Researchers at the University of Missouri are testing a new molecule that has proven to be highly effective in animal models exhibiting spinal muscular atrophy (SMA). The researchers hope their work will eventually result in new drugs for patients with SMA.
“Our team has been fine-tuning a potential therapeutic for SMA and what it does, ” said Chris Lorson, Ph.D., an investigator in the Bond Life Sciences Center and a professor of veterinary pathobiology in the University of Missouri College of Veterinary Medicine, in the July 25, 2016 news release. “It’s a type of molecule called an antisense oligonucleotide, or ASO, that essentially is synthetic string of nucleic acid that binds a specific sequence in the gene.”
According to the news release, “In individuals affected by SMA, the survival motor neuron-1 (SMN1) gene is mutated and lacks the ability to process a key protein that helps neurons function. Muscles that control walking or even lifting an arm often are profoundly affected as well as muscles important for breathing. Fortunately, humans have a nearly identical copy gene called SMN2, however, SMN2 normally only makes a small amount of the correct SMN protein. Lorson’s compound targets SMN2 and effectively ‘turns the volume up’ for SMN2, allowing it to make more of the correct SMN protein.”
“Our current treatment helps the body create a backup mechanism to combat the disease and extends survival in mice with SMA from just 13 days to a little over five months after only one injection at birth, ” Dr. Lorson said. “This treatment helps produce the right form of SMN, the one that was only produced at very low levels before.”
Dr. Lorson told OTW, “Our previous work on E1-targeting ASOs identified an initial candidate. In the current study, we sought to optimize the targeting sequence with the goal of further extending survival, reducing the SMA phenotype, and lowering the minimal dose that still elicited a phenotypic benefit.
“This works is still in the pre-clinical testing phase. Several ongoing clinical trials are showing promising results for ASOs (Biogen/Ionis), or gene therapy (AveXis) and hopefully these and other SMA-specific compounds and/or therapeutics are approved soon and a new wave of therapeutics will be available for a broad range of SMA patients.”
