SMA – THERAPY: P.279 Efficacy and safety of nusinersen treated adult patients with spinal muscular atrophy (SMA) types 2-3-4

Abstract

Spinal muscular atrophy (SMA) is a genetic neurodegenerative disease, affecting the motor neurons in the spinal cord and leading to progressive muscular atrophy and weakness. The effect of nusinersen, a novel antisense oligonucleotide therapy in SMA, has primarily been studied in children up to 9 years old, with data on treatment of adult SMA patients still largely missing. The objective is to perform a detailed clinical and functional characterization and natural history analysis in 46 adult patients with SMA types 2-3-4 with (n=17) and without (n=29) intrathecal nusinersen treatment at our neuromuscular center at University Hospitals Leuven (Belgium). Outcome measures are collected prospectively over 14 months of treatment. These include the MRC sum score, 6-minute-walk-distance (6MWD), hand grip strength, Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), Activity Limitations Score (ActivLim), a quality of life questionnaire (SF-36) and a questionnaire for treatment-related side effects. Historical data is collected retrospectively of all 46 adult SMA patients from the patient files. The patients in the treatment group comprised of 10 males and 7 females aged 22 to 66 years, with a mean disease onset at 6.5 years of age (range 1-30y). One patient was classified as SMA2, 14 as SMA3 and two as SMA4. Seven patients were still ambulatory, with a mean 6MWD of 298.6 meters. Average age at loss of ambulation was 24.6 years (range 10-48y). Compared to the treated group, the untreated patient population was clinically more severely affected, with a significantly (p=0.006) larger proportion of SMA2 patients (n=13, with 15 SMA3 and 1 SMA4 patients) and only two patients (aged 34y and 41y) retaining ambulation. To conclude, we will present data on the efficacy and safety of nusinersen therapy in 17 patients with SMA types 2-3-4 over a treatment period of 14 months, as well as a natural history analysis in all 46 adult SMA patients.