Stimulating endogenous muscle stem cells to counter muscle atrophy
Grant Award Details
Grant Type:
Grant Number:
DISC2-10604
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$2,198,687
Status:
Closed
Progress Reports
Reporting Period:
Year 2 – 6-month NCE
Grant Application Details
Application Title:
Stimulating endogenous muscle stem cells to counter muscle atrophy
Public Abstract:
Research Objective
Intramuscular delivery of two repurposed FDA approved drugs will activate resident muscle stem cells. This therapeutic strategy will augment regeneration and restore strength to atrophied muscles.
Impact
Currently effective treatments are lacking for localized muscle atrophy due to nerve injury (eg., Carpal Tunnel Syndrome) or immobilization after trauma or surgery (eg., hip or knee replacement).
Major Proposed Activities
Intramuscular delivery of two repurposed FDA approved drugs will activate resident muscle stem cells. This therapeutic strategy will augment regeneration and restore strength to atrophied muscles.
Impact
Currently effective treatments are lacking for localized muscle atrophy due to nerve injury (eg., Carpal Tunnel Syndrome) or immobilization after trauma or surgery (eg., hip or knee replacement).
Major Proposed Activities
- To establish the optimal dose of the formulation based on the stem cell proliferative response and safety profile
- To establish biomarkers for efficacy of the formulation in muscle regeneration
- To establish the non-invasive biometrics for functional outcome of intramuscular treatment
- To assess long-term effects of drug treatment on aged muscle regeneration
- To address regenerative response of the drug treatment in aged denervation muscle atrophy model
- To evaluate the efficacy of the drug treatment on human muscle xenograft
Statement of Benefit to California:
Our therapeutic strategy stands to revolutionize treatment of muscle atrophy. Muscle wasting is a highly debilitating condition that impacts quality of life and productivity with an incidence that increases with aging. In particular, Carpal Tunnel Syndrome, a work related injury, impedes use of the hand with economic consequences. As California is the most populous state, with an ever-increasing elderly population, it will benefit from strategies that increase mobility of this demographic.
Publications
- Biomaterials (2021): Biophysical matrix cues from the regenerating niche direct muscle stem cell fate in engineered microenvironments. (PubMed: 34224984)
- Nat Methods (2023): Hardwiring tissue-specific AAV transduction in mice through engineered receptor expression. (PubMed: 37291262)
- Science (2021): Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength. (PubMed: 33303683)
- Nat Commun (2022): Primary cilia on muscle stem cells are critical to maintain regenerative capacity and are lost during aging. (PubMed: 35301320)
- Cell Stem Cell (2020): Tissue Stem Cells: Architects of Their Niches. (PubMed: 33007238)