P225 Longitudinal changes in compound muscle action potential and their association with motor function in infantile-onset SMA children in ENDEAR/SHINE

Compound muscle action potential (CMAP) is a non-invasive, and simple-to-perform electrophysiological technique that can be used to provide physiologic information about motor units. Understanding the longitudinal changes of CMAP and their association with motor function outcomes in children with Spinal Muscular Atrophy (SMA) can help evaluate CMAP as a potential biomarker for therapeutic effects in SMA. Our analysis included 105 participants with infantile-onset SMA who initiated nusinersen in ENDEAR or long-term extension study SHINE (27 Aug 2019 datacut). The mean (standard deviation [SD]) of ulnar and peroneal CMAP amplitude at the time of first nusinersen dose (baseline) were 0.20 (0.18) and 0.35 (0.30) mV, respectively. CMAP amplitudes were significantly correlated with age at first dose and other measures of disease severity at baseline, including disease duration and motor function as measured by CHOP-INTEND (p-values from Spearman correlations <0.05). Both ulnar and peroneal amplitude increased significantly after nusinersen treatment initiation. The mean (SD) changes from baseline for ulnar and peroneal amplitudes were 0.26 (0.36) and 0.65 (0.75) mV at Day 394, and 0.49 (0.67) and 1.17 (1.22) mV at Day 818, respectively. Increases were greater for participants who were younger vs. older at first dose. Changes in CMAP amplitudes were moderately correlated with changes in CHOP-INTEND scores at most study visits, suggesting that physiological changes in motor units correspond with observed clinical outcomes after nusinersen treatment initiation. Correlations between changes in CMAP and CHOP-INTEND at Day 394 were 0.45 (p<0.01) and 0.28 (p=0.03) for ulnar and peroneal amplitude, respectively; the corresponding correlations were 0.45 (p<0.01) and 0.40 (p<0.01) at Day 818. The role of CMAP as a potential biomarker for reaching developmental milestones in infantile-onset SMA, such as achieving independent sitting, will be further examined. Compound muscle action potential (CMAP) is a non-invasive, and simple-to-perform electrophysiological technique that can be used to provide physiologic information about motor units. Understanding the longitudinal changes of CMAP and their association with motor function outcomes in children with Spinal Muscular Atrophy (SMA) can help evaluate CMAP as a potential biomarker for therapeutic effects in SMA. Our analysis included 105 participants with infantile-onset SMA who initiated nusinersen in ENDEAR or long-term extension study SHINE (27 Aug 2019 datacut). The mean (standard deviation [SD]) of ulnar and peroneal CMAP amplitude at the time of first nusinersen dose (baseline) were 0.20 (0.18) and 0.35 (0.30) mV, respectively. CMAP amplitudes were significantly correlated with age at first dose and other measures of disease severity at baseline, including disease duration and motor function as measured by CHOP-INTEND (p-values from Spearman correlations <0.05). Both ulnar and peroneal amplitude increased significantly after nusinersen treatment initiation. The mean (SD) changes from baseline for ulnar and peroneal amplitudes were 0.26 (0.36) and 0.65 (0.75) mV at Day 394, and 0.49 (0.67) and 1.17 (1.22) mV at Day 818, respectively. Increases were greater for participants who were younger vs. older at first dose. Changes in CMAP amplitudes were moderately correlated with changes in CHOP-INTEND scores at most study visits, suggesting that physiological changes in motor units correspond with observed clinical outcomes after nusinersen treatment initiation. Correlations between changes in CMAP and CHOP-INTEND at Day 394 were 0.45 (p<0.01) and 0.28 (p=0.03) for ulnar and peroneal amplitude, respectively; the corresponding correlations were 0.45 (p<0.01) and 0.40 (p<0.01) at Day 818. The role of CMAP as a potential biomarker for reaching developmental milestones in infantile-onset SMA, such as achieving independent sitting, will be further examined.