Fig. 2
Drug screen of cytoprotective candidates. a VWMD1 EIF2B5R113H/A403V disease fibroblasts were coincubated with MG132 and each of 2400 drugs from an FDA-approved drug library. Cell viability was measured and normalised to cell viability with MG132 stressor in the absence of drug. Drugs were scored based on increase in cell viability with threshold set to > 1.5× standard deviation (n = 3). Cytoprotection ranged from 2-fold increase in viability to 0 (100% cell death for cytotoxic drugs). Horizontal dotted red line indicates 1.5 × standard deviation of MG132 stressed controls. b Hit candidates were taken forward to assess their dose-response effect on cell viability of VWMD1 EIF2B5R113H/A403V fibroblasts and iPSC-derived astrocytes, relative to MG132 stress (n = 5–6). Heat map represents cytoprotection (blue) versus cytotoxicity (red) of individual drugs