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

Molecular Therapy: Methods & Clinical Development

Jihee Sohn¹  Rebecca Spellman²  Marco Petrillo³  Emma Rodrigues³  Elise L. Townsend⁴  Kathryn J. Swoboda⁴  Sarah Simeone⁴  Reid Garner⁴  Ren Zhang⁴  Wildon Farwell⁴  Christiano R.R. Alves⁴  Eric J. Eichelberger⁴  Elizabeth A. Arruda⁴  Michael Kiefer⁴ 

[1] Department of Physical Therapy, School of Health and Rehabilitation Sciences, MGH Institute of Health Professions, Boston, MA, USA;Takeda Pharmaceuticals, Lexington, MA, USA;Biogen, Cambridge, MA, USA;Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA;

关键词: Neuromuscular diseases;    Neurogenetics;    Biomarkers;    SMA;    Gene Therapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown