Drug Candidate Designed by NIH Scientists Reduced Brain Inflammation, Protected Against Cognitive Decline in Alzheimer’s Mouse Model
WHAT
An anti-inflammatory drug candidate, known as 3,6’-dithiopomalidomide (DP), designed by researchers at the National Institute on Aging (NIA), protected lab mice against cognitive decline by reducing brain inflammation. An international research team led by the NIA scientists published their findings in Alzheimer’s and Dementia: The Journal of the Alzheimer's Association. NIA is part of the National Institutes of Health.
Study Lead Author, Nigel Greig, right
The study results provide new evidence that brain inflammation — which occurs decades before Alzheimer’s symptoms are noticeable — is a key neuropathological pathway of interest in efforts to find potential treatments for Alzheimer’s.
To investigate whether brain inflammation was directly involved in cognitive loss, researchers used a mouse model specially designed to produce up to five times the normal levels of beta-amyloid plaques. These plaques are a hallmark sign of Alzheimer’s and are thought to contribute to a destructive inflammatory response in the brain. After four months of treatment with DP, the mice showed reduced brain inflammation and neuron death, and they had more neural connections in the brain areas responsible for memory and attention. DP-treated mice also showed improvement in behavioral laboratory tasks that test spatial and working memory as well as anxiety behaviors and motor function, results the researchers see as protective against cognitive impairment.
WHO
Study Lead Author:
- Nigel Greig, Ph.D., chief, Drug Design and Development Section, NIA Intramural Research Program
Broader Perspectives:
- Richard J. Hodes, M.D., director, NIA
- Luigi Ferrucci, M.D., scientific director, NIA
The research was funded in part by the NIH Intramural Research Program grant ZIAAG000994 and NIA grant R56AG057028.
NIA leads NIH’s systematic planning, development, and implementation of research milestones to achieve the goal of effectively treating and preventing Alzheimer’s and related dementias. These activities relate to NIA’s AD+ADRD Research Implementation Milestone 6.D, “Initiate drug discovery efforts to develop novel therapeutic agents against at least six novel therapeutic targets….”
About the National Institute on Aging (NIA): NIA leads the U.S. federal government effort to conduct and support research on aging and the health and well-being of older people. Learn more about age-related cognitive change and neurodegenerative diseases via NIA’s Alzheimer's and related Dementias Education and Referral (ADEAR) Center website. Visit the main NIA website for information about a range of aging topics, in English and Spanish, and stay connected.
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Reference:
Lecca D, et al. Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis. Alzheimer’s & Dementia. 2022. doi:10.1002/alz.12610.