Identifying and Validating New Drug Targets for Stroke and Beyond

Until very recently, drug discovery attrition rates have been increasing.1 This poor return on investment in biopharmaceutical research and development can be explained by scientific and extrascientific influences. Regulatory, payer, and commercial forces incentivized pharmaceutical companies to focus on common diseases and incremental improvements on existing mechanisms. The majority of resources within pharmaceutical companies have traditionally been focused on small-molecule drug discovery programs, reflecting a “hammer and a nail” mindset, with small-molecule chemistry as the hammer and the nail a classically defined “druggable” target. Rather than starting with a target based on strong human biological rationale, targets have been selected based on their ability to be “drugged” by a medicinal chemist. Compounding this problem has been an inadequate understanding of disease biology and an overreliance on animal models of human disease.