Project 452647

Spinal muscular atrophy (SMA) is a devastating genetic disease of children. It is the most common genetic cause of infant death in Canada and worldwide. Type 1 SMA is the most frequent and severe form of the disease. Most children with type 1 SMA live only a few years and die from complications with breathing. The disease affects their nerves throughout their body, leaving them unable to move muscles. SMA is caused by an error in a specific gene, blocking their ability to produce an essential protein for survival. However, humans have a nearly identical copy of this gene that can produce about 10% of the essential protein. This small amount of the protein helps children with SMA to survive long enough to be born. The biological miracle is, however, short-lived because 10% of the essential protein is not enough to stay healthy. To produce the essential protein properly, only a small error in DNA needs to be corrected. Our new technology is a DNA-like molecule that acts like a molecular bandage to cover up a part of the gene. Covering that part allows the essential protein to be produced properly and in amounts large enough for good health. We have designed and tested several types of these molecular bandages. Some could restore almost normal levels of the essential protein in human cells. They could also improve SMA symptoms in mice. Two key challenges still must be solved. First, what is the most efficient way to get these molecular bandages into the cells of children with SMA? Second, could they have harmful effects in children? Our goal for this research is to develop a safer and more effective molecular bandage. One day we hope that the error in the gene of children with SMA can be covered up and their SMA can be treated effectively.