Spinal muscular atrophy (SMA) is a neurodegenerative disorder that affects the control of muscle movement and is a leading genetic cause of infant mortality. SMA is divided into four subtypes based on disease severity and the age at which it manifests. In humans, there are two nearly identical copies of the
Survival Motor Neuron (SMN) gene,
SMN1 and
SMN2. Loss of
SMN1 in conjunction with skipping of
SMN2 exon 7 in pre-mRNA splicing—which results in a truncated, unstable SMN—leads to SMA. Strategies to correct the splicing aberration in
SMN2 are believed to hold promise for a cure for SMA, and have included screening many small compounds as well as the use of short antisense oligonucleotides (ASO). To date, however, no small compounds or ASO have been identified that can correct the
SMN2 splicing defect. As part of an ongoing research program in SMA, ISU researchers have now identified a novel short antisense oligonucleotide that corrects the aberrant splicing in
SMN2. This ASO may have utility as a potential treatment for SMA since it offers low cost synthesis, high target specificity, ease of manipulation and potential to cross the blood brain barrier.