Funding outcome

Spinal muscular atrophy (SMA) is a severe illness that affects children's muscles, making it difficult for them to move, walk, and play like other kids. SMA is the most common genetic cause of death in infants worldwide. Most SMA patients do not survive more than a few years. Recently, the FDA has approved a few treatments for SMA, including small DNA-like molecules called antisense oligonucleotides (ASOs), gene replacement therapy, and small molecules. While these treatments are promising, they do not work well enough for everyone and often lose effectiveness after just a couple of years. Additionally, many children suffer from severe side effects, including immune responses, inflammation, painful injections into the spine, and off-target effects, which can be life-threatening. Our research focuses on a new approach using a tiny helper called DG9. DG9 acts like a special delivery truck, carrying the ASO medicine directly to the parts of the body that need it most. We already demonstrated the superior efficacy of DG9-delivered ASOs compared to the FDA-approved ASO in a severe mouse model of SMA, including improved survival and muscle function (Aslesh et al. JCI Insight. 2023). It requires an injection under the skin only. We are developing different versions of DG9 to find the best one for delivering this important medicine to help kids with SMA. The effects and safety of these DG9 variants will be tested in a severe mouse model of SMA to ensure they work effectively and safely. This new type of treatment could greatly improve the lives of children with SMA by helping them gain better muscle control, move more easily, and enjoy a healthier, more active life. Our goal is to create a therapy that works longer and has fewer side effects, providing a more reliable and safer option for children with SMA Our hope is that one day, SMA will no longer be a life-limiting condition, but a manageable one, thanks to advancements in medical research and therapy development.