Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.32 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including brain excitatory neurons; strongest in retinal bipolar cells | 0.75 |
| chemistry Open Targets | compounds already reach it: sevoflurane, estazolam, adipiplon +71 | 1.00 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | 4 Parkinson's papers of 410 | 0.79 |
| pathways Reactome | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress GABRB3 in dopamine neurons; measure evoked dopamine release and dopamine transporter uptake 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
- evoked dopamine release and dopamine transporter uptake
- 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 evoked dopamine release 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 GABRB3 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; 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
- GABRB3 in dopamine neurons, braak-0.18 (p 0.648) → +0.91 (p 5.9e-4)receipt 1084
Swarm cases
receipt 1084: GABRB3 in dopamine neurons, braak
- power
- full sample +0.60 (p 0.0089, n 18), 95% CI +0.18 to +0.83. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.62 (p 0.0062, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.71 (p 8.7e-4, n 18). not the mix.
- skeptic
- leave-one-out range +0.54 to +0.69, sign flips 0; without severely affected donors +0.60 (p 0.0089, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GABRB3 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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