Fig. 4

(A) GCase activity in doxycycline-inducible Tau-mCherry human fibroblasts with the genotype GBA^WT(XX) or GBA1^{L444P/L444P(I)}α (mean ± SD normalized on GBA^WT(XX), n = 7). Mann-Whitney test, *** p 0.0006. (B) GT-02216 dose-response on Tau- GBA1^{L444P/L444P(I)}α fibroblasts (mean ± sem normalized on vehicle, n = 8) treated for 4 days. Non-linear fit with four parameters log(agonist); EC₅₀ = 1.1 µmol/L (0.7–1.6 µmol/L 95% confidentiality interval, top 1.5–1.6 µmol/L, R² = 0.79). (C) Basal and GT-02166-rescued GCase activity is not affected by the induction of Tau-mCherry expression with doxycycline in Tau-GBA1^WT(XX) fibroblasts (mean ± SD normalized on basal ctrl, n = 3). 2way ANOVA (p < .0001 for treatment, ns for Tau expression) and Šidák’s multiple tests against the respective ctrl, **** p < .0001. (D) GT-02216 dose-response on Tau-GBA1^WT(XX) fibroblasts (mean ± sem normalized on vehicle, n = 8) treated for 4 days. Non-linear fit with four parameters log(agonist); EC₅₀ = 1.0 µmol/L (0.7–2.3 µmol/L 95% confidentiality interval, top 1.4–1.6 µmol/L, R² = 0.78).