MDA Translational Research Program

Funded Projects
Updated 5-1-05

Supported Grants:

Corporate Grant:
“Phase I/II Study of Mini-Dystrophin Gene in AAV Vector”
PI: R. Jude Samulski, Ph.D., Asklepios Biopharmaceutical Inc.
$932,911 (yr1) $640,261(yr2)

The goal of this proposal is to carry out a double-blinded dose escalation Phase I/II gene therapy safety trial for Duchenne muscular dystrophy (DMD). A novel recombinant adeno-associated virus (AAV) vector carrying a functional mini-dystrophin gene will be utilized in these studies. Safety is the primary outcome measure of this trial. In addition to safety measurements, the protocol has been designed to obtain efficacy data. The long-term objective is to design, test develop and market a gene therapy approach for the treatment of DMD.

Corporate Grant:
“PTC 124 Treatment for Duchenne Muscular Dystrophy”
PI: Langdon Miller, M.D., PTC Therapeutics
$1,023,460 (yr1) $476,540(yr2)

Some patients have Duchenne muscular dystrophy (DMD) due to a nonsense mutation, or a premature stop codon, in their dystrophin gene. The nonsense mutation instructs the cellular protein production machinery to prematurely stop making dystrophin, resulting in a shortened, functionless dystrophin molecule that cannot maintain muscle structure and strength. PTC 124 is a new drug that may allow the cellular protein production machinery to ignore this abnormal stop signal, thereby restoring the production of full-length functional dystrophin. The ultimate aim of the proposed development program described in this grant application is to gain regulatory approval of PTC 124 as a treatment of patients with DMD resulting from a nonsense mutation in the dystrophin gene.

Infrastructure Grant:
“CMT North American Database”
PI: Michael Shy, M.D., Wayne State University.
$133,474 (yr1) $116,880 (yr2) $211,641 (yr3)

The CMT North American Database is created to provide a large number of well-studied patients with different types of CMT to be available for clinical trials and to answer questions such as whether certain medications exacerbate CMT, whether pregnancy exacerbates CMT or whether exercise helps CMT. In addition the Database will allow investigators to determine which mutations cause severe forms of CMT and to identify groups of patients who may be affected by novel forms of CMT. Patient confidentiality is strictly maintained in the database.

Infrastructure Grant:
“ALS/MDA C.A.R.E. Database”
PI: Robert G. Miller, M.D., California Pacific Medical Center
$146,959(yr1) $158,514(yr2) $160,848(yr3)

The ongoing ALS CARE program is a voluntary multicenter registry that has provided a unique source of information that may be used to improve the care of patients with ALS. The major focus of the new Web-based initiative will be to obtain long-term follow-up data and information about quality of life as well as survival. These data will be used to evaluate variations in patient care, adherence to standards of care and published practice parameters and also to help design clinical trials and epidemiological studies in ALS. An additional important focus of the Web-based ALS database will be to educate participating patients and visitors to the home page about ongoing clinical trials and clinical research studies, as well as to present an ongoing example of the role of the MDA/ALS division in the care of ALS patients nationwide.

Infrastructure Grant:
“A Monoclonal Antibody Resource for Genetic Neuromuscular Disease”
PI: Glenn Morris, Ph.D., North East Wales Institute
$117,437 (yr1) $99,429 (yr2) $104,579 (yr3)

Professor Morris’ biochemistry group has, over the past 20 years, built up a library of monoclonal antibodies for neuromuscular disease research, diagnosis and clinical trials. A collection of over 150 “exon-specific” antibodies against dystrophin is, and will continue to be, especially useful internationally in trials of potential therapies for Duchenne muscular dystrophy. Very popular antibodies have also been produced for research, diagnosis and drug evaluation in spinal muscular atrophy, Emery-Dreifuss muscular dystrophy and myotonic dystrophy. This project will ensure that these antibodies will continue to be available to researchers for the foreseeable future and will also add to and refine the library.
www.rjah.nhs.uk/cind/morrisge/mabs.htm

Wellstone Cooperative Centers for Muscular Dystrophy Research:
In 2003 MDA developed an agreement with the National Institutes of Health (NIH) to collaborate in providing supplemental funding to three cooperative research centers for muscular dystrophy research (later named “Wellstone” centers in honor of the late Senator Paul D. Wellstone). NIH offered up to $1 million per year for five years for each of the centers and MDA supplemented this amount with an award of up to $500,000 per year for three years for each center. See http://www.mda.org/news/030521partner.html for more information about this initiative.

Successful NIH center grantees were asked to focus their MDA supplemental support on the translational aspects of their planned research project. The following centers are supported through this effort:

“MDA Cooperative Center Supplement: Seattle, WA”
PI: Jeffrey Chamberlain, Ph.D., University of Washington
$499,968 (yr1) $499,968(yr2) $499,968(yr3)

MDA funding supplements four scientific projects and four cores:

Project 1: Preclinical studies and development of phase I clinical trial for gene transfer in DMD
Project 2: Test of AAV vectors in K9 DMD model
Project 3: Optimizing muscle-specific regulatory gene cassettes for human muscle gene therapy
Project 4: Molecular pathogenesis of myotonic dystrophy
Core A: Administrative Core
Core B: Viral Vector Core
Core C: Diagnostic and Genetic Counseling Core
Core D: Immunology Core

“MD Cooperative Center Supplement: Pittsburgh”
PI: Joseph Glorioso, Ph.D., University of Pittsburgh
$500,000 (yr1) $500,000 (yr2) $500,000 (yr3)

MDA funding supplements four scientific projects and three cores:

Project 1: Developing clinical outcomes for gene transfer
Project 2: Preclinical gene therapy in a large animal model of DMD
Project 3: Muscle stem cell-based therapies for cardiomyopathy and skeletal muscle degeneration
Project 4: Functional genomics studies of early myogenic differentiation
Core A: Administrative Core
Core C: Large-Animal Core

“MD Cooperative Center Supplement: Rochester”
PI: Richard Moxley, M.D., University of Rochester
$499,000 (yr1) $499,000 (yr2) $500,000 (yr3)

MDA funding supplements three scientific projects and three cores:

Project 1: Mouse muscle-bind model of myotonic dystrophy
Project 2: Effects of somatokine on myotonic dystrophy type 1
Project 3: Position effect and vascular adaptation in FSHD
Core A: Administrative Core
Core B: Repository Core
Core C: Imaging Core