Washington University School of Medicine in St. Louis has received nearly $4.2 million from the Alzheimer's Association to accelerate the launch of the first clinical trials to prevent the symptoms of Alzheimer's disease.
The award is the largest research grant in the history of the 32-year-old association.
Randall Bateman, MD, principal investigator of the grant and director of the Dominantly Inherited Alzheimer's Network (DIAN) Therapeutic Trials Unit (TTU) at Washington University, will lead the trials, which will determine if the disease can be halted or delayed before problems in memory and other brain functions become apparent.
The research will be conducted through the Dominantly Inherited Alzheimer's Network, an international research partnership focused on understanding inherited forms of Alzheimer's. DIAN is headed by John C. Morris, MD, Harvey A. and Dorismae Hacker Friedman Professor of Neurology at Washington University School of Medicine. Bateman and Morris treat patients at Barnes-Jewish Hospital.
"We're grateful for the Alzheimer's Association's support for these trials and for the generous support it has given us throughout the long journey that has led to them," Morris says. "We've been working for years to find a way to treat Alzheimer's disease before patients develop dementia, and it's very exciting to be making plans to start the first of such trials later this year."
"This project has the potential to dramatically accelerate the pace of treatment and prevention strategies for Alzheimer's," said William Thies, PhD, the Alzheimer's Association's chief medical and scientific officer. "We are convinced that helping to rapidly launch the DIAN-Therapeutic Trials Unit will accelerate discovery of therapies that will change the course of the Alzheimer's disease process and delay or stop the disease."
Families enrolled in the DIAN study have inherited forms of Alzheimer's that cause dementia at a much earlier age than the more common sporadic forms of the disease. Scientists have identified mutations in three genes that cause inherited Alzheimer's. An individual who inherits one of these mutations typically develops symptoms of the disease at approximately the same young age as his or her parents.
Last July, DIAN researchers announced at the Alzheimer's Association International Conference that they could detect biological markers of presymptomatic disease in DIAN participants up to 20 years before the patients were expected to develop memory problems.
"We want to prevent damage and loss of brain cells by intervening early in the disease process — even before outward symptoms are evident, because by then it may be too late," says Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor in Neurology and director of the DIAN Therapeutic Trials Unit, which will conduct the new trial.
With the advice of a newly formed consortium of 10 pharmaceutical companies, DIAN researchers under Bateman's leadership will select what they believe to be promising pharmaceuticals for the trials. They plan to give the drugs to family members who have an early-onset Alzheimer's gene and biological markers of disease but do not yet have symptoms of dementia. The goal will be to see if treatment can reduce the biological markers, potentially delaying or preventing the onset of symptoms.
"Experimental treatments have risks, so to treat patients before symptoms occur, we must be sure that we have a firm grasp on who will develop Alzheimer's dementia," says Morris, who also is director of the Charles F. and Joanne Knight Alzheimer's Disease Research Center at Washington University. "If we can find a way to delay or prevent dementia in DIAN participants, that would be a tremendous success story and very helpful in our efforts to treat the much more common sporadic forms of the illness."
The pharmaceutical consortium advising DIAN researchers is comprised of the Janssen Alzheimer Immunotherapy – Pfizer Alliance, Biogen Idec, Elan, Eli Lilly, Genentech, Hoffman La-Roche, Mithridion, Novartis, Pfizer and Sanofi-Aventis.
"The DIAN Pharma Consortium is an indicator of how important the DIAN trials are," Bateman says. "It's amazing that 10 pharmaceutical companies that are normally competitors have agreed to work together to help provide advice about DIAN trials design."
The DIAN Therapeutic Trials Unit has launched the DIAN expanded registry for interested patients, family members, doctors and researchers. For more information or to register for potential participation in the trials, go to http://www.DIANXR.org.
In addition to Washington University, the other institutions involved in DIAN are Harvard University, Massachusetts General Hospital, Brown University, Columbia University, Indiana University, the University of California, Los Angeles, the University College of London's Institute of Neurology at Queen's Square and a consortium of the universities of Brisbane, Perth and Sydney in Australia.
The Dominantly Inherited Alzheimer's Network is supported by funding from the National Institute on Aging. The Dominantly Inherited Alzheimer's Network Therapeutic Trials Unit is supported by funding from an anonymous foundation, the DIAN Pharma Consortium and the Alzheimer's Association.
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.