Sarah Knutson
Senior Director - Early Discovery Early Discovery ROME Therapeutics
Seminars
Thursday 4th June 2026
Targeting LINE‑1 Retrotransposon Activity to Address Neurodegeneration & Inflammation in ALS
11:00 am
- LINE‑1 retrotransposons can become aberrantly active under stress, contributing to genomic instability and neuroinflammation in ALS
- Selective LINE‑1 reverse transcriptase inhibitors suppress cytosolic LINE‑1 activity and blunt innate immune activation
- Preclinical models show neuroprotective effects, supporting motor neuron survival and reducing pathological signaling
- Translational considerations include biomarker development, CNS delivery, and differentiating selective inhibitors from earlier non‑specific approaches
Thursday 4th June 2026
Panel Discussion: Blending Modalities for Complex Neurodegeneration: What Will It Take to Treat ALS?
2:30 pm
- 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
