TDP-43 phase separation therapeutics for ALS-FTD

TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small molecules targeting phase separation properties could be therapeutic but the design principles are undefined.

{“hypothesis_matches”: [{“id”: “h-27bc0569”, “title”: “Liquid-Liquid Phase Separation Modifier Therapy”, “target_gene”: “G3BP1”, “target_pathway”: “Stress granule assembly / liquid-liquid phase separation”, “match_score”: 0.5, “composite_score”: 0.4141533204831823, “status”: “proposed”}, {“id”: “h-7693c291”, “title”: “RNA-Binding Competition Therapy for TDP-43 Cross-Seeding”, “target_gene”: “TARDBP”, “target_pathway”: “TDP-43 RNA-binding / liquid-liquid phase separation cross-seeding”, “match_score”: 0.3, “composite_score”: 0.3721712615349977, “status”: “proposed”}, {“id”: “h-4fabd9ce”, “title”: “Cryptic Exon Silencing Restoration”, “target_gene”: “TARDBP”, “target_pathway”: “TDP-43 RNA processing / phase separation”, “match_score”: 0.2, “composite_score”: 0.47657825606204984, “status”: “proposed”}, {“id”: “h-eea667a9”, “title”: “Cross-Seeding Prevention Strategy”, “target_gene”: “TARDBP”, “target_pathway”: “TDP-43 RNA processing / phase separation”, “match_score”: 0.2, “composite_score”: 0.4489384550402495, “status”: “proposed”}, {“id”: “h-7e846ceb”, “title”: “Glycine-Rich Domain Competitive Inhibition”, “target_gene”: “TARDBP”, “target_pathway”: “TDP-43 RNA processing / phase separation”, “match_score”: 0.2, “composite_score”: 0.4240845602343659, “status”: “proposed”}], “total_matching_hypotheses”: 5, “gap_tokens_sample”: [“ALS-FTD”, “TDP-43”, “als-ftd”, “becomes”, “design”, “liquid”, “liquid-liquid”, “molecules”, “pathological”, “phase”, “principles”, “properties”, “separation”, “small”, “targeting”], “updated_at”: “2026-04-06T08:21:05.714346+00:00”}