Evaluating the Effects of Nusinersen Treatment in Adults With Spinal Muscular Atrophy Using Axonal Excitability and...

The biological changes in motor neurons and motor axons that correlate with the clinical benefits of nusinersen, an antisense oligonucleotide, in spinal muscular atrophy (SMA) remain poorly understood. This study aimed to investigate changes in axonal excitability and motor unit number estimation (MUNE) parameters following a four-dose loading regimen of nusinersen in adult SMA patients.

Adult patients with SMA were assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Medical Research Council (MRC) scale at baseline and after nusinersen treatment. Axonal excitability studies and MScanFit MUNE were conducted in SMA patients before and after treatment. Baseline axonal excitability and MScanFit MUNE parameters in SMA patients were compared with those of a healthy control (HC) group.

Compared to the HC group (n = 10), SMA patients (n = 12) exhibited a significantly prolonged strength-duration time constant (SDTC), a higher resting current/voltage (I/V) slope, and prolonged refractoriness at 2.5 ms. However, no significant changes in axonal excitability parameters were observed following nusinersen treatment. Similarly, there were no significant changes in MUNE or in other parameters, including D50, compound muscle action potentials, and steps%. In contrast, a significant increase in HFMSE and MRC scores was observed after treatment (p < 0.01 and p = 0.01, respectively).

A prolongation of SDTC, likely due to its effect on sodium channel function, was observed in this study, consistent with existing literature. Despite improvements in motor function, no significant electrophysiological changes were detected in adult SMA patients.