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.
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.
Authors: Maren Freigang; Claudia D Wurster; Tim Hagenacker; Benjamin Stolte; Markus Weiler; Christoph Kamm; Olivia Schreiber-Katz; Alma Osmanovic; Susanne Petri; Alexander Kowski; Thomas Meyer; Jan C Koch; Isabell Cordts; Marcus Deschauer; Paul Lingor; Elisa Aust; Daniel Petzold; Albert C Ludolph; Björn Falkenburger; Andreas Hermann; René Günther Journal: Ann Clin Transl Neurol Date: 2021-03-31 Impact factor: 4.511
Authors: Eric J Eichelberger; Christiano R R Alves; Ren Zhang; Marco Petrillo; Patrick Cullen; Wildon Farwell; Jessica A Hurt; John F Staropoli; Kathryn J Swoboda Journal: Ann Clin Transl Neurol Date: 2021-05-15 Impact factor: 4.511