Researchers leading a worldwide clinical trial aimed at finding treatments for Alzheimer’s disease are modifying an arm of the trial to evaluate a combination of drugs targeting two brain proteins: amyloid and tau. The trial – known as the Tau Next Generation Trial (Tau NexGen) – originally was announced with a focus on drugs that target tau, but with increasing evidence that targeting amyloid can reduce biomarkers of Alzheimer’s disease, the trial’s leaders have revised the first arm to include an experimental therapy targeting amyloid as well.
Tau NexGen is part of the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by investigators at Washington University School of Medicine in St. Louis. The DIAN-TU is an international network of academic centers focused on finding therapies for Alzheimer’s disease by studying people who have rare, inherited mutations that almost certainly guarantee they will develop the disease at an early age.
“With growing evidence that removing amyloid plaques has biologically beneficial effects on amyloid and tau, we believe that targeting both Alzheimer’s disease pathologies — amyloid plaques and tau tangles — at the same time can provide the highest chance of success,” 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.
The DIAN-TU launched in 2012 as the first prevention trial platform for Alzheimer’s disease. A trial platform allows multiple treatments to be evaluated using a single master protocol. The first therapies evaluated on the DIAN-TU platform were designed to target the buildup of amyloid plaques in the brain. Such plaques are thought to contribute to problems with memory and thinking. With the initiation of the Tau NexGen trial, the DIAN-TU has extended its focus to another Alzheimer’s disease pathology, tau tangles, that has been closely linked to cognitive decline.
The Tau NexGen trial is designed with three arms. Each arm will evaluate an investigational drug that targets tau; each drug is designed to work in different ways.