The Genetics of Mental Retardation

Abstract

<h3>Objective</h3> To determine changes in motor and respiratory function after treatment with nusinersen in adults with spinal muscular atrophy (SMA) during the first two years of commercial availability in the USA. <h3>Methods</h3> Data were collected prospectively on adult (age &gt;17 years at treatment initiation) SMA participants in the Pediatric Neuromuscular Clinical Research (PNCR) Network. Baseline assessments of SMA outcomes including the Expanded Hammersmith Functional Rating Scale (HFMSE), Revised Upper Limb Module (RULM), and 6-Minute Walk Test (6MWT) occurred &lt;5 months before treatment, and post-treatment assessments were made up to 24 months after nusinersen initation. Patient-reported experiences, safety laboratory tests and adverse events were monitored. The mean annual rate of change over time was determined for outcome measures using linear mixed effects models. <h3>Results</h3> Forty-two adult SMA participants (mean age: 34 years, range 17-66) receiving nusinersen for a mean of 12.5 months (range 3-24 months) were assessed. Several motor and respiratory measures showed improvement distinct from the progressive decline typically seen in untreated adults. Participants also reported qualitative improvements including muscle strength, stamina, breathing and bulbar related outcomes. All participants tolerated nusinersen with normal surveillance labs and no significant adverse events. <h3>Conclusions</h3> Trends of improvement emerged in functional motor, patient-reported, and respiratory measures, suggesting nusinersen may be efficacious in adults with SMA. Larger well-controlled studies and additional outcome measures are needed to firmly establish the efficacy of nusinersen in adults with SMA. <h3>Classification of Evidence</h3> This study provides Class IV evidence regarding nusinersen tolerability and efficacy based on reported side effects and pulmonary and physical therapy assessments in an adult SMA cohort.