Imaging in Neuroscience Drug Discovery

Richard Hargreaves
Worldwide Head Basic Neuroscience Research, Merck and Co. Inc. West Point PA 19486

Imaging is a key area of ‘translational research’ that provides a unique bridge from the laboratory to the clinic as the same techniques and technologies can applied across the various phases of drug development. Neuroimaging is now central to research and drug development in the neurosciences since it can be used to detect the pharmacological and physiological consequences of drug action within the living brain. Today neuroimaging is used primarily as a "biomarker" to help optimize our decision-making processes. Neuroimaging tools and technologies can be used to select drug candidates, confirm they engage their targets, link occupancy to biology and then, in a translational fashion, be used to help design the best clinical studies that truly test our therapeutic hypotheses. Conceptually, neuroimaging in drug discovery and development can be divided into three categories that are clearly inter-related.  1) Neuroreceptor mapping to examine drug occupancy characteristics, the involvement of specific neurotransmitter systems in CNS diseases and mechanisms of action; 2) Functional mapping  to provide pharmacodynamic evidence of central activity, “CNS fingerprinting” of the neuroanatomy of drug effects and disease drug interactions. 3) Structural and spectroscopic imaging to examine morphological changes and their consequences. Positron Emission Tomography (PET) and Magnetic Resonance (MR) currently dominate the methodologies that are used for neuroimaging. Each technique, whilst powerful in its own right, has optimal value for understanding the pathophysiological characteristics of CNS diseases, their diagnosis and potential treatment outcomes when combined together due to the complimentary nature of the information they provide. Neuroimaging today is all about the need to identify the best molecules, doses and hypotheses to advance into later stage long term extensive clinical trials that can often be confounded by high placebo response rates. Better decision making in early development allows us to focus our resources on the drug candidates and therapeutic hypotheses that have the highest probability of success so that we can bring medical advances to our customers as quickly as possible.

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