Spinal Muscular Atrophy: New Treatment and Challenge

Abstract

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder with an autosomal recessive inheritance and a spectrum of clinical presentations from the severe lethal infantile-onset SMA type I to the adult-onset SMA type IV. The disease is caused by mutations of the SMN1 gene leading to deficiencies of SMN protein. Additionally, the number of copies of SMN2 gene, a disease-modifier gene, which produces a small quantity of SMN protein, plays a major role in determining the clinical severity of the disease. Without diseasemodifying drugs, all patients have progressive weakness and deterioration of health over time. The effect on patients and their families is profound. This presentation will explain how the improved understandings of the molecular basis and natural history of SMA support the development of novel therapeutic strategies; as well as recognise the impact of the standardised care on outcomes. Therapeutic strategies in the pipeline, ranging from the modulation of SMN2 encoded transcripts to SMN1 gene replacement therapy, will be evaluated. This presentation will also share the local experience of the Hong Kong SMA treatment programme with nusinersen, which was started in 2018. The changes in motor outcome, health-related quality of life, and cerebrospinal fluid neurofilament level, pre-and-post-treatment, will be appraised. The way forward, which includes advancing the pre-symptomatic diagnosis and screening programme, establishing a transition of care programme, and setting up monitoring programme to determine the long-term impacts of the diseasemodifying treatments and further improvements in the supportive care, will be discussed.