Applying genetics in inflammatory disease drug discovery

• Published in: Drug discovery today 2015-10, Vol.20 (10), p.1176-1181
• Main Authors: Folkersen, Lasse, Biswas, Shameek, Frederiksen, Klaus Stensgaard, Keller, Pernille, Fox, Brian, Fleckner, Jan
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Drug Design; Drug Discovery - methods; Genetic Variation; Genome-Wide Association Study - methods; Humans; Inflammation - drug therapy; Inflammation - genetics; Molecular Targeted Therapy
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2015.05.012

•Genetic evidence may illustrate causal links to disease.•Connecting a genetic marker to a drug target candidate is possible, but not trivial.•Practical implementation of genetics in autoimmune disease drug discovery is shown.•Challenges and opportunities of genetic methods are discussed. Recent groundbreaking work in genetics has identified thousands of small-effect genetic variants throughout the genome that are associated with almost all major diseases. These genome-wide association studies (GWAS) are often proposed as a source of future medical breakthroughs. However, with several notable exceptions, the journey from a small-effect genetic variant to a functional drug has proven arduous, and few examples of actual contributions to drug discovery exist. Here, we discuss novel approaches of overcoming this hurdle by using instead public genetics resources as a pragmatic guide alongside existing drug discovery methods. Our aim is to evaluate human genetic confidence as a rationale for drug target selection.