Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.63 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in brain inhibitory neurons (895 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: amantadine, apimostinel, acamprosate +28 | 1.00 |
| trials ClinicalTrials.gov | 50 Parkinson's trials, 9 stopped | 0.86 |
| literature PubMed | 24 Parkinson's papers of 694 | 0.58 |
| pathways Reactome | 11 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress GRIN2B 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 GRIN2B 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.
Earlier readings: 2026-10-26 0.60; 2026-10-25 0.60; 2026-10-24 0.60; 2026-10-23 0.60.
Sealed predictions
- GRIN2B in dopamine neurons, braak+0.16 (p 0.680) → +0.03 (p 0.947)receipt 0534
- GRIN2B in dopamine neurons, resilience-0.11 (p 0.703) → -0.49 (p 0.090)receipt 0045
- GRIN2B in dopamine neurons, braak+0.14 (p 0.385) → -0.11 (p 0.484)receipt 0044
Swarm cases
receipt 0534: GRIN2B in dopamine neurons, braak
- power
- full sample +0.11 (p 0.664, n 18), 95% CI -0.38 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.11 (p 0.664, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.06 (p 0.827, n 18). could be the mix.
- skeptic
- leave-one-out range +0.01 to +0.25, sign flips 0; without severely affected donors +0.11 (p 0.664, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2B in dopamine neurons.
case closed: nothing better to follow up.
receipt 0045: GRIN2B in dopamine neurons, resilience
- power
- full sample -0.29 (p 0.147, n 55), 95% CI -0.51 to -0.02. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: -0.29 (p 0.135, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: -0.32 (p 0.105, n 55). could be the mix.
- skeptic
- leave-one-out range -0.40 to -0.22, sign flips 0; without severely affected donors -0.28 (p 0.160, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for GRIN2B in dopamine neurons.
case closed: nothing better to follow up.
receipt 0044: GRIN2B in dopamine neurons, braak
- power
- full sample -0.00 (p 0.966, n 84), 95% CI -0.22 to +0.21. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: -0.05 (p 0.667, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: +0.03 (p 0.767, n 84). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.03, sign flips 23; without severely affected donors -0.01 (p 0.963, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2B in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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