The first two patients with early or asymptomatic Alzheimer's disease will be screened this week for a novel national clinical trial led by UC San Francisco.
This is the first large-scale trial to test a combination of therapies for the most common form of Alzheimer's. The study will test drugs that target both amyloid and tau - two proteins that play key roles in the disease. Researchers plan to enroll up to 825 participants across multiple U.S. sites.
This trial will test whether treating both amyloid and tau at the earliest signs of tau buildup will work better than targeting either protein alone.
Adam Boxer, MD, PhD
The trial is also the first of its kind to include patients who have no symptoms but show biological signs of Alzheimer's. In the trial, all participants will receive at least one active treatment. Researchers will add drugs from different, sometimes competing, companies over time.
Currently, the only FDA-approved drugs for Alzheimer's target amyloid, which forms plaques in the brain that disrupt communication between nerve cells. Tau forms the toxic tangles in the brain that ultimately lead to cognitive decline.
"Many people have amyloid plaques in their brain for over a decade, but don't develop symptoms until tau starts to accumulate," said co-principal investigator Adam Boxer , MD, PhD, of the UCSF Fein Memory and Aging Center . Symptoms usually begin after tau starts to accumulate.
"This trial will test whether treating both amyloid and tau at the earliest signs of tau buildup will work better than targeting either protein alone," Boxer said.
Funded by the National Institutes of Health (R01AG078457), the Alzheimer's Tau Platform (ATP) trial is designed to speed the development of new, tau-targeting therapies while reducing the cost and burden for patients. It will also create a wealth of data and biological samples for researchers to better understand the disease.
For the first six months, participants will receive either a placebo or donanemab, an FDA-approved drug that can slow the progression of early Alzheimer's by targeting amyloid. This will be followed by a tau drug alone or combined with donanemab for two years. The first tau therapy to be tested is AADvac1, a drug that trains the immune system to attack the harmful tau protein.
The trial is co-led by Keith Johnson, MD, of the Massachusetts General Hospital and Harvard Medical School. It is open to people aged 50 to 80 who have mild cognitive impairment or who have no symptoms. Both groups must undergo screening for amyloid and tau, consistent with Alzheimer's, to qualify. Patients must be willing to undergo regular testing, including brain imaging.
