Tags

, , , , , ,

Margareta HammarlundLiesbeth de LangeRobert ThorneMargareta Hammarlund-Udenaes, Ph.D., is Professor of PKPD at Uppsala University, heading the Translational PKPD Group. Her research focuses on PK of BBB transport, nanodelivery, and translational aspects. She is chair of the 2014 Barriers of the CNS Gordon Conference.
Elizabeth C. M. de Lange, Ph.D., is Associate Professor and Head of the Target Site Equilibration Group of the Division of Pharmacology at the Leiden Academic Center of Drug Research (LACDR), at Leiden University, The Netherlands. She is program chair of the AAPS 2014 Annual Meeting and Exposition.
Robert G. Thorne, Ph.D., is Assistant Professor, Pharmaceutical Sciences, University of Wisconsin-Madison School of Pharmacy; Neuroscience, Cellular and Molecular Pathology, & Clinical Neuroengineering Training Programs. He is chair-elect of 2016 Barriers of the CNS Gordon Research Conference.

Many discussions are held in academia, the drug industry, and the clinic on how to understand drug delivery to the brain and how to solve the issues of treating diseases of the central nervous system (CNS). CNS diseases account for a large part of the disease burden and societal costs, with a proportionally lower research budget than other disease areas. We have seen several of the top ten pharma companies stopping or significantly reducing major efforts in the area due to the difficulties at hand. Thus the situation is crucial. One may wonder whether this is the new “antibiotics crisis”?

The blood-brain barrier (BBB), consisting of the endothelial capillary cells in the brain, has received more and more attention as a key player for drugs that reach or fail to reach the brain. With its 644 km (400 miles) of capillaries and 20 m2 of capillary surface area the BBB is the organ controlling the brain environment. The main players in the BBB are the tight junctions and the active efflux and influx transporters that together control the transport to and from the brain. Central nervous system (CNS) drug discovery has suffered from the methods that for many years have been used to measure “success” of delivery to the brain. These methods have included both nonspecifically bound drugs, as well as the free, pharmacologically active drug moiety, thereby blurring the picture of which new compounds actually are the best ones. The lack of animal models for CNS diseases is another huge problem. Added to the new issues CNS disease treatment is facing is the possible use of larger molecules that have even more problems in entering into the CNS. It is clear that the area needs a lot of attention and that collaboration and new knowledge is needed to understand and handle these issues going forward.

The new book Drug Delivery to the Brain: Physiological Concepts, Methodologies and Approaches is designed to provide state-of-the-art knowledge in the field by highlighting topics around several areas related to the theme. The 24 chapters written by experts in the field are divided into five sections, covering a wide range of topics from basic physiology through pharmacokinetic concepts and methods, industrial approaches including pharmacoeconomics considerations, to strategies for improved CNS drug delivery in disease. An appendix describes basic features of the brain. Each chapter includes a description of “Future Challenges”, as well as “Points for Discussion”, with questions intended to stimulate discussions.