Molecules that specifically sequester or neutralize C9orf72 arginine-rich dipeptide repeat proteins (DPRs) could prevent their disruption of normal TDP-43 phase separation, addressing a major upstream cause of TDP-43 pathology in C9orf72-ALS/FTD.
Debate provenance: derived from debate `sess_sda-2026-04-01-gap-006` on question: 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.. Consensus signal: clinical_trialist, domain_expert, medicinal_chemist, skeptic, synthesizer, theorist discussed the mechanism terms ALS/FTD, Agents, C9orf72, DPR, Neutralizing, TDP. Novelty signal: skeptic-discussed-with-qualified-concession.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
C9orf72["C9orf72"] -->|produces pathologi| DPR_proteins["DPR_proteins"]
C9orf72_1["C9orf72"] -->|risk factor for| ALS_FTD["ALS/FTD"]
C9orf72_DPR_neutralizing_["C9orf72 DPR neutralizing agents"] -->|prevents| TDP_43_phase_separation_d["TDP-43 phase separation disruption"]
C9ORF72["C9ORF72"] -->|increases risk| Familial_ALS["Familial ALS"]
C9ORF72_2["C9ORF72"] -->|co discussed| HSP70["HSP70"]
C9ORF72_3["C9ORF72"] -->|co discussed| TAU["TAU"]
style C9orf72 fill:#ce93d8,stroke:#333,color:#000
style DPR_proteins fill:#4fc3f7,stroke:#333,color:#000
style C9orf72_1 fill:#ce93d8,stroke:#333,color:#000
style ALS_FTD fill:#ef5350,stroke:#333,color:#000
style C9orf72_DPR_neutralizing_ fill:#4fc3f7,stroke:#333,color:#000
style TDP_43_phase_separation_d fill:#4fc3f7,stroke:#333,color:#000
style C9ORF72 fill:#ce93d8,stroke:#333,color:#000
style Familial_ALS fill:#ef5350,stroke:#333,color:#000
style C9ORF72_2 fill:#ce93d8,stroke:#333,color:#000
style HSP70 fill:#ce93d8,stroke:#333,color:#000
style C9ORF72_3 fill:#ce93d8,stroke:#333,color:#000
style TAU fill:#ce93d8,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for C9ORF72 yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for C9orf72.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.