By Kathleen Berger, Executive Producer for Science and Technology

An international clinical trial aimed at finding treatments for Alzheimer’s disease has recently expanded and changed to include an all new approach using investigational drugs. Randall Bateman, MD, professor of neurology at Washington University School of Medicine in St. Louis, is leading the global trial as principal investigator.

“Alzheimer’s disease has amyloid plaques and tau tangles. Those two things in the brain define Alzheimer’s disease. These new trials are targeting the tau tangles in the brain and trying to slow or prevent their onset so that we can slow or stop the progression of Alzheimer’s disease,” Bateman explained. “And then very recently, what’s changed is in addition to using a tau drug and a placebo to see if the tau drug can help slow down or stop Alzheimer’s, everyone is going to get an anti-amyloid drug. So this is also the first combination trial where we’re taking the one-two punch approach to Alzheimer’s, you have the plaques and the tangles. We’ll be attacking both of them in this trial.”

This combination drug approach is a result of increasing evidence that targeting the amyloid-beta protein can reduce biomarkers of Alzheimer’s disease. Amyloid-beta proteins clump together to form the sticky, toxic plaques scattered throughout the brain in Alzheimer’s.

“A lot of interest has been focused on tau recently because of the realization that tau seems to be the executer or the effecter of Alzheimer’s disease. Whereas we think amyloid plaques sets up the possibility to get Alzheimer’s, but then too you need the tau tangles to manifest the clinical aspects of the disease,” said Bateman. “Tau is the main part of tangles that form inside the neurons, the thinking cells of the brain. So this tau protein that makes up the tangles is a key target in Alzheimer’s disease treatment trials. Recent developments have allowed researchers to develop drugs which target tau to lower down the way that tau causes damage to the brain.”

Different arms of the clinical trial were already designed to introduce experimental drugs targeting the tau protein. That’s why the study is called the Tau NexGen trial. This is now the first Alzheimer’s prevention trial to target both amyloid and tau with two drugs at the same time. The trial will determine if the drug can slow, prevent or reverse tau tangles that build up in the brain.

Study participants will either receive an anti-tau drug or a placebo. But all study participants will receive drugs targeting amyloid-beta proteins to reduce or remove plaques. Study participants are 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.

Dr. Bateman is the director of the Dominantly Inherited Alzheimer Network Trials Unit. In addition to the combination drug approach, he explained how the trial is unique in another way.

“A very important part of this trial is something that’s quite different than trials before. It is that it enrolls two different populations of people who have the symptoms of Alzheimer’s disease. These are younger people who have mutations that cause Alzheimer’s disease at an early age. And it also enrolls people who are within 10 years of getting the symptoms of Alzheimer’s. So a prevention trial.”

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. That’s because the destructive molecular and cellular processes in the brain are similar in all types of the disease.