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 (2969 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: guanidine hydrochloride, amifampridine phosphate, tedisamil +3 | 1.00 |
| trials ClinicalTrials.gov | 6 Parkinson's trials, 1 stopped | 0.87 |
| literature PubMed | 1 Parkinson's papers of 115 | 0.91 |
| pathways Reactome | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress KCND2 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 KCND2 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
- KCND2 in oligodendrocytes, braak-0.27 (p 0.487) → +0.12 (p 0.756)receipt 4658
- KCND2 in dopamine neurons, braak+0.47 (p 0.204) → +0.31 (p 0.414)receipt 4659
Swarm cases
receipt 4659: KCND2 in dopamine neurons, braak
- power
- full sample +0.34 (p 0.170, n 18), 95% CI -0.15 to +0.70. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.33 (p 0.188, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.31 (p 0.211, n 18). could be the mix.
- skeptic
- leave-one-out range +0.26 to +0.50, sign flips 0; without severely affected donors +0.34 (p 0.170, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCND2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 4658: KCND2 in oligodendrocytes, braak
- power
- full sample -0.11 (p 0.664, n 18), 95% CI -0.55 to +0.38. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.16 (p 0.532, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.07 (p 0.774, n 18). could be the mix.
- skeptic
- leave-one-out range -0.24 to +0.01, sign flips 2; without severely affected donors -0.11 (p 0.664, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KCND2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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