Ischemic stroke is the 5th leading cause of death in the United States. Despite significant improvements in reperfusion therapies, stroke patients still suffer from significant neurocognitive deficits. This indicates an essential need to develop novel stroke treatment paradigms. Endogenous transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule drug delivery to the brain. One example of a transporter family that can be targeted to optimize blood-to-brain drug uptake are the organic anion transporting polypeptides (OATPs in humans; Oatps in rodents). Small molecule drugs that have neuroprotective properties are known substrates for these transporters and include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins). In this presentation, we review current knowledge on targeting of OATPs/Oatps for improvement of ischemic stroke treatment and provide state-of-the-art perspective on the rationale for considering BBB transport properties during discovery/development of novel stroke therapeutics.
Upon completion, participants will be able to describe blood-brain barrier (BBB) transport mechanisms that can facilitate delivery of small molecule therapeutics to the brain.
Upon completion, participants will be able to appreciate the need to consider drug transport mechanisms during preclinical development of small molecule therapeutics for treatment of neurological diseases.
Upon completion, participants will understand the need to evaluate regulatory mechanisms for BBB transporters.
Upon completion, participants will learn how intracellular signaling pathways can be targeted for the optimization of CNS drug delivery.