DWORF Gene Therapy for DMD
Abstract
Systemic adeno-associated virus (AAV) micro-dystrophin gene therapy is currently being tested in Duchenne muscular dystrophy (DMD) patients. Since the size of micro-dystrophin is only one-third of full-length dystrophin, functional improvement from micro-dystrophin therapy is limited. Novel creative strategies are in urgent need to enhance micro-dystrophin therapy. Dwarf open reading frame (DWORF) is a newly discovered micro-peptide. DWORF enhances muscle contractility by increasing sarco/endoplasmic reticulum calcium ATPase (SERCA) activity. DWORF has never been explored for DMD therapy. However, SERCA therapy has been shown to ameliorate muscle disease in mouse DMD models. We reason DWORF therapy can also treat DMD and will test this hypothesis in this project. Since DWORF is small enough to fit into an AAV. micro-dystrophin vector, we will also test AAV.micro-dystrophin/DWORF combined therapy in this project. We expect AAV.micro-dystrophin/DWORF to greatly outperform AAV.micro-dystrophin therapy. We expect to finish mouse studies in 2 years. If our hypothesis is confirmed, we will apply new funding to test AAV.micro-dystrophin/DWORF therapy in the canine DMD model.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210808
Entities
People
- Dongsheng Duan
Organizations
- Curators of the University of Missouri
- United States Army