Whole blood survival motor neuron protein levels correlate with severity of denervation in spinal muscular atrophy

Abstract

Introduction: We sought to determine whether survival motor neuron (SMN) protein blood levels correlate with denervation and SMN2 copies in spinal muscular atrophy (SMA).

Methods: Using a mixed-effect model, we tested associations between SMN levels, compound muscle action potential (CMAP), and SMN2 copies in a cohort of 74 patients with SMA. We analyzed a subset of 19 of these patients plus four additional patients who had been treated with received gene therapy to examine SMN trajectories early in life.

Results: Patients with SMA who had lower CMAP values had lower circulating SMN levels (P = .04). Survival motor neuron protein levels were different between patients with two and three SMN2 copies (P < .0001) and between symptomatic and presymptomatic patients (P < .0001), with the highest levels after birth and progressive decline over the first 3 years. Neither nusinersen nor gene therapy clearly altered SMN levels.

Discussion: These data provide evidence that whole blood SMN levels correlate with SMN2 copy number and severity of denervation.

Keywords: SMN protein levels; compound muscle action potential; denervation; spinal muscular atrophy; survival motor neuron.