Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.03 (overall 0.06) | 0.03 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (31 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: nerispirdine, guanidine hydrochloride, amifampridine +3 | 1.00 |
| trials ClinicalTrials.gov | 6 Parkinson's trials, 1 stopped | 0.87 |
| 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 KCNF1 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 KCNF1 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
- KCNF1 in dopamine neurons, braak-0.53 (p 0.140) → +0.41 (p 0.272)receipt 4441
- KCNF1 in oligodendrocytes, braakn/a → n/areceipt 4440
Swarm cases
receipt 4441: KCNF1 in dopamine neurons, braak
- power
- full sample +0.03 (p 0.901, n 18), 95% CI -0.44 to +0.49. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.07 (p 0.774, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.05 (p 0.854, n 18). could be the mix.
- skeptic
- leave-one-out range -0.09 to +0.14, sign flips 5; without severely affected donors +0.03 (p 0.901, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNF1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 4440: KCNF1 in oligodendrocytes, braak
- cell type
- KCNF1 is not measured in oligodendrocytes; looking elsewhere.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCNF1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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