Improving Micro-Dystrophin Efficacy in Older DMD Muscle Using Adjunct Therapies
Abstract
The goal of this project is to address a great unmet medical need by identifying small molecule drugs that can reverse the disease features of skeletal muscle in older Duchenne muscular dystrophy (DMD) patients. To accomplish this, we will evaluate two compounds that have shown the ability to remodel the muscles of older dystrophic mice by reducing muscle fibrosis and restarting muscle regeneration. Using a severe mouse model of DMD, these muscle remodeling therapeutics will be tested as monotherapies to benefit disease-ridden muscle representative of older DMD patients. This strategy will then be tested as a pre-treatment for micro-dystrophin gene therapy in order to improve the delivery and rescue effect of this emerging DMD therapeutic strategy in older patients. The impact of combining glucocorticoid treatments with these remodeling therapeutics and gene therapy will also be assessed, using both daily and intermittent glucocorticoid dosing methodologies. Information obtained from this research potentially will have immediate and impactful implications for the development of treatment strategies for older DMD patients, serving as both a way to reduce disease burden in muscles and to improve the effectiveness of gene therapy. Because this study is repurposing two clinical stage compounds as remodeling therapeutics, one of which is Food and Drug Administration approved, the findings of this project can lead to immediate implementation of these treatment strategies in the clinic.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211070
Entities
People
- David Hammers
Organizations
- United States Army
- University of Florida