Decision-making and challenges within the evolving treatment algorithm in spinal muscular atrophy: a clinical perspective.

The outlook for individuals with Spinal Muscular Atrophy (SMA) has transformed with the approval of three effective disease modifying therapies in the past seven years. This group of genetic diseases that cause progressive muscle weakness and present as a broad range of severity ­ from mild disease with near normal lifespan to severe with abbreviated lifespan and comorbidities ­ now have gene-based therapies that have shown (motor) functional gains, ameliorated comorbidities, and improved overall quality of life of patients and prolonged survival. With the rapid translation of early diagnostic paradigms through newborn screening and the acceleration of a therapeutic pipeline, uncertainties within clinical practice arise including the optimal time to treat, the changing clinical characteristics of the treated population, monitoring of disease progression and therapeutic response in the post-treatment era. In this article, we review the evidence base to address these challenges. The key factors that determine individual treatment choice and response are discussed. The changed clinical characteristics in treated children that need early identification and appropriate management are discussed in depth. A new classification system in keeping with the changed paradigm is provided. In these early times of the treatment era, the evidence from clinical trials and real world is combined to generate evidence base to guide management. The reader would be apprised of the recent therapeutic developments, their applications, and outcomes. Finally, the challenges to be expected along the uncharted path of prolonged lifespan are discussed and care guidelines provided.