Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3 – A Prospective Observational Study

作者：Maggie Christine Walter, Stephan Wenninger, Simone Thiele, Julia M. Stauber, Miriam Hiebeler, Eva Greckl, Kristina Ståhl, Astrid Pechmann, Hanns Lochmüller, Janbernd Kirschner, Benedikt G. H. Schoser · 发表于：Journal of Neuromuscular Diseases · 年份：2019 · DOI：10.3233/jnd-190416 · 被引用次数：221 · 研究领域：Neurogenetic and Muscular Disorders Research、Amyotrophic Lateral Sclerosis Research、Spinal Dysraphism and Malformations

OBJECTIVE: Spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease caused by loss of the SMN1 gene. Based on randomized clinical trials in children with SMA type 1 and 2, Nusinersen has been approved as the first treatment for all types of SMA, including adults with SMA type 3. METHODS: We evaluated the safety and treatment effects of Nusinersen in longstanding adult 5q-SMA type 3. Patients were treated with intrathecal loading doses at day 1, 14, 28 and 63, followed by maintenance dose every four months up to 300 days. We monitored the patients within SMArtCARE, a prospective open-label outcome study for disease progression, side effects and treatment efficacy, encompassing clinical examination including MRC sum score, vital capacity in sitting position (VC, VC % pred.), ALS Functional Rating Scale (ALS-FRS), 6-Minute-Walk-Test (6MWT), Revised Upper Limb Module (RULM), and Hammersmith Functional Rating Scale (HFMSE). We also measured biomarkers in the spinal fluid (phosphorylated neurofilament heavy chain pNFH, neuron-specific enolase NSE, proteins, ß-Amyloid 1-40, ß-Amyloid 1-42, tau and phospho-tau) and creatine kinase (CK). Assessments were performed at baseline, day 63 (V4), day 180 (V5) and day 300 (V6). For statistical analysis, we compared baseline to V4, V5 and V6, using the paired sample t-test. When there were significant differences, we added cohen's d and effect size r for evaluation of clinical meaningfulness. RESULTS: 19 patients...