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Hypotheses

Top-ranked hypotheses by composite score. Filter by lifecycle status, disease, or target gene; sort by score or recency. Click a row to open evidence, scoring detail, and any live prediction markets referencing it.

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#HypothesisTarget geneStatusCompositeUpdated
1ASO-mediated reduction of toxic C9orf72 dipeptide repeat proteins in ALS/FTD
neurodegeneration 5 ev
h-c56d4f6a1a
C9orf72proposed—2026-05-14Open →
2circRNA dysregulation as neurodegeneration biomarker and exploratory therapeuti…
neurodegeneration 5 ev
h-629ae6fdc0
circHomer1; circCfl1; ALKBH5; YTHDF2proposed—2026-05-14Open →
3Agonistic antibodies targeting TREM2 to shift microglia toward neuroprotective…
neurodegeneration 5 ev
h-25193345a5
TREM2proposed—2026-05-14Open →
4Pharmacologic SARM1 blockade to prevent Wallerian degeneration after axotomy
neurodegeneration 5 ev
h-0c78964fbd
SARM1proposed—2026-05-14Open →
5Astrocyte GAT-3 dysfunction and inhibitory-network disruption in ALS/FTD
neurodegeneration 5 ev
h-ed53359485
SLC6A13; SLC12A5; SLC12A2proposed—2026-05-14Open →
6HDAC6 Inhibition for Charcot-Marie-Tooth Disease and ALS
neurodegeneration 8 ev
h-3fcd326bc1
HDAC6proposed—2026-05-14Open →
7Lysosomal GBA1 Enhancement via Glucosylceramide Reduction
neurodegeneration 7 ev
h-6b3f1b4b3e
GBA1proposed—2026-05-14Open →
8Glial-Specific Ferroptosis Resistance via GPX4 Enhancement Protects Motor Neuro…
neurodegeneration 6 ev
h-ebf3cb4d54
GPX4proposed—2026-05-14Open →
9TDP-43 Phase Separation Destabilization Drives Cytoplasmic Aggregation
neurodegeneration 6 ev
h-4978202a55
TDP-43 (TARDBP), PRMT5proposed—2026-05-14Open →
10Perineuronal Net Depolymerization as Early Synaptic Vulnerability Trigger
neurodegeneration 6 ev
h-bfbc071096
CSPG, MMP-9, aggrecanproposed—2026-05-14Open →
11TREM2-CX3CR1 Axis Dysregulation in Microglial Surveillance Failure
neurodegeneration 6 ev
h-506d813344
TREM2, CX3CR1proposed—2026-05-14Open →
12CSF1R Agonism for TREM2-Independent Microglial Activation in ALS
neurodegeneration 6 ev
h-d0228dd1a8
CSF1Rproposed—2026-05-14Open →
13Serotonergic 5-HT1A/1B Agonism for Neuroprotection
neurodegeneration 6 ev
h-6d75f21bc9
SLC6A4 (SERT), HTR1A, HTR1Bproposed—2026-05-14Open →
14OPC exhaustion and failed remyelination in progressive multiple sclerosis
neurodegeneration 5 ev
h-f714b6f6aa
PDGFRA; CSPG4; CDKN2A; CDKN1A; GATA3proposed—2026-05-14Open →
15ATXN2 Antisense Oligonucleotides Reduce Dipeptide Repeat Proteins in C9orf72-AL…
neurodegeneration 6 ev
h-e9db71317e
ATXN2proposed—2026-05-14Open →
16Microglial IKKβ Inhibition to Block NF-κB-Mediated Inflammation
neurodegeneration 5 ev
h-65b13bc5c9
IKKβ (CHUK)proposed—2026-05-14Open →
17TREM2 Agonism for Alzheimer's Disease
neurodegeneration 8 ev
h-3924cdba57
TREM2proposed—2026-05-14Open →
18LAMP2A-Mediated Autophagy Enhancement Blocks Alpha-Synuclein Propagation in Par…
neurodegeneration 6 ev
h-7336d351b0
LAMP2Aproposed—2026-05-14Open →
19Nrf2 Pathway Activation Compensates for Progranulin Haploinsufficiency in FTD-G…
neurodegeneration 6 ev
h-0bed611702
NFE2L2proposed—2026-05-14Open →
20C9orf72 Nucleocytoplasmic Transport Rescue for ALS/FTD
neurodegeneration 8 ev
h-fc7311c6be
C9orf72proposed—2026-05-14Open →
21ER-mitochondria contact-site dysfunction in neurodegeneration
neurodegeneration 5 ev
h-df18198e59
MFN2; ITPR1; HSPA9; VDAC1proposed—2026-05-14Open →
22Small-Molecule Modulation of TDP-43 Liquid-Liquid Phase Separation for ALS/FTD
neurodegeneration 6 ev
h-f801d7a726
TARDBPproposed—2026-05-14Open →
23LRRK2 G2019S Kinase Inhibition for Parkinson's Disease
neurodegeneration 7 ev
h-436ff37203
LRRK2proposed—2026-05-14Open →
24Selective p38γ MAPK Inhibition Reduces Pathological Tau Phosphorylation in Alzh…
neurodegeneration 6 ev
h-859dcabc7a
MAPK12proposed—2026-05-14Open →
25Rational design of small molecules targeting TDP-43 liquid-to-solid phase trans…
neurodegeneration 5 ev
h-fc57d8e73d
TARDBPproposed—2026-05-14Open →
26NRF2 pathway activation to reduce mutant huntingtin aggregates and oxidative st…
neurodegeneration 5 ev
h-641d1459da
NFE2L2proposed—2026-05-14Open →
27LRRK2 kinase inhibition to normalize lysosomal trafficking in Parkinson's disea…
neurodegeneration 5 ev
h-c8d21880fc
LRRK2proposed—2026-05-14Open →
28Blood-Brain Barrier Pericyte-to-Mesenchymal Transition Drives Vascular Collapse
neurodegeneration 6 ev
h-2263e00831
PDGFRβ, SNAI2/SLUG, AQP4proposed—2026-05-14Open →
29Glial Metabolic Coupling Failure in Neuronal Bioenergetic Crisis
neurodegeneration 6 ev
h-afdb1b087a
MCT1/MCT4, lactate dehydrogenaseproposed—2026-05-14Open →
30USP13 Stabilization of PINK1/Parkin Mitophagy in Parkinson's Disease
neurodegeneration 7 ev
h-b3ff662404
USP13proposed—2026-05-14Open →
31TREM2-dependent microglial lipid handling in Alzheimer's disease
neurodegeneration 5 ev
h-e20b3e9911
TREM2; APOE; ABCA1proposed—2026-05-14Open →
32Complement C1q/C3 Blockade for Alzheimer's Disease
neurodegeneration 8 ev
h-0bac1b92f6
C1QAproposed—2026-05-14Open →
33Pharmacologic activation of GBA1 to reduce alpha-synuclein burden in Parkinson'…
neurodegeneration 5 ev
h-7881847161
GBA1proposed—2026-05-14Open →
34Glial Progenitor Cell Support in Huntington's Disease
neurodegeneration 7 ev
h-f3593d42c8
HTTproposed—2026-05-14Open →
35Nuclear Pore Complex Integrity as Proteostasis Checkpoint Failure
neurodegeneration 6 ev
h-868a4e91eb
RANBP2/Nup358, importin-βproposed—2026-05-14Open →
36TDP-43 phase-separation and nuclear-function failure in ALS/FTD
neurodegeneration 6 ev
h-bf2e53d730
TARDBP; TIA1proposed—2026-05-14Open →
37TREM2 Microglial Agonism for Enhanced Phagocytosis
neurodegeneration 6 ev
h-869b5707e8
TREM2proposed—2026-05-14Open →
38PINK1/Parkin-pathway mitophagy impairment in sporadic Parkinson's disease
neurodegeneration 5 ev
h-bbc6ede91c
PINK1; PARK2; MFN2; OPTNproposed—2026-05-14Open →
39Pentose Phosphate Pathway Suppression Enables Ferroptosis Vulnerability
neurodegeneration 6 ev
h-ff019d4736
G6PD, SLC7A11, GPX4proposed—2026-05-14Open →
40Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration
neurodegeneration mechanistic 37 ev
h-var-08a4d5c07a
NLRP3, CASP1, IL1B, PYCARDvalidated0.9242026-05-13Open →
41APOE-Dependent Autophagy Restoration
neurodegeneration therapeutic 42 ev
h-51e7234f
MTORvalidated0.8952026-05-16Open →
42Hypothesis 4: Metabolic Coupling via Lactate-Shuttling Collapse
neurodegeneration 11 ev
h-b2ebc9b2
SLC16A1, SLC16A7, LDHA, PDHA1validated0.8952026-05-16Open →
43p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43…
neurodegeneration combination 16 ev
h-ccc05373
MAPK14/PRMT1validated0.8952026-05-16Open →
44SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence
neurodegeneration mechanistic 55 ev
h-var-b7de826706
SIRT1validated0.8932026-05-16Open →
45TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration
neurodegeneration mechanistic 53 ev
h-var-66156774e7
TREM2validated0.8922026-05-16Open →
46Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of…
neurodegeneration 11 ev
h-f1c67177
IFNGvalidated0.8872026-05-16Open →
47TREM2-APOE Axis Dissociation for Selective DAM Activation
neurodegeneration 14 ev
h-5b378bd3
TREM2-APOE axisvalidated0.8862026-05-13Open →
48Circadian Glymphatic Entrainment via Targeted Orexin Receptor Modulation
neurodegeneration therapeutic 29 ev
h-9e9fee95
HCRTR1/HCRTR2validated0.8822026-05-13Open →
49Complement Cascade Inhibition Synaptic Protection
neurodegeneration 15 ev
h-e64a33a8
—validated0.8672026-05-16Open →
50TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Fail…
neurodegeneration 12 ev
h-881bc290
NAMPTvalidated0.8622026-05-16Open →
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Hypothesis index sorted by composite score. Each hypothesis is a scientific claim produced by multi-agent analysis, scored on 10 dimensions. Filter by hypothesis_type, target_gene, disease, or status. Links to /hypotheses/[id] for the full scoring breakdown.

POST /api/scidex/rpc
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