Nigel Greig, PhD
National Institute on Aging
Dr. Nigel Greig was trained as a neuropharmacologist with a background in medicinal chemistry and physiology, and gained his PhD from the University of London (Department of Pharmacology, Royal College of Surgeons, England). Leaving Britain in 1982, he undertook postdoctoral training at the NIH. Thereafter, he worked in Pharma, and was then recruited to back to the NIH. He leads a multi-disciplinary research group (the Drug Design & Development Section within the Intramural Research Program of the National Institute on Aging (NIA), NIH) and cross-collaborates extensively with NIA, NIH, academic and Pharma related groups across the world.
He focuses to design, synthesize, and develop novel agents against pivotal targets in age prevalent diseases, with a CNS emphasis. Novel compounds are synthesized as pharmacologic probes to target biological mechanisms and, for those that appear involved in disease progression, early integration of ‘drug-like’ features provides experimental drugs that are evaluated in cellular and animal disease models and are then translated, in line with regulatory requirements, into human clinical trials to test new hypotheses. Likewise, approved and well-tolerated drugs that target mechanisms of potential relevance across diseases are repurposed to new disorders that lack effective therapeutics. This strategy allows Nigel and colleagues to validate/invalidate disease targets, and, as key elements of clinical drug development, to patent and out-license new drug candidates to support their clinical development to public use. These patents belong to NIH and, hence, the US Government and nation.
As examples of ongoing work, Nigel’s research resulted in the development of the drugs Phenserine and Posiphen (Buntanetap) and GLP-1 receptor agonists (Exenatide, PT320) as new treatments for neurodegenerative disorders that are now in multiple clinical trials (including Parkinson’s and Alzheimer’s disease (PD, AD)). Preclinically, the Greig NIA/NIH laboratory with collaborators developed the first amyloid precursor protein/amyloid-b lowering agents to enter human trials, selective acetyl- and butyryl-cholinesterase inhibitors (Bisnorcymserine) that, likewise, have entered clinical trials, p53 inactivating agents and novel thalidomide analogs lacking classical cereblon binding. To undertake this work, an experienced multidisciplinary collaborative team covers preclinical medicinal chemistry and cellular/in vivo pharmacology to successfully test focused scientific hypotheses, and integrates this with neurological clinical trial design, biomarker evaluation, clinical pharmacology and FDA regulatory requirements – to move novel as well as repurposed drugs from conception into clinical trials. This team includes Nigel, his research section, NIA and NIH colleagues, and a group of collaborative basic and clinical scientists from academia and Pharma/Biotech from across the globe. Key focuses of Nigel’s work are to provide knowledge gained from the group’s research to the scientific community to advance public health, and to help train the next generation of scientists.