Interest in the development of drugs for rare diseases — orphan drugs — has substantially increased in recent years, with the aid of regulatory and economic incentives. In their Perspective, members of the Committee for Orphan Medicinal Products of the European Medicines Agency discuss outcomes from the first decade of such regulatory incentives in Europe, and consider key issues for the future. Meanwhile, our Reviews this month cover a diverse range of topics. Exploiting synthetic lethality — in which a combination of mutations in two genes results in cell death — is emerging as a promising anticancer strategy, as cancer cells characteristically possess genetic mutations that are not present in normal cells, and so it is possible to selectively kill cancer cells by mimicking the effects of synthetic lethal mutations with a therapeutic agent. Chan and Giaccia review strategies to identify synthetic lethal interactions and present case studies of anticancer agents that act by inducing synthetic lethality. Understanding the role of genetic mutations that are implicated in Parkinson's disease pathogenesis could also lead to more effective therapies. This is discussed by Meissner and colleagues, who review emerging targets and agents and consider key issues facing future Parkinson's disease drug development, including the identification of reliable biomarkers for use as clinical trial end points. Inflammation is now recognized as an important contributor to atherosclerosis, and monitoring various inflammatory biomarkers could be useful in making clinical decisions. Charo and Taub discuss recent advances in the use of such biomarkers and imaging techniques in cardiovascular disease and highlight novel anti-inflammatory targets and associated agents that are under investigation.
