Molecular Mechanisms and the Latest Advances in Precision Therapies for Spinal Muscular Atrophy

Abstract

Spinal Muscular Atrophy (SMA) is a serious autosomal recessive neuromuscular disorder. In the past few years, the rapid progresses of molecular genetics and precision medicine have greatly pushed the understanding of disease cause and the making of treatment methods for SMA. This review systematically sums up the newest advances in molecular mechanisms and accurate therapies of SMA during the time from 2024 to 2026. It highlights the regulatory roles of SMN1/SMN2 genes, non-coding RNAs, and epigenetic modifications, as well as pathophysiological alterations and disease-modifying factors induced by SMN protein deficiency. Furthermore, the clinic significances of SMN gene examination, biology markers, imaging examination, and newborn screening are all narrated in this paper. The effect and security of many accurate treatment methods, including antisense oligonucleotides, AAV-mediated gene substitution, small-molecule splicing modulators, and gene editing, are also assessed. At present, the problems that exist include the off-target effects brought by gene editing, relatively expensive treatment expenses, restricted acquisition channels, and not enough long-term follow-up observation data. Future directions include optimization of technical strategies, combination therapy, and translational application of biomarkers.