Cumulative motor index in spinal muscular atrophy after gene therapy: baseline predicts maximal recovery.

OBJECTIVE

Higher compound muscle action potentials (CMAP) amplitudes are associated with motor milestones acquisitions in patients with symptomatic early onset spinal muscular atrophy (SMA) after gene therapy (GT). This study aimed to propose a predictive model for the evolution of CMAP amplitudes over 36 months in these patients.

METHODS

Nineteen SMA patients (mean age 8.5 months; 12 with two SMN2 copies, 7 with three) were prospectively assessed for motor scores and CMAP amplitudes (median, ulnar, fibular, tibial nerves). A cumulative motor index (CMI, sum of CMAP amplitudes) was calculated.

RESULTS

Post-GT, CMAP amplitudes and CMI increased significantly (p < 0.05) but plateaued at low pathological values after 24 months. The plateau occurred earlier and peaked lower in patients with two SMN2 copies, correlating also with a clinical motor plateau. In these patients, baseline CMI strongly predicted the maximal plateau value at 36 months (CMIM36=2.67×CMIM0+1.92; R2 = 0.97). Patients with three SMN2 copies plateaued at ∼10 mV, regardless of baseline CMI (R2 = 0.70).

CONCLUSION

The baseline CMI value emerged as a strong predictor of its maximal value after GT, along with the number of copies of SMN2.

SIGNIFICANCE: These results support the validation of CMI as a guide for optimal patient selection and therapeutic management.