| Gene Symbol | ent-gene-95250f02 |
| Model | iPSC-derived microglia + dopaminergic neurons from PD patients (LRRK2 G2019S, idiopathic, GBA carriers) and healthy controls |
| Condition Groups | Control, PD neurons only, PD neurons + cGAS activators (dsDNA transfection), PD neurons + cGAS-STING inhibitors (G150, H151) |
| Readouts | - Behavioral: cylinder test, stepping test, gait analysis, rotarod - Biochemical: striatal dopamine, TH+ neuron counts in SNc - Molecular: cGAS-STING pathway activation (cGAMP, p-STING) - Type I IFN markers: IFN-β, ISG56 - Inflammation: Iba1+ microglial density, cytokine levels - α-synuclein pathology: pSer129 burden |
| Models | MPTP-induced PD model, α-synuclein pre-formed fibril (PFF) model, PINK1 knockout (mtDNA release model) |
| Treatment Groups | Vehicle, cGAS inhibitor (G150, 30mg/kg i.p. daily), STING inhibitor (H151, 10mg/kg i.p. daily), Positive control (L-DOPA) |
| Duration | 52 weeks |
| Cohort | 400 PD patients (various stages), 150 controls |
| Samples | CSF, plasma, peripheral blood mononuclear cells (PBMCs) |
| Biomarkers | cGAMP (CSF and plasma), STING, p-STING, IFN-β, ISG56, CXCL10 in CSF; genetic variants in cGAS/STING genes |
| Correlation | UPDRS motor score, MoCA, DAT-SPECT imaging, disease progression rate |
| Design | Randomized, double-blind, placebo-controlled |
| Primary Endpoint | Biomarker levels vs. clinical measures |
| Secondary | Biomarker changes over 24-month follow-up |
| Population | Early-stage PD (Hoehn & Yahr 1-2) with elevated cGAMP or IFN markers |
| Intervention | STING inhibitor (to be determined based on BBB penetration) or placebo |
| KG Connections | 2 knowledge graph edges |
| Databases | GeneCardsUniProtNCBI GeneHPASTRING |