Spinal muscular atrophy: Molecular genetics, Pathogenesis, and Therapeutic Approaches

Abstract

The mutation of ubiquitously expressed genes is regarded as one of the causes of many neurogenic disorders. Some of such disorders include Spinal muscular atrophy (SMA), Amyotrophic lateral sclerosis, Huntington’s disease, etc. Spinal muscular atrophy is the leading genetic cause of infant death caused by the disruption of Survival motor neuron 1(SMN1) by deletion, mutation, or conversion. In human two isoforms of SMN exists SMN1, which are the disease-causing gene, and its paralog SMN2 that are retained. No effective medical treatment was known until the discovery of this disease-causing gene. The molecular understanding of SMN gene regulation greatly contributes to the development of treatment options. In the past few decades, there has been an intriguing development in the treatment of SMA, including antisense oligonucleotide therapy (Nusinersen), gene therapy (Onasemnogene abeparvovec), and small-molecule pre-mRNA modifiers (Risdipalm). The range of current strategies to impede the pathological mechanism in neurodegeneration can be expanded by better understanding these new medications and gene-related therapies for SMA. Thus, we briefly discuss our understanding of SMA and the disease-causing genes and outline some important therapeutic strategies that have been developed.