Whole Blood SMN Protein Levels Correlate with Severity of Denervation in Spinal Muscular Atrophy.

INTRODUCTION We asked whether survival motor neuron protein (SMN) blood levels correlate with denervation and Survival of motor neuron 2 (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 SMA subjects. We analyzed a subset of 19 of these subjects plus 4 additional gene therapy treated subjects to examine SMN trajectories early in life. RESULTS SMA subjects with lower CMAP values had lower circulating SMN levels (P=0.04). SMN levels were different between subjects with 2 and 3 SMN2 copies (P<0.0001) and between symptomatic and pre-symptomatic subjects (P<0.0001), with the highest levels after birth and progressive decline over the first three years. Neither nusinersen nor gene therapy clearly altered SMN levels. DISCUSSION These data indicate that whole blood SMN levels correlate with SMN2 dosage and severity of denervation. This article is protected by copyright. All rights reserved.