Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series

This longitudinal cohort study aimed to determine whether circulating neurofilaments (NFs) can monitor response to molecular therapies in newborns with spinal muscular atrophy (SMA; NCT02831296). We applied a mixed-effect model to examine differences in serum NF levels among healthy control infants...

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Autores principales: Christiano R.R. Alves, Marco Petrillo, Rebecca Spellman, Reid Garner, Ren Zhang, Michael Kiefer, Sarah Simeone, Jihee Sohn, Eric J. Eichelberger, Emma Rodrigues, Elizabeth A. Arruda, Elise L. Townsend, Wildon Farwell, Kathryn J. Swoboda
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Publicado: Elsevier 2021
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spelling oai:doaj.org-article:db25a4904c724193bfc8efc310be89542021-11-20T05:06:45ZImplications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series2329-050110.1016/j.omtm.2021.10.011https://doaj.org/article/db25a4904c724193bfc8efc310be89542021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2329050121001686https://doaj.org/toc/2329-0501This longitudinal cohort study aimed to determine whether circulating neurofilaments (NFs) can monitor response to molecular therapies in newborns with spinal muscular atrophy (SMA; NCT02831296). We applied a mixed-effect model to examine differences in serum NF levels among healthy control infants (n = 13), untreated SMA infants (n = 68), and SMA infants who received the genetic therapies nusinersen and/or onasemnogene abeparvovec (n = 22). Increased NF levels were inversely associated with SMN2 copy number. SMA infants treated with either nusinersen or onasemnogene abeparvovec achieved important motor milestones not observed in the untreated cohort. NF levels declined more rapidly in the nusinersen cohort as compared with the untreated cohort. Unexpectedly, those receiving onasemnogene abeparvovec monotherapy showed a significant rise in NF levels regardless of SMN2 copy number. In contrast, symptomatic SMA infants who received nusinersen, followed by onasemnogene abeparvovec within a short interval after, did not show an elevation in NF levels. While NF cannot be used as the single marker to predict outcomes, the elevated NF levels observed with onasemnogene abeparvovec and its absence in infants treated first with nusinersen may indicate a protective effect of co-therapy during a critical period of vulnerability to acute denervation.Christiano R.R. AlvesMarco PetrilloRebecca SpellmanReid GarnerRen ZhangMichael KieferSarah SimeoneJihee SohnEric J. EichelbergerEmma RodriguesElizabeth A. ArrudaElise L. TownsendWildon FarwellKathryn J. SwobodaElsevierarticleNeuromuscular diseasesNeurogeneticsBiomarkersSMAGene TherapyGeneticsQH426-470CytologyQH573-671ENMolecular Therapy: Methods & Clinical Development, Vol 23, Iss , Pp 524-538 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neuromuscular diseases
Neurogenetics
Biomarkers
SMA
Gene Therapy
Genetics
QH426-470
Cytology
QH573-671
spellingShingle Neuromuscular diseases
Neurogenetics
Biomarkers
SMA
Gene Therapy
Genetics
QH426-470
Cytology
QH573-671
Christiano R.R. Alves
Marco Petrillo
Rebecca Spellman
Reid Garner
Ren Zhang
Michael Kiefer
Sarah Simeone
Jihee Sohn
Eric J. Eichelberger
Emma Rodrigues
Elizabeth A. Arruda
Elise L. Townsend
Wildon Farwell
Kathryn J. Swoboda
Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series
description This longitudinal cohort study aimed to determine whether circulating neurofilaments (NFs) can monitor response to molecular therapies in newborns with spinal muscular atrophy (SMA; NCT02831296). We applied a mixed-effect model to examine differences in serum NF levels among healthy control infants (n = 13), untreated SMA infants (n = 68), and SMA infants who received the genetic therapies nusinersen and/or onasemnogene abeparvovec (n = 22). Increased NF levels were inversely associated with SMN2 copy number. SMA infants treated with either nusinersen or onasemnogene abeparvovec achieved important motor milestones not observed in the untreated cohort. NF levels declined more rapidly in the nusinersen cohort as compared with the untreated cohort. Unexpectedly, those receiving onasemnogene abeparvovec monotherapy showed a significant rise in NF levels regardless of SMN2 copy number. In contrast, symptomatic SMA infants who received nusinersen, followed by onasemnogene abeparvovec within a short interval after, did not show an elevation in NF levels. While NF cannot be used as the single marker to predict outcomes, the elevated NF levels observed with onasemnogene abeparvovec and its absence in infants treated first with nusinersen may indicate a protective effect of co-therapy during a critical period of vulnerability to acute denervation.
format article
author Christiano R.R. Alves
Marco Petrillo
Rebecca Spellman
Reid Garner
Ren Zhang
Michael Kiefer
Sarah Simeone
Jihee Sohn
Eric J. Eichelberger
Emma Rodrigues
Elizabeth A. Arruda
Elise L. Townsend
Wildon Farwell
Kathryn J. Swoboda
author_facet Christiano R.R. Alves
Marco Petrillo
Rebecca Spellman
Reid Garner
Ren Zhang
Michael Kiefer
Sarah Simeone
Jihee Sohn
Eric J. Eichelberger
Emma Rodrigues
Elizabeth A. Arruda
Elise L. Townsend
Wildon Farwell
Kathryn J. Swoboda
author_sort Christiano R.R. Alves
title Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series
title_short Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series
title_full Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series
title_fullStr Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series
title_full_unstemmed Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series
title_sort implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: a case series
publisher Elsevier
publishDate 2021
url https://doaj.org/article/db25a4904c724193bfc8efc310be8954
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