing international collaboration, cooperation, and communication in DMD. An international approach was viewed as essential for a range of issues, including adequate patient recruitment for clinical trials and funding for preclinical and clinical stages of therapy development. Dr. Hesterlee noted that the objectives of DRCI would contribute to advancement of many components of the MDCC Action Plan in relationship to DMD, and that the DRCI model could be expanded for other forms of muscular dystrophy.
DRCI has put into place four collaborative projects. The first is a clearinghouse for research investments and resources. The MDCC meeting has made it apparent just how significant the available resources are, and has clearly established the need for one-stop-shopping for information on funded research and infrastructure to facilitate therapy development. The second DRCI project is a global patient registry, to facilitate clinical trials in DMD. Dr. Hesterlee noted that several registry projects were in existence and hoped that there could be an agreement on common data elements for cross-correlation among the various registries. The third DRCI project is a global clinical trial network-this was viewed as essential for very much the same reasons as the global registry; that this is a rare disease and clinical trials that test focused molecular therapeutics will need the ability to identify and recruit subjects with the appropriate genotypic/phenotypic profile. Dr. Katz noted that the challenges of multi-center international trials, including investigational review board (IRB) approvals, informed consent, safety monitoring, etc., would best be handled by way of the early approach advocated here by DRCI. There was a discussion of the difficulty in solving the issue of informed consent for use of the data in subsequent studies. Dr. Hesterlee discussed the concept of a 'hybrid IRB,' where a centralized IRB was in place that established communication with each local IRB involved in a study, in an attempt to minimize protocol review discrepancies and any time lags in protocol approval. Ms. Furlong noted that foundations are not restricted by IRBs and could facilitate data collection in ways not possible for industry or academic institutions. The last DRCI project is to establish a standing ethics committee, in part to develop ethical guidelines for relationships between industry and non-profit organizations.
Dr. Hesterlee also spoke briefly about the Translational Research in Europe-Assessment and Treatment of Neuromuscular Diseases (TREAT-NMD) initiative. She noted that this was a truly comprehensive clinical research network funded by the European Community. It sets up centralized infrastructure-for example, diagnostic and evaluation cores and a central data safety monitory board (DSMB) to ensure standards for collecting and storing data, for patient management, etc. Dr. Kate Bushby, who directs TREAT-NMD, was scheduled to present information on this effort at the following NIH Workshop on Translational Research in Muscular Dystrophy. Ms. Furlong pointed out that TREAT-NMD was included in the CDC care considerations process and that several collaborations were developing between U.S. and TREAT-NMD investigators. Meeting participants discussed expansion of TREAT-NMD collaborations to the remainder of the world, to take advantage of unique resources and patient populations.Top
Ms. Costa remarked that the key consideration in establishing a registry for a rare disorder, or any kind of registry or surveillance system for that matter, is the need for a clear purpose at the onset. From the CDC viewpoint, a central focus on population identification (demographics, short- and long-term outcomes, impact on patient and family, etc.) can be achieved through either a patient portal or a traditional surveillance mechanism. Another key registry consideration should be clinical management-necessitating access to the patient information directly from clinics and physicians. This function would be aided by the establishment of electronic medical records systems to automate passage of information into registries, although it was noted that numerous obstacles to implementation of such systems remain. The next key consideration in registry design is its utility for facilitation of clinical studies and trials. The need for molecular diagnosis for many of the putative therapies for DMD was discussed and how genotyping costs could be handled within the U.S.
The CDC has been examining the implementation of a DMD registry. Ms. Costa discussed a variety of issues related to the organization of such a registry, including its purpose and how it would relate to existing registries. Long-term issues such as registry housing, funding, and software viability represent important considerations that must be addressed at the onset. As a next step, the CDC plans to convene a steering committee to look at all issues connected with establishment of a DMD registry.
Ms. Carolyn Morrison asked whether CDC's experience with potentially contagious pathogens, pandemics, or bioterrorism issues had led to establishment of a protocol for international sharing of data that, in turn, could facilitate a global registry. Ms. Costa noted the potential for using such existing mechanisms and would look into their existence and feasibility for informing a DMD registry. Dr. Katz commented that international collaboration, even in the area of infectious disease, is a sensitive and complex issue that is not easily resolved. Dr. Lloyd-Puryear agreed that privacy issues represented a major hurdle.
Dr. Katz added that his thinking about the purposes of a registry included: (1) the purpose has to be clearly delineated at the onset, (2) established registries may be in existence for years and must ensure, as much as possible, that anticipated needs of the community are taken into account at the onset in the selected data elements, and (3) registries without repositories are acceptable, but that a related repository (blood, tissue) adds such an important dimension that it should be carefully considered at the time that the purpose decision is made. Dr. Hanson added the recommendation that the driving reason for sustaining a registry is not research, but rather the inherent responsibilities of public health assessment, assurance, and policy formulation. In response to a question about the relationship between CDC registry planning and the upcoming UPPMD meeting, Ms. Furlong noted the dual designs of registries, clinical versus patient, with their differing involvement of physicians and patients/families in actual data entry, and indicated that the upcoming UPPMD meeting was focused on a global patient-oriented registry, while the CDC focus was clinical.Top
Dr. Laurie Gutmann reviewed NINDS' efforts in development of data standards for clinical studies and trials. NINDS was confronted with the fact that each clinical study that was funded had unique data forms and elements and that investigators in separate studies frequently did not talk with each other. Care needed to be exercised in arriving at common data elements (CDEs), on one hand to reduce the costs of clinical trials and increase comparability of data across trials, but on the other hand to ensure that data collection took future needs into account.
Establishment of CDEs can reduce a clinical study's start-up time, speed the progress of the study and increase overall data quality, facilitate data sharing, and help educate new clinical investigators. To achieve these goals, the NINDS has set up a process, led by Dr. John Marler and Ms. Joanne Odenkirchen, to establish CDEs for neurological disorder studies. The group has established a dictionary, to ensure commonality in terminology, a manual of procedures, and a web site (http://www.nindscommondataelements.org). Dr. Gutmann showed how the NINDS group has sought to identify commonalities necessary for any type of data collection (e.g., demographics, medical history, inclusion, and exclusion criteria) and augments this core data set with additional elements as appropriate for specific diseases and conditions. Extensive community input is sought as core data sets are augmented for specific diseases. Dr. Gutmann indicated that the NINDS experience could aid a muscular dystrophy effort to achieve CDEs for clinical studies and trials.Top
Dr. Porter provided a brief introduction to the translational Workshop that was scheduled to immediately follow the annual MDCC meeting. The purpose of the Workshop is to provide an examination of ongoing efforts in therapy development for the muscular dystrophies, with an eye on improving the efficiency and effectiveness of these efforts. Specifically, the Workshop goals are to: (1) examine the current state of translational research in muscular dystrophy, (2) identify obstacles that may be blocking therapies in order to facilitate their rapid progression to the clinic, and (3) generate summary documents, including proceedings to be placed on the MDCC web site and a manuscript for peer-reviewed publication, to help guide future efforts in the field.
Dr. Porter reviewed the composition of the organizing committee, Drs. Cristina Csimma, Kathy Mathews, Jerry Mendell, Peter Wald, Lee Sweeney, and Sharon Hesterlee, and Mr. Perez, noting the inclusion of two MDCC members, and the basic organization of the Workshop. The Workshop included two keynote talks, to set the overall perspective, followed by working group presentations on therapeutic development processes, individual presentations on collaboration models, and working group presentations on the various strategies for therapy development in muscular dystrophy. Dr. Porter noted that a panel of external experts from industry and the FDA was recruited to advise participants on their perception of the ongoing therapy development activities in the muscular dystrophy field. A summary of the Workshop and the presenter PowerPoint presentations will be made available on the MDCC web site.Top
A participant asked about tracking efforts related to the MDCC Action Plan and was informed that the NIH will track activities and post progress on the MDCC web site.
Dr. Hesterlee asked how the NIH was using the MDCC Action Plan. Dr. Porter noted that the MDCC Action Plan was an important focal point for NIH activities in the muscular dystrophies. The NIH has already based three major initiatives to address Action Plan objectives-(1) the Nuclear Structure-Function Defects in Muscular Dystrophy RFA addresses mechanistic gaps in EDMD, FSHD, and OPMD, (2) the Translational Research in the Muscular Dystrophies program announcements address the need for preclinical therapy development support, and (3) the RFA to renew the Wellstone Centers contains programmatic revisions that have taken Action Plan objectives into account, including the emphasis on collaborative translational research projects and need for training of basic and clinical scientists to work in the muscular dystrophy field. MDCC Action Plan priorities also are a consideration in payment of applications in response to other NIH program announcements and for payment of some applications outside of the traditional NIH pay lines via the select pay process.
Mr. Perez asked if a more quantitative assessment could be put into place for the MDCC Action Plan; specifically noting what each NIH institute is supporting across the various types of muscular dystrophy. Dr. Katz noted that these data are released by each institute, typically within 3-4 months after the end of each fiscal year. Mr. Perez asked whether grant reporting could be related to the 79 objectives of the MDCC Action Plan. Dr. Katz noted the overlapping nature of the Action Plan objectives and the difficulty in relating each funded grant to individual objectives-instead the NIH has established a reporting system where individual grants are linked to subgroups of objectives within the major components of the Action Plan and is using this same system to collect information from MDCC member organizations.
Ms. Bozena Sporna read a statement on behalf of several DMD parents attending the MDCC meeting. She thanked committee members for their hard work on behalf of DMD and noted the importance of time in getting therapies developed for boys with the disease. Her statements put the work of the MDCC into the context of children with DMD who live with the disease 24 hours per day. Dr. Katz thanked Ms. Sporna and the group of parents that she represented, noting that the MDCC is acutely aware of the urgency experienced by individuals with muscular dystrophy. Ms. Leslie Guzman reinforced the notion that DMD parents were very willing to cooperate with data collection and therapy development efforts in the disease.
Dr. Katz thanked all participants for their input and candor and invited their participation in the NIH Workshop on Translational Research in Muscular Dystrophy that was scheduled to follow the MDCC meeting.
The MDCC meeting was adjourned at 3:25pm.
I certify that, to the best of my knowledge, the attachment and above minutes are accurate and complete.
Stephen I. Katz, MD, PhD
Chairperson, Muscular Dystrophy Coordinating Committee
Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Other Meeting Participants:
Last updated April 24, 2009