Grant: Project Grant

Spinal muscular atrophy (SMA) is a serious inherited disease that causes progressive muscle weakness, breathing difficulties, and, in many cases, early death. New treatments that boost levels of a key protein called SMN have greatly improved survival. However, most of these medicines are delivered directly into the fluid around the spinal cord and mainly protect the nerves. Many people with SMA still develop significant problems in their breathing muscles, heart, and other organs throughout the body. These ongoing issues limit independence and quality of life. Our project aims to develop a safer, more effective "whole-body" treatment for SMA. We will study a genetic medicine called an antisense oligonucleotide-short pieces of synthetic DNA-like material that can correct how the SMN gene is processed. We attach this medicine to a small carrier molecule, called DG9, that is designed to help it reach muscles, the heart, and the brain after a simple injection under the skin. Using well-established SMA mouse models, we will test whether this treatment improves muscle strength, breathing, heart function, and survival, while carefully monitoring for side effects. We will also use advanced data analysis and machine learning to identify which measurements best predict long-term benefit, helping us design future clinical trials more efficiently. Finally, we will refine the DG9 carrier to achieve the best balance between effectiveness and safety. By targeting both the nervous system and the rest of the body, this research aims to create more complete and durable treatments that work alongside existing drugs to improve long-term outcomes for people living with SMA.