Can Dystrophin-Replacement Therapies Improve Cognitive Function in DMD? Development of Strategies to Maximize Effectiveness and Avoid Detrimental Effects
Abstract
This project explores the potential windows for optimal use of dystrophin replacement strategies on neurodevelopment outcomes. The prolonged developmental process of myelination provides a therapeutic window of opportunity, but important unanswered questions remain. It remains unclear if postnatal dystrophin replacement would restore appropriate white matter development, and whether a critical window for therapeutic intervention exists. And, given the complexity of dystrophin expression in the brain, it may be that dystrophin replacement interfere with developmental trajectories that are regulated by endogenous dystrophins that are still present. The smaller dystrophin isoforms, which predominate in the postnatal brain, frequently remain expressed in DMD as their expression is driven by internal promoters that lie downstream of the more common DMD mutation hotspots. We are currently working to establish the cellular, temporal, and isoform requirements for potential dystrophin-replacing therapies, as well as for the capacity of dystrophin-replacement strategies to correct or disrupt brain developmental trajectories.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1190975
Entities
People
- Holly Colognato
Organizations
- State University of New York