Spinal muscular atrophy is a disease characterized by a short lifespan and progressive, debilitating symptoms. New research on mice, however, suggests that scientists may in the early stages of developing a new treatment that could eventually extend survival rates in children with SMA.
A new study entitled “Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models” published in September issue of Journal of Human Molecular Genetics reports a new morpholino-based drug that improves Spinal Muscular Atrophy in mice.
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused a genetic mutation in the Smn1 gene (short for spinal motor neuron-1), and currently does not have a cure. The lack of SMN1 protein leads to the death of motor neurons and consequently, muscle atrophy. In humans, there is a second gene called Smn2, but it produces low levels of functional protein due to a mechanism called alternative splicing. In this study, the researchers at the University of Missouri designed a strategy to overcome the alternative splicing in Smn2 gene and thus increase the expression of SMN protein. They used Morpholino-based antisense oligonucleotides to achieve this. When injected into a mouse model of severe SMA, the SMN protein expression was re-established, which resulted in extension of the survival rate. The results were even more pronounced in the intermediate SMA mouse model, where a 700% survival rate was achieved.
Chris Lorson, a researcher in the Bond Life Sciences Center and professor in the MU Department of Veterinary Pathobiology commented, “The strategy our lab is using to fight SMA is to ‘repress the repressor. It’s a lot like reading a book, but in this case, the final chapter of the book—or the final exon of the genetic sequence—is omitted. The exciting part is that the important chapter is still there—and can be tricked into being read correctly, if you know how. The new SMA therapeutic compound, an antisense oligonucleotide, repairs expression of the gene affected by the disease.”