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

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.