Beyond motor rescue: defining adequate SMN restoration in spinal muscular atrophy.
4 affiliations
- 1National Neuroscience Institute, Singapore, Singapore.
- 2Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
- 3Duke-National University of Singapore Medical School, Singapore, Singapore.
- 4Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
Spinal muscular atrophy (SMA) is characterized by motor neuron degeneration due to deficiency in the survival of motor neuron (SMN) protein. Disease-modifying therapies have transformed outcomes in SMA, while also revealing an increasingly complex spectrum of residual disease biology. In this issue of the JCI, Tapken, Rahmel-Stein, and colleagues demonstrated cell-specific SMN expression and persistent alterations in peripheral immune cell populations in nusinersen- or risdiplam-treated adults with SMA. Their findings extend the question of selective vulnerability beyond motor neurons and raise an increasingly important therapeutic question: What constitutes adequate SMN restoration? This Commentary considers how cell type, developmental timing, SMN requirement, and downstream response may shape treatment-modified SMA, with implications for systemic and CNS-directed therapies.
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BibTeX
@article{yeo2026beyond,
title = {{Beyond motor rescue: defining adequate SMN restoration in spinal muscular atrophy.}},
author = {Crystal Jing Jing Yeo},
journal = {The Journal of clinical investigation},
year = {2026},
month = nov,
doi = {10.1172/jci211991},
url = {https://europepmc.org/article/MED/42969230},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beyond motor rescue: defining adequate SMN restoration in spinal muscular atrophy.
AU - Crystal Jing Jing Yeo
PY - 2026
DA - 2026/11/02
JO - The Journal of clinical investigation
DO - 10.1172/jci211991
UR - https://europepmc.org/article/MED/42969230
AB - Spinal muscular atrophy (SMA) is characterized by motor neuron degeneration due to deficiency in the survival of motor neuron (SMN) protein. Disease-modifying therapies have transformed outcomes in SMA, while also revealing an increasingly complex spectrum of residual disease biology. In this issue of the JCI, Tapken, Rahmel-Stein, and colleagues demonstrated cell-specific SMN expression and persistent alterations in peripheral immune cell populations in nusinersen- or risdiplam-treated adults with SMA. Their findings extend the question of selective vulnerability beyond motor neurons and raise an increasingly important therapeutic question: What constitutes adequate SMN restoration? This Commentary considers how cell type, developmental timing, SMN requirement, and downstream response may shape treatment-modified SMA, with implications for systemic and CNS-directed therapies.
SN - 0021-9738
SN - 1558-8238
ER -