Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.73 (overall 0.47) | 0.73 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in plasma cells | 0.75 |
| chemistry Open Targets | compounds already reach it: isatuximab, felzartamab, daratumumab +1 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 33 Parkinson's papers of 11,350 | 0.54 |
| pathways Reactome | 1 pathway; mostly energy | 0.60 |
Knock down and overexpress CD38 in astrocytes; measure oxygen consumption rate and ATP output 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
- oxygen consumption rate and ATP output
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- 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 CD38 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; 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
- CD38 in astrocytes, braak-0.16 (p 0.685) → -0.04 (p 0.928)receipt 0308
- CD38 in dopamine neurons, braak-0.02 (p 0.965) → +0.38 (p 0.309)receipt 0309
Swarm cases
receipt 0309: CD38 in dopamine neurons, braak
- power
- full sample +0.16 (p 0.538, n 18), 95% CI -0.34 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.20 (p 0.418, 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 0.603, n 18). could be the mix.
- skeptic
- leave-one-out range +0.06 to +0.30, sign flips 0; without severely affected donors +0.16 (p 0.538, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CD38 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0308: CD38 in astrocytes, 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: -0.09 (p 0.728, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.08 (p 0.761, n 18). could be the mix.
- skeptic
- leave-one-out range -0.27 to -0.01, sign flips 0; 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 CD38 in astrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts