Spinal muscular atrophy (SMA) is a genetic condition that is typically first diagnosed in infants and young children and is associated with high mortality in this population. SMA causes muscle weakness and progressive loss of movement. SMA is triggered by progressive deterioration in the nerve cells connecting the brain and spinal cord to the body’s muscles.
Current evidence shows that there is peripheral-tissue involvement in SMA. Patients have low levels of functional SMN, which is attributed to alternative splicing in SMN2, a gene closely-related to SMN1.
The decrease in the expression of SMN, a ubiquitously expressed protein involved in promoting snRNP assembly required for splicing, is thought responsible for the development of SMA. But evidence remains unclear about the molecular mechanisms involved in this SMN levels decrease.
At the moment there is no cure for this genetic disease, and potential treatments are still being researched. In order to improve the knowledge about SMA, molecular genetics research has been actively studying the role of the SMN restoring as a potential therapy.
Recently, researchers have been investigating the use of Antisense oligonucleotides (ASOs) to specifically alter splicing patterns of target pre-mRNAs, thus making a progressive advancement in this field of research. ASOS have been widely used in genetic disorders, and in the case of SMA they are able to synthesize the SMN gene, thorough mRNA bind, thus inactivating SMN.
In this regard, a team of researchers conducted a study entitled “The role of RNA splicing in the pathogenesis of spinal muscular atrophy and development of its therapeutics” that was recently published online in Europe PubMed Central.
The research team led by Sahashi Sobue from the Department of Neurology, Nagoya University Graduate School of Medicine, conducted a study where they identified an ASO that redirects SMN2 splicing. The team also examined the role of the splicing-modulating ASIS in animal SMA models, with promising results. These ASOS are currently being researched to be used as RNA-targeted therapeutics for SMA.
The team also found an association between spatial and temporal effects of therapeutics with the use of ASOS, thus providing encouraging knowledge new evidence for the SMA pathogenesis of SMA and its potential therapeutics.