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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Neuromuscular diseases Neurogenetics Biomarkers SMA Gene Therapy Genetics QH426-470 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/db25a4904c724193bfc8efc310be8954
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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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Implications of circulating neurofilamentsfor spinal muscular atrophytreatment early in life: A case series

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