Researcher develops, proves effectiveness of new drug for spinal muscular atrophy

"The strategy our lab is using to fight SMA is to 'repress the repressor,'" said Chris Lorson, a researcher in the Bond Life Sciences Center and professor in the MU Department of Veterinary Pathobiology. "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."

In individuals affected by SMA, the spinal motor neuron-1 (SMN1) gene is mutated and lacks the ability to process a key protein that helps muscle neurons function. Muscles in the lower extremities are usually affected first, followed by muscles in the upper extremities, including areas around the neck and spine.

Fortunately, humans have a nearly identical copy gene called SMN2. Lorson's drug targets that specific genetic sequence and allows proper "editing" of the SMN2 gene. The drug allows the SMN2 gene to bypass the defective gene and process the protein that helps the muscle neurons function.

Lorson's breakthrough therapeutic compound was patented in April. His research found that the earlier the treatment can be administered in mice with SMA, the better the outcome. In mice studies, the drug improved the survival rate by 500 to 700 percent, with a 90 percent improvement demonstrated in severe SMA cases, according to the study.

Although there is no cure for SMA currently, the National Institutes of Health (NIH) has listed SMA as the neurological disease closest to finding a cure, due in part to effective drugs like the one developed in Lorson's lab.

Lorson's study, "Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models," was published in September 2014 in the Journal of Human Molecular Genetics. Graduate student Erkan Osman was the lead author. The study was funded by a grant from the National Institutes of Health, a training grant and a fellowship from the Howard Hughes Medical Institute.