Treatment For Spinal Muscular Atrophy

Spinal muscular atrophy is an inherited disorder caused by homozygous deletions or variants in the SMN1 gene. As a consequence of absent or low levels of survival motor neuron 1 protein, the motor neurons in the spinal cord degenerate, resulting in atrophy of the voluntary muscles of the limbs and trunk. Treatments in this review include 1) Nusinersen which is a synthetic antisense oligonucleotide designed to bind to a specific sequence in exon 7 of the SMN2 transcript causing the inclusion of exon 7 in the SMN2 transcript, leading to the production of full-length functional survival motor neuron 2 protein, which is very similar to SMN1. 2) Onasemnogene abeparvovec-xioi which is intended as a one-time gene replacement therapy designed to deliver a functional copy of the SMN1 gene to motor neuron cells of patients with spinal muscular atrophy. Because motor neurons are nondividing cells, it is postulated that once the SMN1 gene is incorporated in the cells, it would be retained over time and potentially allow for long-term, sustained survival motor neuron protein expression. 3) Risdiplam which is a once-daily self-administered oral therapy. It is a selective SMN2 splicing modifier designed to bind with specificity to SMN2 pre-mRNA to modulate SMN2 pre-mRNA splicing towards the production of full-length SMN2 mRNA.