Project Details
Description
Abstract
Duchenne muscular dystrophy (DMD) is a devastating and universally fatal X-linked recessive disease of
progressive striated muscle deterioration. DMD boys have severe skeletal muscle wasting early in life and they
are typically wheelchair bound by age 10-12. DMD is fatal by the late teens to mid-twenties due to cardiac muscle
and respiratory muscle failure. These grim realities underscore the tremendous urgency to discover and
implement new approaches and therapies that could impact disease progression and outcomes in DMD.
Significance of this proposal to the NIH is tremendous. There is no cure for DMD, or any effective clinical
treatment that can halt or reverse the disease. This application derives outstanding health significance and
impact by focusing on first-in-class synthetic membrane stabilizers that directly target the primary physiological
defect in DMD: severe muscle membrane instability. Membrane stabilizers confer marked protection to
dystrophic cardiac muscle, however, until now, dystrophic skeletal muscles were not significantly protected,
tempering enthusiasm in the DMD field for this class of therapy. Now, for the first time to our knowledge, we find
that pharmacodynamically optimized membrane stabilizers have a dramatic protective effect in dystrophic limb
skeletal muscles in vivo. This potential therapeutic breakthrough has great significance to the NIH as a new
viable approach to treat dystrophic striated muscles. The overarching hypothesis directing this proposal is that
mechanistically guided structure-function analysis of synthetic block copolymers will illuminate new fundamental
insights into the cellular basis of how membrane stabilization protect muscles. These mechanistically guided
studies have great potential impact as they serve the required foundation in seeking the ultimate goal of effective
long-term protection to dystrophic striated muscles in vivo.
Status | Finished |
---|---|
Effective start/end date | 5/1/18 → 4/30/23 |
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $466,335.00
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $461,671.00
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $452,345.00
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $465,840.00
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: $466,335.00
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