Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.44 from other evidence | 0.00 |
| cell type Human Protein Atlas | enriched in the midbrain (173 nTPM), where the nigral dopamine neurons sit | 0.90 |
| chemistry Open Targets | compounds already reach it: valbenazine tosylate, benzphetamine, dextroamphetamine sulfate +11 | 1.00 |
| trials ClinicalTrials.gov | 6 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | 52 Parkinson's papers of 170 | 0.48 |
| pathways Reactome | 3 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress SLC18A2 in dopamine neurons; measure evoked dopamine release and dopamine transporter uptake and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- 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
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- 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 SLC18A2 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- SLC18A2 in dopamine neurons, braak-0.12 (p 0.749) → -0.25 (p 0.514)receipt 0455
In the sealed studies
Swarm cases
receipt 0455: SLC18A2 in dopamine neurons, braak
- power
- full sample -0.18 (p 0.471, n 18), 95% CI -0.60 to +0.31. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.32 (p 0.194, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.32 (p 0.194, n 18). could be the mix.
- skeptic
- leave-one-out range -0.32 to -0.07, sign flips 0; without severely affected donors -0.18 (p 0.471, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC18A2 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
loading the receipts