The Drug Design and Development Section (DDDS) is focused to identify drugs that improve brain function and/or forestall the neurodegenerative process in age-related neurodegenerative disorders. Data arising from studies on neurodegenerative and neuroprotective signaling pathways are used to identify potential drug targets. Candidate drugs are designed and synthesized and then screened for efficacy in cell culture and animal models, and the most effective compounds are moved through preclinical studies to clinical trials. Novel as well as re-positioned drugs that mitigate neurodegenerative processes are currently in clinical trials, and novel compounds to dampen neuroinflammatory cascades involved in acute and chronic neurodegenerative disorders are at various preclinical stages of development.
Nigel Greig was trained as a pharmacologist with a background in medicinal chemistry and physiology, and gained his Ph.D. from the University of London; specifically, from the Pharmacology Department of the Royal College of Surgeons, England. The research portion of his Ph.D. was undertaken next door within the Cancer Chemotherapy Department of the Imperial Cancer Research Fund (ICRF) under the mentorship of Prof. Kurt Hellmann – who took the drugs razoxane and dexrazoxane (Zinecard, Cardioxane) from concept to the clinic.
Leaving the ICRF and Britain in 1982, Nigel joined the Laboratory of Neuroscience within the Intramural Research Program (IRP), National Institute on Aging (NIA), NIH, as a Post-doc in the US. His initial studies focused on optimizing the delivery to and action of drugs within the brain. This resulted in the development of drug candidates for the treatment of brain tumors and cancers of the breast, lymphatics and ovaries, as well as technology for the delivery of neuropeptides, antisense oligonucleotides and proteins to the brain. Leaving NIA in 1989, Nigel was one of the initial scientists in the California-based Alzheimer biotechnology company, Athena Neurosciences, which later became a key part of Elan Pharmaceuticals and is now part of Perrigo. Athena was launched on technology deriving from Nigel's NIA research as well as separate technology from the Selkoe Laboratory, Harvard University.
Returning to NIA as a tenured scientist in 1992, Nigel's research has evolved into his present interest, the design and development of drugs for the treatment of degenerative disorders prevalent in aging, with particular emphasis on chronic (Alzheimer's and Parkinson's disease) and acute (traumatic brain injury and ischemic stroke) neurodegenerative disorders, and type 2 diabetes. He heads the Drug Design & Development Section within the Translational Gerontology Branch, IRP, NIA, NIH, located in Baltimore, MD, USA.
Nigel's program combines cellular and in vivo pharmacology with neurobiology and medicinal chemistry to design and develop novel experimental drugs against rate-limiting steps involved in the pathophysiology of diseases associated with aging. In extensive studies with a core of long-time, close collaborators from academia within and outside the US, Pharma and NIH - together - they have successfully moved multiple experimental drugs from concept through preclinical studies and into human clinical trials (Phenserine, Posiphen (ANVS 401, ANVS 405), Bisnorcymserine (ANVS 301), Exendin-4 (Exenatide, PT320). These, as well as new preclinical drugs, have been licensed from NIA, NIH, and collaborating institutions into both new startup as well as existing companies to support their development to improve public health.
Publications/patents are available via the links:
- Lecca D, Jung YJ, Scerba MT, Hwang I, Kim YK, Kim S, Modrow S, Tweedie D, Hsueh SC, Liu D, Luo W, Glotfelty E, Li Y, Wang JY, Luo Y, Hoffer BJ, Kim DS, McDevitt RA, Greig NH. Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis. Alzheimers Dement. 2022.
- Lin CT, Lecca D, Yang LY, Luo W, Scerba MT, Tweedie D, Huang PS, Jung YJ, Kim DS, Yang CH, Hoffer BJ, Wang JY, Greig NH. 3,6'-dithiopomalidomide reduces neural loss, inflammation, behavioral deficits in brain injury and microglial activation. Elife. 2020;9.
- Glotfelty EJ, Olson L, Karlsson TE, Li Y, Greig NH. Glucagon-like peptide-1 (GLP-1)-based receptor agonists as a treatment for Parkinson's disease. Expert Opin Investig Drugs. 2020;29(6):595-602.
- Lecca D, Bader M, Tweedie D, Hoffman AF, Jung YJ, Hsueh SC, Hoffer BJ, Becker RE, Pick CG, Lupica CR, Greig NH. (-)-Phenserine and the prevention of pre-programmed cell death and neuroinflammation in mild traumatic brain injury and Alzheimer's disease challenged mice. Neurobiol Dis. 2019;130:104528.
- Athauda D, Gulyani S, Karnati HK, Li Y, Tweedie D, Mustapic M, Chawla S, Chowdhury K, Skene SS, Greig NH, Kapogiannis D, Foltynie T. Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial. JAMA Neurol. 2019;76(4):420-429.
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This page was last updated on Monday, July 25, 2022