Emerging Therapeutic Strategies for Spinal Muscular Atrophy: A Comprehensive Review

Abstract

Spinal Muscular Atrophy (SMA) is a genetic disorder that results in progressive muscle weakness due to the degeneration of motor neurons in both the spinal cord and brainstem. While there is currently no existing cure for the disease, drugs, and gene therapies have emerged as treatments to manage the severity of symptoms and improve patients’ outcomes. This literature review examines three major FDA-approved SMA treatments – Zolgensma®, risdiplam (Evrysdi®), and nusinersen (Spinraza®) – by analyzing results from key clinical trials. Zolgensma®, a gene replacement therapy, has resulted in increased event-free survival, acquisition of motor milestones, and maintenance of weight and respiratory function in patients. As the first oral SMA treatment, risdiplam approximately doubled SMN protein levels and improved motor function across various age groups. Nusinersen is another drug that allowed the achievement of WHO motor milestones and led to a reduced risk of mortality and permanent ventilation. Although there were adverse reactions and limitations with each treatment and its trials, the overall benefits such as increased motor function, respiratory status, and event-free survival were significant. This comprehensive review highlights the potential of these therapies to refine the treatment landscape for SMA. Further research monitoring long-term safety and exploring multiple approaches is warranted.