Investigating NMJ Defects in SMA Following Central and Peripheral SMN Restoration
brief summary
This is an observational study to investigate the improvement of NMJ defects in adult patients with SMA following treatment with Risdiplam. Eligible patients will have received treatment with daily oral Risdiplam after receiving approval through their commercial insurance or drug assistance program. All subjects will be evaluated at one visit. Eligible subjects must have been receiving risdiplam for at least 12 months.
detailed description
This is a proof of concept trial to investigate the impact of FDA approved therapy for adults with SMA on NMJ transmission. The study will enroll genetically confirmed adults with 5 q SMA treated with risdiplam for at least 12 months. Dosing will be weight- based as approved by the FDA (US Prescribing Information).
Assessments will include medical history, general physical and neurological examinations, vital signs, and the recording of adverse events. Diagnostic tests will include repetitive nerve stimulation (RNS), motor unit number estimation (MUNE), and decomposition EMG (dEMG). Further evaluations will utilize the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), the modified SMA Functional Rating Scale (SMAFRS), and the Fatigue Severity Scale (FSS). For ambulatory subjects, the assessment will include a six-minute walk test, while for non-ambulatory subjects, the Children's Hospital of Philadelphia Adult/Adolescent Test of Neuromuscular Disorders (CHOP INTEND) will be performed. Handheld dynamometry will be used to measure strength in bilateral shoulder abduction, elbow flexion, elbow extension, hip flexion, hip abduction, hip adduction, knee flexion, and knee extension.
The study aims to investigate the impact of Risdiplam on neuromuscular junction (NMJ) function by assessing changes in the percent decrement of the compound muscle action potential amplitude, as measured through 3 Hz repetitive nerve stimulation (RNS) of the spinal accessory nerve. These results will be compared to historical controls. Additionally, the study will evaluate the differences in strength, motor function, and electrophysiological test scores between groups, which will be stratified based on a 10% decrement cutoff. Further analysis will explore the association between these measures and percent decrement among ambulatory and non-ambulatory patients.