TY - JOUR
T1 - Longitudinal prospective cohort study to assess peripheral motor function with extensive electrophysiological techniques in patients with Spinal Muscular Atrophy (SMA)
T2 - the SMA Motor Map protocol
AU - Ros, Leandra A.A.
AU - Goedee, H. Stephan
AU - Franssen, Hessel
AU - Asselman, Fay Lynn
AU - Bartels, Bart
AU - Cuppen, Inge
AU - van Eijk, Ruben P.A.
AU - Sleutjes, Boudewijn T.H.M.
AU - van der Pol, W. Ludo
AU - Wadman, Renske I.
N1 - Funding Information:
The study is supported by a grant from the non-profit organizations Stichting Spieren voor Spieren and Prinses Beatrix Spierfonds (combined grant W.OS18-01). The funder did not have any role in the design of the study, collection, analysis, and/or interpretation of the data. The investigators have full access to the data and have the right to publish this data separate and apart from any sponsor.
Funding Information:
This study is supported by the Dutch patient organization for neuromuscular diseases ( http://www.spierziekten.nl ). The patient organization has no role in the design, conduct or analysis of this study.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4/24
Y1 - 2023/4/24
N2 - Background: Hereditary spinal muscular atrophy (SMA) is a motor neuron disorder with a wide range in severity in children and adults. Two therapies that alter splicing of the Survival Motor Neuron 2 (SMN2) gene, i.e. nusinersen and risdiplam, improve motor function in SMA, but treatment effects vary. Experimental studies indicate that motor unit dysfunction encompasses multiple features, including abnormal function of the motor neuron, axon, neuromuscular junction and muscle fibres. The relative contributions of dysfunction of different parts of the motor unit to the clinical phenotype are unknown. Predictive biomarkers for clinical efficacy are currently lacking. The goals of this project are to study the association of electrophysiological abnormalities of the peripheral motor system in relation to 1) SMA clinical phenotypes and 2) treatment response in patients treated with SMN2-splicing modifiers (nusinersen or risdiplam). Methods: We designed an investigator-initiated, monocentre, longitudinal cohort study using electrophysiological techniques (‘the SMA Motor Map’) in Dutch children (≥ 12 years) and adults with SMA types 1–4. The protocol includes the compound muscle action potential scan, nerve excitability testing and repetitive nerve stimulation test, executed unilaterally at the median nerve. Part one cross-sectionally assesses the association of electrophysiological abnormalities in relation to SMA clinical phenotypes in treatment-naïve patients. Part two investigates the predictive value of electrophysiological changes at two-months treatment for a positive clinical motor response after one-year treatment with SMN2-splicing modifiers. We will include 100 patients in each part of the study. Discussion: This study will provide important information on the pathophysiology of the peripheral motor system of treatment-naïve patients with SMA through electrophysiological techniques. More importantly, the longitudinal analysis in patients on SMN2-splicing modifying therapies (i.e. nusinersen and risdiplam) intents to develop non-invasive electrophysiological biomarkers for treatment response in order to improve (individualized) treatment decisions. Trial registration: NL72562.041.20 (registered at https://www.toetsingonline.nl. 26–03-2020).
AB - Background: Hereditary spinal muscular atrophy (SMA) is a motor neuron disorder with a wide range in severity in children and adults. Two therapies that alter splicing of the Survival Motor Neuron 2 (SMN2) gene, i.e. nusinersen and risdiplam, improve motor function in SMA, but treatment effects vary. Experimental studies indicate that motor unit dysfunction encompasses multiple features, including abnormal function of the motor neuron, axon, neuromuscular junction and muscle fibres. The relative contributions of dysfunction of different parts of the motor unit to the clinical phenotype are unknown. Predictive biomarkers for clinical efficacy are currently lacking. The goals of this project are to study the association of electrophysiological abnormalities of the peripheral motor system in relation to 1) SMA clinical phenotypes and 2) treatment response in patients treated with SMN2-splicing modifiers (nusinersen or risdiplam). Methods: We designed an investigator-initiated, monocentre, longitudinal cohort study using electrophysiological techniques (‘the SMA Motor Map’) in Dutch children (≥ 12 years) and adults with SMA types 1–4. The protocol includes the compound muscle action potential scan, nerve excitability testing and repetitive nerve stimulation test, executed unilaterally at the median nerve. Part one cross-sectionally assesses the association of electrophysiological abnormalities in relation to SMA clinical phenotypes in treatment-naïve patients. Part two investigates the predictive value of electrophysiological changes at two-months treatment for a positive clinical motor response after one-year treatment with SMN2-splicing modifiers. We will include 100 patients in each part of the study. Discussion: This study will provide important information on the pathophysiology of the peripheral motor system of treatment-naïve patients with SMA through electrophysiological techniques. More importantly, the longitudinal analysis in patients on SMN2-splicing modifying therapies (i.e. nusinersen and risdiplam) intents to develop non-invasive electrophysiological biomarkers for treatment response in order to improve (individualized) treatment decisions. Trial registration: NL72562.041.20 (registered at https://www.toetsingonline.nl. 26–03-2020).
KW - Electrophysiological techniques
KW - Motor unit
KW - Nusinersen
KW - Risdiplam
KW - Spinal muscular atrophy
UR - http://www.scopus.com/inward/record.url?scp=85153687000&partnerID=8YFLogxK
U2 - 10.1186/s12883-023-03207-5
DO - 10.1186/s12883-023-03207-5
M3 - Article
C2 - 37095427
SN - 1471-2377
VL - 23
JO - BMC Neurology
JF - BMC Neurology
IS - 1
M1 - 164
ER -