Grant: Project Grant

Duchenne muscular dystrophy (DMD) is a severe genetic disease causing progressive muscle loss, leading to heart and respiratory failure. While gene and exon-skipping therapies offer hope, they struggle with limited delivery to muscles, immune reactions, and narrow patient applicability. Our research aims to expand and improve exon-skipping therapy, which helps restore a functional dystrophin protein in patients. By developing multi-exon skipping strategies, we aim to treat up to 55% of DMD patients, significantly increasing the number of individuals who could benefit while enhancing the functionality of truncated dystrophin. To enhance effectiveness in skeletal, heart, and respiratory muscles, we are optimizing DG9-PMO, a peptide-conjugated therapy that dramatically improves drug uptake, particularly in the heart and diaphragm-the organs most critical for survival. Building on our previous work that led to viltolarsen, the first FDA-approved exon-skipping drug, we will refine AON cocktails to improve stability, reduce complexity, and increase clinical feasibility. By addressing body-wide complications, especially in cardiac and respiratory muscles, this research could significantly extend and improve the lives of individuals with DMD while paving the way for future treatments in other neuromuscular diseases.