Opinion
Video
Considering New Duchenne Muscular Dystrophy Therapies: Excon Skipping and Gene Therapy
Author(s):
A panelist discusses how older DMD patients might benefit from newer genetic therapies including gene therapy and exon skipping, though eligibility depends on specific mutations and absence of pre-existing immunity to AAV vectors.
Clinical Brief: Genetic Therapy Eligibility in Advanced DMD
Main Discussion Topics
- Expansion of gene therapy eligibility criteria to include older, non-ambulatory patients
- Potential exclusion criteria for gene therapy, particularly mutations in exons 8-9
- Immunological considerations including pre-existing AAV antibodies
- Limited data on efficacy in older patients with advanced disease
Key Points for Physicians
- Accurate genetic diagnosis is essential for determining therapeutic eligibility
- Mutations in exon 8-9 region may increase risk of immune response to microdystrophin (~10-15% of patients)
- Pre-existing AAV antibodies (seropositivity) preclude gene therapy eligibility
- Recent expansion of approval allows treatment consideration even for 16-year-old patients
Notable Insights
The expert notes evolving exclusion criteria with initial exclusion of exons 1-19 mutations now narrowing to primarily exons 8-9, but cautions that other immunogenic regions may be identified as more patients are treated. Lack of published data on older patient outcomes represents a significant knowledge gap.
Clinical Significance
Despite expanded eligibility criteria for genetic therapies, careful patient selection remains critical, with mutation-specific considerations and immunological status determining appropriate candidates even in advanced disease stages.
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