SMN2 catalytic core for spinal muscular atrophy treatment
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 spinal muscular atrophy. Strategies to correct the splicing aberration in SMN2 are believed to hold promise for a cure for spinal muscular atrophy, 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 spinal muscular atrophy since it offers low cost synthesis, high target specificity, ease of manipulation and potential to cross the blood brain barrier.