Beyond motor rescue: defining adequate SMN restoration in spinal muscular atrophy

• Text
• PDF

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.

Authors

Crystal Jing Jing Yeo