Unraveling Novel Drug candidate for ALS through an Integrative Network Analysis of approved Drug-Gene Expression Signatures in Human Pluripotent Stem Cell-Based Model

Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of 'old' drugs to treat both common and rare diseases is increasingly becoming an attractive proposition. In this study, we evaluated the potential of using human pluripotent stem cells to identify repurposable drug candidates. For this purpose, we treated derivatives from human embryonic stem cells with 50 marketed drugs and we annotated the induced molecular changes by RNA deep sequencing. Focusing on genes previously implicated in monogenic diseases, we identified drugs capable of modulating the expression of PLP1, PMP22, LMNB1 and SQSTM1 genes known to be involved in Pelizaeus-Merzbacher disease (PMP), hereditary neuropathy with liability to pressure palsies (HNPP), adult-onset autosomal dominant leukodystrophy (ALDL) and amyotrophic lateral sclerosis (ALS).