Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in medullary thymic epithelial cells | 0.75 |
| chemistry Open Targets | compounds already reach it: tiagabine hydrochloride, tiagabine | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 229 | 0.82 |
| pathways Reactome | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress SLC6A1 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 SLC6A1 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
- SLC6A1 in astrocytes, braak+0.11 (p 0.773) → +0.05 (p 0.906)receipt 3526
- SLC6A1 in dopamine neurons, braak-0.04 (p 0.928) → -0.22 (p 0.563)receipt 3527
Swarm cases
receipt 3527: SLC6A1 in dopamine neurons, braak
- power
- full sample -0.17 (p 0.493, n 18), 95% CI -0.59 to +0.32. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.17 (p 0.493, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.19 (p 0.455, n 18). could be the mix.
- skeptic
- leave-one-out range -0.33 to -0.05, sign flips 0; without severely affected donors -0.17 (p 0.493, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC6A1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3526: SLC6A1 in astrocytes, braak
- power
- full sample +0.13 (p 0.615, n 18), 95% CI -0.36 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.11 (p 0.658, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.18 (p 0.476, n 18). could be the mix.
- skeptic
- leave-one-out range -0.01 to +0.25, sign flips 1; without severely affected donors +0.13 (p 0.615, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLC6A1 in astrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts