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An ounce of prevention
PHOENIX—A group of Alzheimer's disease researchers is taking the road less traveled in this growing academic and commercial field, spearheading a dedicated effort to "launch the era of Alzheimer's prevention research"—before another generation of patients is lost.
The effort, called the Alzheimer's Prevention Initiative (API), aims to test potential Alzheimer's treatments and identify new biomarkers that could lead to earlier and more accurate diagnoses for Alzheimer's patients. Once that goal is achieved, the API then hopes to use these much-needed gains to eventually bring to market disease-delaying or prevention therapies.
The initiative initially grew out of efforts at the Banner Alzheimer's Institute (BAI), a nonprofit, collaborative research center in Phoenix that is working on evaluating pre-symptomatic Alzheimer's treatments and providing evidence to the U.S. Food and Drug Administration (FDA) to help assess the potential impact of these new therapies.
BAI's stated goals and mission—which it acknowledges are ambitious, but affirms are achievable—are threefold: to end Alzheimer's without losing a generation; to establish a new standard of care for patients and families; and to forge collaborative models in biomedical research. The institute's pursuit of the latter goal involves brain imaging studies, genomics and clinical trials.
The API 's current work on clinical trials has made headlines lately—notably, in the Washington Post and New York Times—putting the initiative and BAI on the map of cutting-edge Alzheimer's research.
Specifically, the API plans to launch two trials by 2012 that will evaluate pre-symptomatic Alzheimer's disease treatments and surrogate biomarker development. In both studies, the subjects will have completed genetic testing prior to participating in biomarker-driven trials of therapeutic agents aimed at delaying or preventing the onset of symptomatic Alzheimer's.
In one study, researchers will study 5,000 young to middle-aged adult relatives of a large, extended family in Antioquia, Colombia, about 1,000 of whom are estimated to carry a PS1 mutation known to cause early-onset Alzheimer's at about age 48. To date, more than 2,000 family members and 400 PS1 mutation carriers have had genetic testing, including more than 100 cognitively normal mutation carriers over the age of 40.
The other study will involve about 50,000 U.S. citizens aged 60 to 80 who carry two copies of the risk gene ApoE4. These individuals are at especially high risk for late-onset Alzheimer's and have an average age of dementia onset at about 68 years.
Leading this effort are Dr. Eric Reiman, executive director of BAI and the institute's lead researcher, and Dr. Pierre Tariot, associate director of BAI and director of the institute's Memory Disorders Center. Both men are internationally recognized for pioneering contributions to the fields of brain imaging, behavioral neuroscience and Alzheimer's disease research, and have each authored hundreds of scientific publications.
"We and others have shown how brain imaging and other biomarker techniques can be used to detect and track Alzheimer's before the onset of symptoms in people who are at risk for the disorder," says Reiman, who also serves as the clinical director of the Neurogenomics Division at the Translational Genomics Research Institute, or TGen. "Biomarkers have high value from a research standpoint, but until you embed them in clinical trials, you don't know if they will change in response to treatment. We need to have more humility about how these biomarkers work and embed them in clinical trials to help the field and develop the tools we need."
Tariot, who is also board-certified in internal medicine and geriatric psychiatry, points out that with the skyrocketing number of people living to older ages, there is an urgent need to find effective pre-symptomatic treatments and also help avert an overwhelming financial crisis. In addition, there are a number of suggested—but unproven—"healthy lifestyle" interventions that might reduce a person's chance of developing Alzheimer's symptoms that should be tested, he says.
Most notably, Tariot says, the trials will enable researchers to evaluate promising experimental therapies that have the potential to slow down, stop or prevent Alzheimer's from developing in the first place. While he is obviously unable to specify if any compounds in development have been selected or name companies that are working with the API, Tariot notes: "Consensus is mounting that these treatments may need to be started before the onset of symptoms for them to have their most pronounced benefit. As sufficient safety data is obtained, these new agents can then be studied in cognitively normal people who are at the highest imminent risk for symptomatic Alzheimer's, before the onset of symptoms."
Once regulatory agencies are able to support the use of surrogate endpoints to allow accelerated approval of pre-symptomatic Alzheimer's treatments, Reiman says, "This would help provide the incentives needed for sponsors to invest in many different prevention trials at the same time, and find one that works without losing a generation."
The API has many partners, including the National Institutes of Health, the Alzheimer's Disease Neuroimaging Initiative, the Alzheimer's Disease Cooperative Study, the Dominantly Inherited Alzheimer's Network, the Alzheimer's Association, Prevent Alzheimer's Disease 2010, ACT-AD, Leaders Engaged on Alzheimer's Disease and several other private foundations and advocacy groups—in addition to the FDA and other regulatory agencies.