By Kathleen Berger, Executive Producer for Science & Technology
An international 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. Originally focused on amyloid-based therapies, the trial launched with funding from 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. Beta amyloid proteins clump together to form the sticky, toxic plaques scattered throughout the brain in Alzheimer’s. The plaques start accumulating up to two decades before cognitive symptoms such as memory loss and confusion arise. The beta amyloid protein is a target for emerging drug therapies to reduce or remove plaques to treat the disease, but there is also another protein that defines Alzheimer’s disease, called tau.
“A lot of interest has been focused on tau recently because of the realization that tau seems to be the effecter or executor of Alzheimer’s Disease,” said Randall Bateman, MD, professor of neurology at Washington University School of Medicine in St. Louis. “You need the tau tangles to manifest the clinical aspects of the disease.”
Dr. Bateman has a laboratory dedicated to the causes, diagnosis and future treatments of Alzheimer’s disease. He is now leading a global effort to advance new drugs targeting the tau protein. Bateman is the director of the Dominantly Inherited Alzheimer Network Trials Unit and he’s the principal investigator for this global network’s Phase 2 clinical trials, called the Tau Next Generation Trials, introducing new drugs targeting tau proteins.
“Tau is the main part of tangles that form inside the neurons of thinking cells of the brain,” he said. “So the tau protein that makes up the tangles in a key target in Alzheimer’s disease treatment trials.”
The clinical trials are designed for patients and family members of dominantly inherited Alzheimer’s disease. This is a rare form of Alzheimer’s from genetic mutations that people inherit from their parents. The trials will investigate what Bateman calls “anti-tau tangle drugs”. They will focus on three different drugs with clinical trials this year, then next year and the third clinical trial expected in 2023.
The research team will choose from two classes of tau drugs that act in different ways. This includes small molecule drugs that inhibit tau aggregation and genetic treatments that reduce the production of the tau protein. The first of the three experimental drugs is now used in the first clinical trial enrolling more than 200 people.
“This first one is this anti-tau antibody,” said Bateman. “It is a special protein, an antibody, that’s been specifically designed to target a very specific form of tau, the kind of tau that we believe has a role in tau toxicity and aggregation.”
The trial will determine if the drug can slow, prevent or reverse tau tangles in the brain.
Although the trial focuses on people with rare mutations, drugs that are successful in this population would be promising candidates for preventing or treating late-onset, or sporadic, Alzheimer’s disease that occurs more commonly in older adults. The destructive molecular and cellular processes in the brain are similar in all types of the disease.