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 oligodendrocyte progenitor cells (30 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: neramexane mesylate, orphenadrine citrate, ralfinamide +24 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 127 | 0.82 |
| pathways Reactome | 8 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress GRIN2D in oligodendrocytes; measure evoked dopamine release and dopamine transporter uptake and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- 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 myelin basic protein output under oxidative stress
- 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 GRIN2D in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; α-synuclein uptake and myelin basic protein output under oxidative stress. 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
- GRIN2D in oligodendrocytes, braak-0.24 (p 0.533) → -0.16 (p 0.682)receipt 0554
- GRIN2D in dopamine neurons, braak-0.12 (p 0.756) → -0.57 (p 0.109)receipt 0555
- GRIN2D in oligodendrocytes, resilience-0.43 (p 0.133) → -0.15 (p 0.584)receipt 0078
- GRIN2D in oligodendrocytes, braak-0.10 (p 0.512) → +0.35 (p 0.024)receipt 0077
Swarm cases
receipt 0555: GRIN2D in dopamine neurons, braak
- power
- full sample -0.36 (p 0.145, n 18), 95% CI -0.71 to +0.13. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.38 (p 0.120, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.42 (p 0.080, n 18). could be the mix.
- skeptic
- leave-one-out range -0.52 to -0.30, sign flips 0; without severely affected donors -0.36 (p 0.145, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2D in dopamine neurons.
case closed: nothing better to follow up.
receipt 0554: GRIN2D in oligodendrocytes, braak
- power
- full sample -0.11 (p 0.671, n 18), 95% CI -0.55 to +0.38. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.08 (p 0.748, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.29 (p 0.243, n 18). could be the mix.
- skeptic
- leave-one-out range -0.22 to +0.01, sign flips 3; without severely affected donors -0.11 (p 0.671, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2D in oligodendrocytes.
case closed: nothing better to follow up.
receipt 0078: GRIN2D in oligodendrocytes, resilience
- power
- full sample -0.34 (p 0.084, n 55), 95% CI -0.55 to -0.08. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: -0.30 (p 0.125, n 55). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis -0.52 (p 0.0075); controlling for it: -0.33 (p 0.088, n 55). could be the mix.
- skeptic
- leave-one-out range -0.41 to -0.29, sign flips 0; without severely affected donors -0.39 (p 0.052, n 46). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for GRIN2D in oligodendrocytes.
case closed: nothing better to follow up.
receipt 0077: GRIN2D in oligodendrocytes, braak
- power
- full sample +0.11 (p 0.337, n 84), 95% CI -0.11 to +0.31. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: +0.14 (p 0.204, n 84). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.09 (p 0.422); controlling for it: +0.16 (p 0.143, n 84). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.14, sign flips 0; without severely affected donors +0.14 (p 0.246, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GRIN2D in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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