Dementia Drug Candidate in Preclinical Tests

Linda Van Eldik. (Mark Cornelison, Univ of Kentucky)

7 Oct. 2019. A study is underway of a new treatment approach for dementia that targets inflammation and microscopic bleeding in the brain that can accompany Alzheimer’s disease. The research at University of Kentucky in Lexington is funded by a five-year, $2.8 million grant from National Institute on Aging, part of National Institutes of Health.

A team led by Linda Van Eldik, director of the Sanders-Brown Center on Aging at UK, seeks to better understand the role of inflammation of neurons in the brain, found in people with Alzheimer’s disease as well as vascular cognitive impairment and dementia, or VCID, a related disorder. VCID is considered the second-most common cause of dementia after Alzheimer’s disease, and can occur at the same time.

“Alzheimer’s disease and VCID pathology are frequently found together in the brains of older people,” says Van Eldik in a university statement, “but little is known about how these two diseases interact and drive progression of dementia symptoms, though the evidence so far suggests it’s additive.”

Van Eldik and colleagues are testing the hypothesis that the inflammation of neurons found in people with Alzheimer’s disease and VCID result from signals from the protein p38alpha-MAPK. The researchers cite earlier studies showing evidence that p38alpha-MAPK is associated with early stages of Alzheimer’s disease, as well as chronic neuron inflammation and degeneration. And the group believes the presence of bleeding in the brain adds to the inflammation.

The study team is assessing a drug candidate developed recently at UK code-named MW150, in lab mice induced with brain bleeding similar to VCID. MW150 is a small-molecule or low molecular weight compound that can cross the blood-brain barrier, designed to limit p38alpha-MAPK proteins in the brain. The team is evaluating MW150 as a preventive treatment for VCID, including the minimum dose to prevent the condition, as well as a therapy for older mice already with VCID like that found in patients with Alzheimer’s disease. In addition, the researchers plan to document the drug’s mechanisms of action against p38alpha-MAPK.

Results from these preclinical tests are expected to supplement an early-stage clinical trial of a related compound code-named MW151. In February, UK received a two year, $1.4 award from National Institute on Aging for the clinical study of MW151’s safety and dosage levels.

“Given the urgency of the unmet medical need, particularly here in Kentucky where vascular disease is so prevalent,” adds Van Eldik, “a new treatment either as a stand-alone therapy or as part of a multi-drug cocktail is a critical tool to fight an illness that threatens to overwhelm patients and their families physically, emotionally and financially.”

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