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

Autor: Alec J. Johnstone, Salomé Da Silva Duarte Lepez, Eric J. Eichelberger, Reid Garner, Rebekah Poxson, Rachel Schwartz, Victoria L. Stevens, Christiano R. R. Alves, Kathryn J. Swoboda, Phillip G. Zaworski, Ren Zhang, Vivian Yi
Rok vydání: 2019
Předmět:
survival motor neuron
0301 basic medicine
Male
medicine.medical_specialty
Physiology
animal diseases
Action Potentials
030105 genetics & heredity
SMN protein levels
Severity of Illness Index
Muscular Atrophy
Spinal
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Physiology (medical)
Internal medicine
Medicine
Humans
Muscle
Skeletal
Clinical Research Articles
spinal muscular atrophy
Whole blood
Denervation
Clinical Research Article
denervation
business.industry
Infant
Newborn
Infant
Spinal muscular atrophy
Motor neuron
medicine.disease
SMA
Survival of Motor Neuron 1 Protein
compound muscle action potential
nervous system diseases
Compound muscle action potential
medicine.anatomical_structure
Endocrinology
nervous system
Child
Preschool
Cohort
Nusinersen
Female
Neurology (clinical)
business
030217 neurology & neurosurgery
Zdroj: Muscle & Nerve
ISSN: 1097-4598
Popis: 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.
Databáze: OpenAIRE
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