Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.65 (overall 0.40) | 0.65 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 28 Parkinson's papers of 91 | 0.56 |
| pathways Reactome | 4 pathways; mostly energy | 0.60 |
Knock down and overexpress MCCC1 in a dopamine neuron, astrocyte and microglia tri-culture; measure oxygen consumption rate and ATP output 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
- oxygen consumption rate and ATP output
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves oxygen consumption rate 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 MCCC1 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- MCCC1 in dopamine neurons, braak+0.09 (p 0.820) → +0.22 (p 0.569)receipt 0634
Swarm cases
receipt 0634: MCCC1 in dopamine neurons, braak
- power
- full sample +0.11 (p 0.652, n 18), 95% CI -0.37 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.12 (p 0.646, 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 +0.00 to +0.19, sign flips 3; without severely affected donors +0.11 (p 0.652, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MCCC1 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
loading the receipts