Fig. 1.

PXL770 treatment improves VLCFA levels in C-ALD and AMN patient-derived fibroblasts. Fibroblasts were isolated from individual patients with AMN (A) and C-ALD (B, C). (A) AMN fibroblasts were exposed for 7 days to PXL770 at 0.1, 0.5, 1, 2, 3.5, 5, 10, 25, and 50 μM or to Metformin at 100, 200, 300, and 400 μM. VLCFA levels were analyzed by LC-MS after extraction of total lipids from pelleted cells. Fibroblasts from a healthy donor, a C-ALD patient (B) or an AMN patient (C) were exposed to control media or the indicated concentrations of PXL770 followed by LC-MS measurements of specific lipids and the ratio of C26:0/C22:0 VLCFA as described for (A). Data are mean ± S.E.M. n = 5 replicates for (A), 3 for (B), and 5 for (C). Similar results were obtained in two additional independent experiments with these same patient donor cell lines. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001 versus C-ALD/AMN untreated (Dunnett’s test).