Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.54 from other evidence | 0.00 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | compounds already reach it: me-344, metformin hydrochloride, metformin | 1.00 |
| trials ClinicalTrials.gov | 4 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 3 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress NDUFC2 in a dopamine neuron, astrocyte and microglia tri-culture; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) 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 NDUFC2 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.61; 2026-10-25 0.61; 2026-10-24 0.61; 2026-10-23 0.61.
Sealed predictions
- NDUFC2 in dopamine neurons, braak-0.45 (p 0.003) → -0.60 (p 3.2e-5)held
- NDUFC2 in dopamine neurons, braak-0.13 (p 0.739) → +0.26 (p 0.502)receipt 0597
- NDUFC2 in dopamine neurons, resilience+0.10 (p 0.720) → +0.29 (p 0.282)receipt 0147
Swarm cases
receipt 0597: NDUFC2 in dopamine neurons, braak
- power
- full sample +0.07 (p 0.774, n 18), 95% CI -0.41 to +0.52. 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: +0.13 (p 0.621, n 18). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.20, sign flips 3; without severely affected donors +0.07 (p 0.774, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFC2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0147: NDUFC2 in dopamine neurons, resilience
- power
- full sample +0.23 (p 0.239, n 55), 95% CI -0.04 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: +0.28 (p 0.152, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.20 (p 0.313, n 55). could be the mix.
- skeptic
- leave-one-out range +0.18 to +0.31, sign flips 0; without severely affected donors +0.17 (p 0.388, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- braak beats resilience for NDUFC2 in dopamine neurons: -0.53 (p 1.8e-7, n 84). proposing braak.
case closed: every proposal failed a challenge.
Receipts
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