Publication

Abstract : Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disorder characterized by progressive muscle weakness, atrophy, and respiratory failure due to selective degeneration of lower motor neurons arising from homozygous deletion of exon 7 (95%) or mutation in the SMN 1 gene (5%),with severity correlating with SMN2 copy number—from fatal Type1 to milder Type 4—affecting 1:6,000–10,000 births worldwide and burdening India with 1,500–2,000 annual cases amid diagnostic delays. Although the backup SMN2 gene compensates a bit for SMN deficiency, a critical C→T transition in exon 7 leads to exon skipping and production of a truncated, unstable and nonfunctional SMN protein. Recent advances in disease-modifying therapies-including antisense oligonucleotides, small-molecule splicing modifiers, and gene replacement-have significantly improved clinical outcomes; however, they do not restore endogenous SMN expression in all tissues and often require repeated administration. Despite these medications like Spinraza injections, Zolgensma gene therapy, Evrysdi pills that increase SMN protein, the condition still has got significant morbidity: Type 1 babies frequently die before the age of two, 60–95% develop scoliosis, which makes spinal injections uncomfortable and dangerous, and lifetime expenses for each patient surpass $2 million. What if we could edit the nucleotide base of SMN2(T6C) using ABE10 to make it emulate like SMN1 gene to restore stable functional SMN protein that would be the permanent cure for SMA. This cutting edge molecular tool “AI-based Adenine Base Editors” would facilitate an endogenous regulation, laying the groundwork for precision medicine in rare disease management.