Current Treatment Process and Challenges for Spinal Muscular Atrophy (SMA)

Abstract

Spinal muscular atrophy (SMA) presents as a pediatric neuromuscular disorder resulting from mutations in the survival motor neuron 1(SMN1) gene, with an incidence of approximately 10-13 per 100,000 live births. This condition manifests primarily through muscle weakness and atrophy, particularly affecting the proximal limb muscles. A homozygous deletion of exon 7 in the SMN1 gene is the most common genetic mutation in SMA and serves as a sensitive diagnostic marker. This article comprehensively explores various aspects of SMA, including its types, diagnostic methods, and management strategies. Pulmonary care, gastrointestinal (GI) management, nutritional supplementation, orthopedic spinal care, and physiotherapy play crucial roles in delaying disease progression. Current pharmacological treatments for SMA are diverse and evolving. Notable among them is Zolgensma (formerly AVXS-101 or Onasemnogene abeparvovec), a gene replacement therapy utilizing an adeno-associated virus vector to boost functional SMN protein levels. Sodium vanadate, a phosphatase inhibitor, and risdiplam (RO703406) are agents that modulate SMN2 splicing to augment the production of functional SMN protein. Riluzole acts as a neuroprotective agent by preventing SMN deficiency, while reldesemtive (CK-2127107) is under development as a muscle-enhancing therapy to ameliorate skeletal muscle function during fatigue. While pharmacological therapies for SMA are advancing, a holistic approach involving comprehensive multidisciplinary care, encompassing pulmonary support, proper nutritional supplementation, and adept orthopedic management, significantly contributes to the effective management of SMA.