Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.06 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (100 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: nerispirdine, amifampridine phosphate, amifampridine +5 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 1,063 | 0.85 |
| pathways Reactome | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress KCNQ2 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 KCNQ2 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
- KCNQ2 in dopamine neurons, braak-0.30 (p 0.436) → -0.08 (p 0.840)receipt 4595
- KCNQ2 in oligodendrocytes, braak-0.46 (p 0.217) → -0.09 (p 0.821)receipt 4594
Swarm cases
receipt 4595: KCNQ2 in dopamine neurons, braak
- power
- full sample -0.19 (p 0.460, n 18), 95% CI -0.60 to +0.31. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.18 (p 0.471, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.24 (p 0.337, n 18). could be the mix.
- skeptic
- leave-one-out range -0.30 to -0.08, sign flips 0; without severely affected donors -0.19 (p 0.460, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNQ2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 4594: KCNQ2 in oligodendrocytes, braak
- power
- full sample -0.31 (p 0.218, n 18), 95% CI -0.68 to +0.19. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.22 (p 0.389, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.36 (p 0.142, n 18). could be the mix.
- skeptic
- leave-one-out range -0.42 to -0.20, sign flips 0; without severely affected donors -0.31 (p 0.218, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNQ2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts