139P Treatment effects on ambulation loss in Spinal Muscular Atrophy Type III: insights from the Italian ISMAC registry

• Published in: Neuromuscular disorders : NMD 2024-10, Vol.43, p.104441, Article 104441.37
• Main Authors: Coratti, G., D'Amico, A., Sansone, V., Masson, R., Maggi, L., Mongini, T., Pegoraro, E., Pini, A., Vacchiano, V., Coccia, M., Filosto, M., Ticci, C., D'Errico, E., Nigro, V., Bruno, C., Messina, S., Pera, M., Pane, M., Mercuri, E.
• Format: Article
• Language: English
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.046

Spinal muscular atrophy (SMA) Type III is characterized by the loss of the SMN1 gene, resulting in progressive neuron degeneration. While initially ambulatory, patients may later face gait impairments, fatigue, and the risk of ambulation loss (LOA). This study investigates the variability of LOA and its correlation with treatments in a nationwide cohort of SMA Type III cases. Retrospective data from 28 Italian centers, representing the national segment of the ISMAC registry, were utilized. The analysis involved 429 individuals with Type III SMA. Initially, individual variables such as sex, SMN2 copy number, and SMA III subtype (IIIA and IIIB) were analyzed independently of treatment effects. Subsequently, treatment effects were incorporated, and interactions between variables were explored. Initial analysis revealed that individuals with higher SMN2 copy numbers had a lower risk of LOA, with a 57% lower risk for those with 4+ copies compared to 2 copies. Similarly, SMA IIIB individuals had a 78% lower risk of LOA compared to SMA IIIA. The second phase of analysis revealed that treatment status significantly influenced LOA risk, with treated individuals experiencing a 96% lower risk of LOA compared to untreated individuals. Subgroup analyses by SMA subtype and SMN2 copy number further revealed substantial associations. Treated SMA IIIA individuals had a 91% lower risk of LOA compared to untreated counterparts, while treated SMA IIIB individuals had an 88% lower risk. Moreover, higher SMN2 copy numbers were associated with a reduced risk of LOA among treated individuals. Those with 3SMN2 copies had an 85% lower risk, and those with 4+SMN2 copies had a 93% lower risk compared to untreated counterparts. These findings underscore the potential benefits of treatment in delaying ambulation loss in SMA Type III patients and highlight the importance of incorporating treatment effects into prognostic models for improved patient management.