• Center on Health Equity & Access
  • Clinical
  • Health Care Cost
  • Health Care Delivery
  • Insurance
  • Policy
  • Technology
  • Value-Based Care

Splicing Modifiers and Gene Therapy for SMA

Opinion
Video

Panelists discuss how splice modifiers work by enhancing protein production from the SMN2 gene, with risdiplam (Evrysdi) being an oral daily medication and nusinersen (Spinraza) being administered intrathecally quarterly, both showing similar safety and efficacy profiles.

Clinical Brief: Disease-Modifying Therapies for Spinal Muscular Atrophy (SMA)

Main Discussion Topics

  • Detailed description of splice modifiers (nusinersen and risdiplam) as key treatments for older patients with SMA
  • Mechanism and limitations of gene replacement therapy (onasemnogene abeparvovec [Zolgensma])
  • Administration considerations for different treatment options
  • Potential challenges and adverse events associated with gene therapy

Key Points for Physicians

  • Nusinersen requires intrathecal administration via lumbar puncture, with quarterly maintenance dosing.
  • Risdiplam is an oral daily medication now available in tablet form, improving adherence.
  • Gene therapy (onasemnogene abeparvovec) delivers a functional copy of SMN1 but is currently limited to patients younger than 2 years in the US.
  • Gene therapy carries risks including hepatic inflammation, cardiac events, and thrombocytopenia, requiring intensive monitoring.

Notable Insights

Patient preferences regarding treatment administration (daily oral medication vs quarterly intrathecal injection) may influence therapy selection, with some older patients preferring the less frequent dosing schedule of nusinersen despite its more invasive administration.

Clinical Significance

Selection of disease-modifying therapy for older patients with SMA currently involves choosing between nusinersen and risdiplam based on administration considerations, access to medical facilities, and patient preference, while gene therapy research continues for older populations.

Related Videos
5 experts are featured in this series
5 experts are featured in this series
4 experts are featured in this series.
4 experts are featured in this series.
1 expert is featured in this series.
Gordon Crofoot, MD, PA
Dr Brian Slomovitz
4 experts are featured in this series.
Related Content
© 2025 MJH Life Sciences
AJMC®
All rights reserved.