Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.61 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (149 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: ralfinamide, cns-5161, perzinfotel +24 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 78 | 0.82 |
| pathways Reactome | 6 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress GRIN2C in astrocytes; measure evoked dopamine release and dopamine transporter uptake and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- 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
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- 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 GRIN2C in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.66; 2026-10-25 0.66; 2026-10-24 0.66; 2026-10-23 0.66.
Sealed predictions
- GRIN2C in astrocytes, braak-0.39 (p 0.297) → -0.03 (p 0.946)receipt 0548
- GRIN2C in dopamine neurons, braak-0.30 (p 0.428) → -0.43 (p 0.251)receipt 0549
- GRIN2C in astrocytes, braak-0.10 (p 0.521) → +0.01 (p 0.967)receipt 0068
- GRIN2C in astrocytes, resilience-0.40 (p 0.275) → +0.32 (p 0.190)receipt 0069
Swarm cases
receipt 0549: GRIN2C in dopamine neurons, braak
- power
- full sample -0.39 (p 0.109, n 18), 95% CI -0.73 to +0.09. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.42 (p 0.084, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.57 (p 0.014, n 18). not the mix.
- skeptic
- leave-one-out range -0.47 to -0.31, sign flips 0; without severely affected donors -0.39 (p 0.109, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2C in dopamine neurons.
case closed: nothing better to follow up.
receipt 0548: GRIN2C in astrocytes, braak
- power
- full sample -0.10 (p 0.696, n 18), 95% CI -0.54 to +0.39. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.12 (p 0.627, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.10 (p 0.702, n 18). could be the mix.
- skeptic
- leave-one-out range -0.24 to +0.02, sign flips 1; without severely affected donors -0.10 (p 0.696, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2C in astrocytes.
case closed: nothing better to follow up.
receipt 0069: GRIN2C in astrocytes, resilience
- power
- full sample +0.10 (p 0.628, n 55), 95% CI -0.17 to +0.35. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: +0.10 (p 0.628, n 55). does not hold up.
- composition
- astrocytes share of nuclei vs axis +0.34 (p 0.084); controlling for it: +0.07 (p 0.736, n 55). could be the mix.
- skeptic
- leave-one-out range +0.01 to +0.19, sign flips 0; without severely affected donors +0.09 (p 0.671, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for GRIN2C in astrocytes.
case closed: nothing better to follow up.
receipt 0068: GRIN2C in astrocytes, braak
- power
- full sample -0.05 (p 0.629, n 84), 95% CI -0.26 to +0.16. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: -0.07 (p 0.507, n 84). does not hold up.
- composition
- astrocytes share of nuclei vs axis +0.26 (p 0.016); controlling for it: -0.10 (p 0.365, n 84). could be the mix.
- skeptic
- leave-one-out range -0.09 to -0.03, sign flips 0; without severely affected donors -0.03 (p 0.790, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2C in astrocytes.
case closed: nothing better to follow up.
Receipts
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