Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.25 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in thymic myoid cells | 0.75 |
| chemistry Open Targets | compounds already reach it: terodiline hydrochloride, terodiline, suloctidil +7 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 5 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress CACNB1 in astrocytes; measure evoked dopamine release and dopamine transporter uptake and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- 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 degradation, and dopamine neuron survival in co-culture
- 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 CACNB1 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CACNB1 in dopamine neurons, braak-0.42 (p 0.258) → -0.21 (p 0.586)receipt 1673
- CACNB1 in astrocytes, braak-0.27 (p 0.487) → -0.58 (p 0.101)receipt 1672
Swarm cases
receipt 1673: CACNB1 in dopamine neurons, braak
- power
- full sample -0.54 (p 0.020, n 18), 95% CI -0.81 to -0.10. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.56 (p 0.016, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.72 (p 7.0e-4, n 18). not the mix.
- skeptic
- leave-one-out range -0.67 to -0.48, sign flips 0; without severely affected donors -0.54 (p 0.020, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CACNB1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 1672: CACNB1 in astrocytes, braak
- power
- full sample -0.37 (p 0.130, n 18), 95% CI -0.71 to +0.12. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.39 (p 0.111, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.30 (p 0.221, n 18). could be the mix.
- skeptic
- leave-one-out range -0.55 to -0.29, sign flips 0; without severely affected donors -0.37 (p 0.130, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CACNB1 in astrocytes.
case closed: nothing better to follow up.
Receipts
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