Panel Discussion: Blending Modalities for Complex Neurodegeneration: What Will It Take to Treat ALS?
- How regulatory expectations differ across modalities (oral small molecules, ASOs, viral gene therapies, RNA medicines, cell therapies) and how developers can prepare for emerging FDA/EMA frameworks in ALS
- Which modalities are best suited for distinct ALS biological subtypes, including TDP-43 proteinopathy, C9orf72 repeat expansion, inflammatory/neuroimmune signatures, and mitochondrial/metabolic dysfunction
- Opportunities and challenges for combining modalities—for example coupling gene modulation with neuroprotective small molecules, pairing oligos with smallmolecule chaperones, or integrating metabolic stabilizers with anti-inflammatory approaches
- How modality mechanisms intersect (protein homeostasis, RNA regulation, axonal transport, synaptic resilience) and how cross-mechanistic synergy could inform trial design or biomarker development
- What is needed to run smarter, modality-agnostic clinical trials—harmonized biomarkers (NfL, speech, digital mobility), shared control arms, adaptive designs, and platform/basket approaches