Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in neutrophils | 0.75 |
| chemistry Open Targets | compounds already reach it: dronedarone, dronedarone hydrochloride | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 536 | 0.91 |
| pathways Reactome | 5 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress KCNJ2 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 KCNJ2 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.
Sealed predictions
- KCNJ2 in dopamine neurons, braak-0.04 (p 0.927) → +0.30 (p 0.428)receipt 11518
- KCNJ2 in oligodendrocytes, braak+0.31 (p 0.421) → +0.32 (p 0.407)receipt 11517
Swarm cases
receipt 11518: KCNJ2 in dopamine neurons, braak
- power
- full sample +0.11 (p 0.677, n 18), 95% CI -0.38 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.08 (p 0.761, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.13 (p 0.597, n 18). could be the mix.
- skeptic
- leave-one-out range +0.02 to +0.27, sign flips 0; without severely affected donors +0.11 (p 0.677, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNJ2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11517: KCNJ2 in oligodendrocytes, braak
- power
- full sample +0.41 (p 0.095, n 18), 95% CI -0.08 to +0.73. 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
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.52 (p 0.027, n 18). not the mix.
- skeptic
- leave-one-out range +0.32 to +0.55, sign flips 0; without severely affected donors +0.41 (p 0.095, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNJ2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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