Finding chemical drugs for genetic diseases

Chemical drugs provide alternative treatments for genetic diseases in addition to gene therapy. Inherited diseases arising from gain-of-function (GOF) or loss-of-function (LOF) mutations of certain genes can be ameliorated by the antagonists and/or agonists of the target genes. However, a premise for this chemical therapeutic strategy is that the GOF/LOF mutations in drug targets have a negligible influence on drug-target binding. Here, we analyze the disease-causing mutations [derived from Online Mendelian Inheritance in Man (OMIM)] in successful drug targets. We found that >70% of the mutations are located far from the drug-binding sites (>12 Å), and most of the other mutations are unlikely to have adverse effects on drug binding, supporting the chemical strategy for combating genetic diseases.