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$4 million grant expands major study to find Alzheimer’s prevention treatments

Investigators will accelerate drug testing, develop new diagnostic measures

by Tamara BhandariJune 21, 2016

Judy Martin Finch

Washington University School of Medicine in St. Louis has received a $4.3 million award from the Alzheimer’s Association to expand a major international clinical trial evaluating whether drugs can prevent Alzheimer’s disease in patients genetically predisposed to develop the devastating disease at a young age.

The funding will accelerate testing of new drugs against early-onset Alzheimer’s and builds on the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) study, which is led by Washington University. The DIAN-TU, which got underway in 2012, is the first trial aimed at identifying drugs to prevent or slow Alzheimer’s in people who are certain to develop the disease but do not yet show symptoms.

The new phase of the trial is known as the DIAN-TU Next Generation Prevention Trial (NexGen). As part of the trial’s expansion, multiple sites worldwide will be added to the study.

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“New funding for the DIAN-TU NexGen is helping us move forward with the trial and is critical to finding a way to slow or stop the progression of Alzheimer’s,” said the DIAN-TU program director and principal investigator, Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University. “We hope to be able to intervene before symptoms of the disease, such as memory loss and cognitive decline, become apparent. The expansion of the trial will let us start quickly with novel trial approaches, which will test additional drug targets with advanced methods.”

The DIAN-TU and the DIAN-TU NexGen trials grew out of the Dominantly Inherited Alzheimer Network (DIAN), an international research network led by Washington University and involving 15 research institutes in the United States, Australia, Europe, Asia and South America. It was established in 2008 with funds from the National Institute on Aging of the National Institutes of Health (NIH) and the Alzheimer’s Association to investigate Alzheimer’s caused by rare, inherited genetic mutations that all but guarantee that people will develop the disease, usually in their 30s, 40s or 50s.

In families that carry dominant mutations for Alzheimer’s, doctors can predict who will develop the disease and at what age. This allows researchers to look for brain changes – long before symptoms appear – in people who carry such mutations, compared with their relatives who don’t. In 2012, the network’s researchers reported they had detected changes to brain chemistry two decades before the onset of Alzheimer’s symptoms.

In addition to expanding drug testing, DIAN NexGen will add other aspects to the project. Tammie Benzinger, MD, PhD, an associate professor of radiology and of neurological surgery, leads a section of the project devoted to implementation of a tau biomarker using positron emission tomography (PET) scanning. Tangles of tau protein mark the brains of people with Alzheimer’s. “This grant will allow for the development of technology to study tau tangles in people and evaluate tau as a biomarker for disease progression and effectiveness of treatment,” Benzinger said.

The grant also will provide support for more frequent and at-home cognitive testing. Cognitive testing at home will reduce some of the time burden on participants, who typically make multiyear commitments to the DIAN project. Cognitive testing at two-month, rather than six-month, intervals is expected to increase the reliability of tests for detecting subtle cognitive changes, according to Jason Hassenstab, PhD, an assistant professor of neurology and the leader of the cognitive testing portion.

A second annual conference in July for families with dominantly inherited Alzheimer’s also will be funded by the grant. The first annual conference, held in July 2015, allowed study participants and their families to share their perspectives with researchers and meet other people with the same genetic disposition. Such meetings encourage ongoing participation and engagement.

“We ask so much of the participants in terms of time and energy,” said Eric McDade, DO, an assistant professor of neurology and associate director of the DIAN-TU study. “This conference gives us a chance to get feedback from them. And seeing the people who are directly affected is a great motivator for us to go back to work trying to cure this terrible disease.”

Since dominant mutations for Alzheimer’s are so rare, finding the 230 participants needed for the NexGen studies requires an international effort. To include additional patients, the program likely will be expanded to additional countries including Germany, Argentina, Japan, South Korea, Denmark, Switzerland and possibly others.

Findings from the DIAN trials also may aid treatment for the 5 million Americans living with the more common form of Alzheimer’s, which affects people later in life. The processes that lead to memory loss and cognitive impairment are thought to be the same whether the disease is caused by a dominant mutation or by the complex combination of genetics and environment that causes most Alzheimer’s cases.

The Alzheimer’s Association funding for the DIAN-TU NexGen is made possible by donations to the Alzheimer’s Association from St. Louis-based financial services firm Edward Jones; Washington University alumnus and philanthropist John Beuerlein and his wife, Crystal, of St. Louis; and Mary Barton Smith, of Portola Valley, Calif.

In addition to the Alzheimer’s Association and the NIH, the DIAN and DIAN-TU also receive support from a pharma consortium composed of Amgen, AstraZeneca, Biogen, Eisai, Forum Pharmaceuticals, Janssen Pharmaceuticals, Lilly, Pfizer, Roche and Sanofi. Elan Pharmaceuticals, Mithridion and Novartis have provided support for DIAN and DIAN-TU in the past. The German Center for Neurodegenerative Diseases (DZNE) completely supports German DIAN sites.

Washington University School of Medicine‘s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.