Splicing Modifiers and Gene Therapy for SMA

EP: 1.Describing SMA Progression Over Time

EP: 2.Unmet Needs of Older Patients Living With SMA

EP: 3.Examining the Importance of Early Treatment for SMA

EP: 4.Key Functional Milestones Affected by Disease Progression

EP: 5.The Importance of Supportive Care for Patients Living With SMA

EP: 6.Introduction to Therapies Used to Treat SMA

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EP: 7.Splicing Modifiers and Gene Therapy for SMA

EP: 8.Key Clinical Considerations for the Management of SMA

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.