Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.33 (overall 0.21) | 0.33 |
| cell type Human Protein Atlas | cell type enriched in brain excitatory neurons (35 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: crinecerfont, ono-2333ms, emicerfont +2 | 0.90 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | 14 Parkinson's papers of 1,090 | 0.64 |
| pathways Reactome | 2 pathways; mostly other | 0.30 |
Knock down and overexpress CRHR1 in dopamine neurons; measure a transcriptome-wide state shift (bulk RNA-seq) and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of CRHR1 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CRHR1 in dopamine neurons, braakn/a → n/areceipt 1963
Swarm cases
receipt 1963: CRHR1 in dopamine neurons, braak
- cell type
- CRHR1 is not measured in dopamine neurons; looking elsewhere.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CRHR1 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
loading the receipts