Trends in drug development for rare and intractable diseases based on the KEGG NETWORK.

The pathophysiological mechanisms underlying many rare and intractable diseases remain unclear, and there are few drugs for the treatment of these diseases. An understanding of approved drugs is important to improve drug development. In DDrare (Database of Drug Development for Rare Diseases), the targets of drugs in clinical trials are mapped to the KEGG PATHWAY to be grasped on molecular networks. In this study, to understand the relationship between drug targets and disease genes, we mapped them to the KEGG NETWORK (networks) defined as functionally meaningful segments of pathways. We found that disease genes tended to be included in networks characteristic for each disease group, whereas drug targets were mapped to networks common to many disease groups. The number of drugs targeting the networks containing disease genes was small in every disease group. However, because several studies have recently addressed that the drugs targeting proteins with genetic evidence of disease association are more likely to be approved, we confirmed the results using the KEGG NETWORK and integrating the risk genes obtained from the latest GWAS data. The results were clearer and more detailed than those of previous studies, which suggests a direction for future drug development.