Clinicogenetic characterization and response to disease-modifying therapies in spinal muscular atrophy: real-world experience from a reference center in Southern Brazil.

Objective: Spinal Muscular Atrophy linked to chromosome 5q (SMA) is an autosomal recessive neurodegenerative disease characterized by progressive proximal muscle atrophy and weakness. This study addresses the scarcity of research on novel disease-modifying therapies for SMA in Latin America by reporting a real-world experience in Southern Brazil.

Methodology: This is a single-center historical cohort that included all patients diagnosed with spinal muscular atrophy at a Regional Reference Service for rare diseases.

Results: Eighty-one patients were included, of whom 7 died during follow-up. Of the remaining 74 patients, 5.4 % were classified as pre-symptomatic, 24.3 % with SMA type 1, 28.4 % with type 2, 36.5 % with type 3, and 5.4 % with type 4. The mean follow-up time ranged from 1.8 years for pre-symptomatic cases to 8.7 years for SMA types 2 and 3. Approximately 42 % of these patients received specific disease-modifying therapy, of these, 96.8 % received Nusinersen, with 19.4 % transitioning to gene therapy using Onasemnogene Abeparvovec, and 6.4 % starting Risdiplam. Most patients with SMA type 1 were on disease-modifying treatment, whereas only slightly over a third of patients with type 2 and about 10 % of type 3 were receiving such treatments. Among treated patients, 80 % demonstrated improvement in motor performance during the follow-up, with a lesser therapeutic response being associated with late initiation of treatment and low motor function scores at baseline.

Conclusion: This real-world study reinforces the effectiveness of disease-modifying therapies for SMA in Brazil within the context of low- and middle-income countries, which is greater the earlier and the better the patient's functional status.