Drug Discovery in CNS: Finding a Target for What?

In the last decades, not much progress has been made in finding new treatments for CNS diseases. The well-established concepts of target identification and validation are at the core for drug discovery and development programs. It is argued that this is the most critical step in finding new treatments. Drug target finding has been pursued using genome-wide association study (GWAS) methods (see ? Chap. 7), but this has not been proven successful for CNS diseases yet. Various potential issues with the GWAS approach are listed and may dampen the validity of using GWAS for target finding. Two recent alternative methods for target finding are discussed. One approach is related to the research domain criteria (RDoC) initiative (see ? Chap. 19) in which different functional domains are connected with neurodevelopmental and biological mechanisms in a matrix format. Thereby, drug targets could be identified for these brain functions. Another approach mentioned here is based on the “diseasome” (network medicine), which is a data-driven approach using molecular biology and genetic information to find treatment-based mechanism. Although these two approaches may seem promising, no promising clinical treatments are available yet. Target identification still remains the most important and challenging step in drug discovery and development for CNS diseases.