Fig. 2

(A) Basal GCase activity in wild-type and mutant GBA1 fibroblasts (mean ± SD normalized on GBA1^WT(XY), n = 6–48). Ordinary 1way ANOVA (p < .0001) and Dunnet’s multiple tests against GBA1^WT(XY), **** p < .0001. (B) Effect of 4-days treatment with 12.5 µmol/L GT-02216 on GCase activity on fibroblast lines (mean ± SD normalized on the respective basal activity, n = 5–42). Ordinary 1way ANOVA (p < .0001) and Šidák’s multiple tests against the respective basal activity, **** p < .0001. (C) GT-02216 dose-response on GBA1^{L444P/L444P(I)}α fibroblasts (mean ± sem normalized on vehicle, n = 14) or (D) on GBA1^{WT (XY)} fibroblasts (mean ± sem normalized on vehicle, n = 8) treated for 4 days. Non-linear fit with four parameters log(agonist); EC₅₀ = 2.4 µmol/L on GBA1^{L444P/L444P(I)}α (1.3–10.5 µmol/L 95% confidentiality interval, top 1.8–2.4 µmol/L, R² = 0.71) and 1.5 µmol/L on GBA1^WT(XY) (1.3–1.8 µmol/L 95% confidentiality interval, top 1.9-2.0 µmol/L, R² = 0.95).