$29 Million NIH Grant Will Fund Clinical Trial for Dementia with Lewy Bodies

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University of Miami Miller School of Medicine neurologist James Galvin, M.D., M.P.H., who studies Alzheimer’s disease and dementia with Lewy bodies (DLB), will be one of the principal investigators on a $29 million National Institutes of Health grant to test whether a new drug is safe and effective for patients with DLB. The drug, called CT1812, is being developed by co-awardee Cognition Therapeutics to treat both DLB and Alzheimer’s disease.

James E. Galvin, M.D., M.P.H.

“When CT1812 was developed as a small molecule that modulates a receptor in the brain called sigma-2, they found it prevents the binding of the amyloid protein responsible for the major pathology in the brains of people with Alzheimer’s disease and blocks its toxic effects,” said Dr. Galvin, professor of neurology and director of the Comprehensive Center for Brain Health. “But they also found CT1812 has a similar effect on alpha-synuclein protein, the building block for Lewy bodies depositing in the brains of people with DLB.”

Alzheimer’s disease and DLB share many common features and have similar disease mechanisms. In Alzheimer’s, the amyloid protein aggregates to create the senile plaques. In DLB, alpha-synuclein protein similarly aggregate to form Lewy bodies. Researchers believe CT1812 works by selectively displacing alpha-synuclein and amyloid from the sigma-2 receptor, increasing the ability of the brain to clear these toxic proteins and protecting against the loss of synapses. This could make the drug particularly important for DLB patients, as their brains often accumulate both Lewy bodies and amyloid plaques.

According to the Lewy Body Dementia Association, there are around 1.4 million people in the United States with DLB, making it the second-most prevalent cause of dementia after Alzheimer’s. Unfortunately, there are no approved drugs for the disease, forcing clinicians to prescribe off-label treatments to manage symptoms.

“There's nothing specific we can offer patients, other than using symptomatic medicines taken from other fields,” said Dr. Galvin. “We borrow medicines from Alzheimer's to treat cognitive symptoms, from Parkinson's to treat motor symptoms, from narcolepsy to treat attention deficits and from psychiatry to treat behavioral symptoms.”

The NIH grant, one of the largest ever awarded to investigate DLB, will fund a multi-center phase 2 clinical trial in 120 DLB patients, which will primarily investigate whether CT1812 is safe. Dr. Galvin and Cognition Therapeutics will oversee the trial’s design, implementation, data analysis and other important tasks. Dr. Galvin will also work with the Lewy Body Dementia Association, which will help recruit patients and coordinate with trial sites through its Research Center of Excellence Program. Dr. Galvin leads University of Miami’s Center of Excellence.

If the drug succeeds in phase 2, it could proceed to a larger phase 3 trial, which will focus on efficacy in a larger sample to determine if it’s suitable for approval by the Food and Drug Administration.

“There are currently no medicines that address the underlying disease process for DLB,” said Dr. Galvin, noting that this is the first drug that could potentially accomplish that. “If we can get CT1812 through a successful phase 3 clinical trial and gain FDA approval, that would be a huge advance and could significantly improve the clinical care and quality of life for patients and their families living with DLB.”