Funding outcome

Duchenne muscular dystrophy (DMD) is a genetic disease affecting 1/5000 boys worldwide causing progressive, body-wide muscle weakness and breakdown. Patients are usually wheelchair-bound by age 12, require assistance breathing by their late teens, and typically only live to their mid-late twenties as DMD eventually affects the heart, leading to DMD-related heart failure and death. While no cure currently exists for DMD, a recent form of treatment called antisense oligonucleotide (AON) therapy has shown great promise, and four AONs are currently available to help treat patients. AONs are small DNA-like molecules that 'skip over' disease-causing mutations in the gene associated with DMD, restoring partial function and reducing the burden of disease. Unfortunately, current AONs do not work well in the heart, which is a critical target given that heart failure is the main cause of death in DMD. Additionally, all currently approved AONs target a similar region in the DMD gene, and so many patients still do not have access to this life-changing therapy. To address these issues, we aim to design molecules that: 1) Demonstrate high therapeutic benefit in the heart and 2) Target regions in the DMD gene not currently treated with AONs. To accomplish this, we have developed novel proteins that attach to AONs and improve the their uptake into the heart, and we have targeted them to a currently untreated cluster of DMD-causing mutations. We expect this research to lead to eventual clinical trials, where they can impart direct clinical benefit to DMD patients suffering from DMD and DMD-related heart failure.