Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.77 (overall 0.59) | 0.77 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | hard to drug | 0.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 115 Parkinson's papers of 211 | 0.38 |
| pathways Reactome | 2 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress CHCHD2 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.
- 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 CHCHD2 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 0.59; 2026-10-25 0.59; 2026-10-24 0.59; 2026-10-23 0.59.
Sealed predictions
- CHCHD2 in dopamine neurons, braak+0.33 (p 0.389) → -0.27 (p 0.476)receipt 0565
- CHCHD2 in dopamine neurons, braak-0.12 (p 0.463) → +0.03 (p 0.831)receipt 0094
- CHCHD2 in dopamine neurons, resilience+0.46 (p 0.087) → +0.20 (p 0.497)receipt 0095
In the sealed studies
- Mitochondrial quality control and Lewy stage: did not hold
Swarm cases
receipt 0565: CHCHD2 in dopamine neurons, braak
- power
- full sample +0.01 (p 0.956, n 18), 95% CI -0.46 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.06 (p 0.814, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.16 (p 0.515, n 18). could be the mix.
- skeptic
- leave-one-out range -0.11 to +0.13, sign flips 7; without severely affected donors +0.01 (p 0.956, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CHCHD2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0095: CHCHD2 in dopamine neurons, resilience
- power
- full sample +0.34 (p 0.081, n 55), 95% CI +0.09 to +0.56. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: +0.36 (p 0.064, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.39 (p 0.048, n 55). not the mix.
- skeptic
- leave-one-out range +0.30 to +0.41, sign flips 0; without severely affected donors +0.35 (p 0.087, n 46). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for CHCHD2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0094: CHCHD2 in dopamine neurons, braak
- power
- full sample -0.03 (p 0.779, n 84), 95% CI -0.24 to +0.18. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: -0.01 (p 0.926, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: -0.05 (p 0.624, n 84). could be the mix.
- skeptic
- leave-one-out range -0.06 to +0.00, sign flips 1; without severely affected donors +0.01 (p 0.910, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CHCHD2 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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