SMA - Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is caused by the deficiency of a functional SMN1 gene that produces a protein in the body called Survival Motor Neuron (SMN) protein. Since SMN protein is critical to the survival and health of motor neurons, without this protein nerve cells may atrophy, shrink and eventually die, resulting in muscle weakness. The human genome carries a close paralog of SMN1, SMN2, that differs by a C to T transition in exon 7. This single-base difference causes preferential skipping of exon 7 in SMN2 mRNA, resulting in low expression of a functional SMN2 protein. Increased inclusion of SMN2 exon 7 would result in an increase in functional SMN protein that could rescue the SMA phenotype. Using RNA-modulating therapeutics, the authentic inclusion of exon 7 during SMN2 splicing can be enhanced.