From the WashU Newsroom…
A worldwide clinical trial aimed at finding treatments for Alzheimer’s disease has expanded to include investigational drugs targeting a harmful form of the brain protein tau. The trial, known as the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) and led by Washington University School of Medicine in St. Louis, launched in 2012 as the first prevention trial for Alzheimer’s disease. Originally focused on amyloid-based therapies, it was funded by the National Institute on Aging (NIA) of the National Institutes of Health (NIH) in 2013.
Amyloid plaques in the brain are the first sign of Alzheimer’s disease. Such plaques start accumulating up to two decades before cognitive symptoms such as memory loss and confusion arise. For decades, Alzheimer’s researchers have searched for drugs to reduce or remove amyloid plaques as a way to treat the disease. Only recently have researchers begun developing drugs to target tau, which forms tangles in the brain that become detectable just before Alzheimer’s symptoms arise. The tangles are thought to be toxic to neurons, and their spread through the brain foretells the death of brain tissue and cognitive decline.
An experimental drug — an antibody called E2814 that recognizes the microtubule binding region (MTBR) of tau, developed by the pharmaceutical company Eisai Co. Ltd. — targets such tangles. It is the first of three planned tau drugs to be selected for evaluation in the DIAN-TU. The trial aims to determine whether such drugs reduce tau tangles and the damage caused by them, thereby slowing or stopping the progress of Alzheimer’s disease.
The addition of three new tau drug arms to the DIAN-TU is supported by grants expected to total $105 million from the NIA, $7 million each from the Alzheimer’s Association and GHR Foundation, and additional funding support from FBRI.
“As we’ve learned more about how Alzheimer’s develops, it has become clear that amyloid and tau both play critical roles in disease progression,” said principal investigator Randall J. Bateman, MD, director of DIAN-TU and the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University. “Our prior studies show that some anti-amyloid drugs have positive biological effects in the brain. We will now test multiple different anti-tau drugs to determine if and how targeting tau can slow or stop the progression of Alzheimer’s disease.”
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