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 andSMN2copies in spinal muscular atrophy (SMA). Methods Using a mixed-effect model, we tested associations between SMN levels, compound muscle action potential (CMAP), andSMN2copies 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 threeSMN2copies (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 withSMN2copy number and severity of denervation.