Abstract Details

Title Serial Compound Muscle Action Potential to Assess Improvement Following Gene Modifying and Replacement Therapies in Spinal Muscular Atrophy

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 9-007

Objective

This study aims to investigate the utility of serial compound muscle action potential (CMAP) amplitudes in early-onset spinal muscular atrophy (SMA) before and after onasemnogene abeparvovec-xioi gene replacement therapy.

Background

Despite major therapeutic breakthroughs for SMA, including gene replacement therapy, there remains an unmet need for objective, longitudinal biomarkers to evaluate disease severity and treatment response in newborns identified through state-mandated screening programs. Functional tests (CHOP-INTEND) are not validated beyond early infancy and tend to plateau over time, limiting their utility. Serial CMAP assessments may provide a quantifiable electrophysiologic measure of ongoing motor-unit maturation.

Design/Methods This current longitudinal-cohort study included 17 infants with SMA (two-SMN2 copies, n=9; three-SMN2 copies, n=8; girls, n=8). Assessments were conducted at baseline and two follow-ups after gene therapy. Evaluations included right median (recorded from abductor pollicis brevis, APB), ulnar (abductor digiti minimi, ADM), and fibular (tibialis anterior, TA) CMAP amplitudes (mV), along with the CHOP-INTEND.

Results CHOP-INTEND scores plateaued at 6-months follow-up, the CMAP scores continue to rise. Right median-APB [Median 3.3 mV (IQR: 2.6–4.0) to 5.8 mV (IQR: 3.4–6.8) and 6.9 mV (IQR: 6.1–9.5), respectively P<0.001] and fibular-TA amplitudes increased similarly [median 2.6 mV (IQR: 2.1–3.2) to 4.4 mV (IQR: 2.9–5.3) and 5.5 mV (IQR: 4.7–6.3), respectively P<0.001] amplitudes showed significant longitudinal gains. Right ADM amplitudes also rose over time [median 3.9 mV (IQR: 2.0–6.7) to 6.8 mV (IQR: 3.7–8.0) and 7.5 mV (IQR: 6.2–9.0), respectively P=0.008]. The increase in CMAP amplitudes were steeper among infants with two-SMN2 copies.

Conclusions Serial median-APB and fibular-TA amplitudes are sensitive biomarkers able to assess motor-unit maturation following gene-replacement-therapy in SMA patients beyond infancy, while CHOP-INTEND scores plateaued at six months of life. Further analysis, correlating serial CMAP data with highest motor milestone achieved and its value in guiding treating teams to start combinatorial therapies (i.e. risdiplam, onasemnogene-abeparvovecxioi, nusinersen) are being explored.

Authors/Disclosures
Bahadir M. Samur, MD PRESENTER	Dr. Samur has nothing to disclose.
Sneha Sadhu	Ms. Sadhu has nothing to disclose.
Zhulin He (Emory University)	No disclosure on file
Sumit Verma, MD (Emory Children's Center)	Dr. Verma has nothing to disclose.

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