The Evolution of Disease-Modifying Therapies in Spinal Muscular Atrophy from Palliative to Curative Intent: a Clinical Pharmacy Narrative Review

Abstract

Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder, which is characterized by a progressive degeneration of motor neurons attributed to lack of survival motor neuron (SMN) protein. Historically, SMA management was limited to palliative and supportive therapy to enhance the quality of life and minimize the occurrence of complications; however, development of disease-modifying therapies (DMTs) has revolutionized the landscape of therapy for SMA and involves the use of therapies that target the underlying genetic defect. This review aims to provide an extensive insight in the pathophysiology of SMA and clinical manifestations as well as history of treatment strategies with focus on the mechanism, clinical efficacy and limitations of the 3 approved DMTs nusinersen, onasemnogene abeparvovec and risdiplam based on different molecular approaches for increasing SMN protein levels. Furthermore, the need for early diagnosis and in particular newborn screening is developed as a major factor in determining the success of treatment. The growing role of clinical pharmacists in the choice of therapy, monitoring and pharmacoeconomic issues are discussed in this article. Even with these advancements, challenges remain, such as the high cost of therapy, safety concerns over the long term, variability in the response of the patient, and the requirement for combination therapy or medicines that do not depend on SMN, thus highlighting the need for ongoing research and multidisciplinary methods of care.