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, including oligodendrocytes; strongest in somatotrophs | 0.75 |
| chemistry Open Targets | compounds already reach it: dalfampridine, nerispirdine, guanidine hydrochloride +3 | 1.00 |
| trials ClinicalTrials.gov | 8 Parkinson's trials, 1 stopped | 0.90 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 1 pathway; mostly dopamine synapse | 1.00 |
Knock down and overexpress KCNH8 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 KCNH8 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
- KCNH8 in oligodendrocytes, braak+0.32 (p 0.406) → -0.28 (p 0.464)receipt 4736
- KCNH8 in dopamine neurons, braak-0.47 (p 0.197) → +0.82 (p 0.007)receipt 4737
Swarm cases
receipt 4737: KCNH8 in dopamine neurons, braak
- power
- full sample +0.24 (p 0.328, n 18), 95% CI -0.25 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.21 (p 0.398, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.12 (p 0.646, n 18). could be the mix.
- skeptic
- leave-one-out range +0.15 to +0.39, sign flips 0; without severely affected donors +0.24 (p 0.328, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNH8 in dopamine neurons.
case closed: nothing better to follow up.
receipt 4736: KCNH8 in oligodendrocytes, braak
- power
- full sample -0.00 (p 0.990, n 18), 95% CI -0.47 to +0.46. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.04 (p 0.881, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.05 (p 0.847, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.12, sign flips 7; without severely affected donors -0.00 (p 0.990, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNH8 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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