Finding the repurpose
A Stanford University team has used a computational approach to analyze publicly available gene expression profiles and identified two drug repurposing opportunities. 1,2 The researchers found that the anticonvulsant topiramate could have use in inflammatory bowel disease and that the generic ulcer drug cimetidine could help treat lung adenocarcinoma. The computational method is exclusively licensed to NuMedii Inc., a bioinformatics spinout from Stanford that is using the technology to evaluate
... molecular data to repurpose drugs. The Stanford group used previously published gene expression data from 100 diseases and 164 drugs to confirm already known therapeutic uses and to predict the potential of the drugs to treat new indications (see Figure 1 , "Schematic workflow of drug-disease pairing using gene expression profile similarity"). The computational technique showed that topiramate had a stronger therapeutic score for IBD than prednisolone and that cimetidine had a stronger therapeutic score for lung adenocarcinoma than AstraZeneca plc's Iressa gefitinib. Topiramate, a sulfamate-substituted monosaccharide that acts as a sodium channel blocker, g-aminobutyric acid receptor (GABAR) agonist and AMPAR antagonist, is marketed to treat epilepsy, seizures and migraines. The drug is available as a generic and is marketed as Topamax by Johnson & Johnson. Iressa, an epidermal growth factor receptor (EGFR) inhibitor, is marketed in the EU to treat non-small cell lung cancer (NSCLC). In a second in silico study, the researchers specifically focused on IBD. Using only the gene expression data from IBD patient samples and those of the 164 drug compounds, they again confirmed that topiramate had a stronger IBD therapeutic score than prednisolone. The IBD and lung cancer results also were borne out in placebocontrolled animal studies. In a rat model of IBD, topiramate lowered the incidence of diarrhea and IBD-related colitis compared with saline.