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.

SUBMITTER: Alves CRR 

PROVIDER: S-EPMC7496476 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature