From Nature:

"Aisen foresees a future — maybe just a decade or so down the line — in which much of the burden of Alzheimer’s disease might actually be prevented. “We’re heading towards screening people from middle age on with blood tests, and treating those who show amyloid abnormalities with drugs that reduce the generation of amyloid plaques,” he says. “I am optimistic.”

A lot needs to go right for this hopeful view to become reality. Large clinical trials will have to show that these therapies work, and amyloid-clearing drugs will have to be proven to be safe and affordable. After decades of setbacks and failed clinical trials, some dementia researchers prefer to express caution. “The field is taking tremendous risks by engaging in studies that can cost billions of dollars,” says neurologist David Knopman at the Mayo Clinic in Rochester, Minnesota.

It will take a while for answers to emerge. Some trials of Alzheimer’s disease prevention are just getting started, and some ongoing ones could stretch into the next decade."

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Washington University School of Medicine in St. Louis is launching an international clinical trial aimed at preventing Alzheimer’s disease in people genetically destined to develop the illness at a young age. Unlike most other Alzheimer’s prevention trials, this one will enroll people before the disease has taken hold – up to 25 years before the expected onset of dementia.

Called the Primary Prevention Trial, the new study will investigate whether gantenerumab — an investigational antibody under development for Alzheimer’s disease by Roche and Genentech, a member of the Roche Group — can clear a key Alzheimer’s protein called amyloid beta, and slow or stop the disease. Amyloid is the chief component of plaques that dot the brains of people with the disease. Many scientists suspect the disease originates from the buildup of amyloid plaques in the brain that start to develop up to two decades before symptoms of dementia begin.

“Overwhelming evidence suggests that the most effective way to slow or stop amyloid beta is to prevent it from building up in the first place, but most of the drugs targeted to this protein have been tested in people who already have at least some early signs of the disease, such as memory loss – when the disease is far enough along that reducing amyloid alone isn’t likely to stop it,” said Eric McDade, DO, an associate professor of neurology and the trial’s principal investigator. “We’ll be recruiting participants as young as 18. In many ways, this trial will be a necessary test of the amyloid hypothesis, which has had a major influence on Alzheimer’s research and drug development over the past 30 years.”

The new trial involves families with rare genetic mutations that cause Alzheimer’s at a young age – typically in a person’s 50s, 40s or even 30s. A parent with such a mutation has a 50% chance of passing the genetic mutation to a child, and any child who inherits the mutation is all but guaranteed to develop symptoms of dementia near the same age as his or her parent. This certainty gives researchers an opportunity to evaluate the effectiveness of drugs designed to prevent Alzheimer’s.

“It’s exciting to think of the valuable insights this groundbreaking trial will provide in the prevention of Alzheimer’s dementia,” said Fred Miller, GHR Foundation’s chief operating officer and Alzheimer’s program lead. “We’re pleased to partner boldly on the multiple DIAN-TU trials, all made possible by the strong collaboration between academic researchers, government, industry, philanthropy and the DIAN families themselves.”​

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From The New York Times:

"The study aimed to show that Alzheimer’s disease could be stopped if treatment began before symptoms emerged. The participants were the best candidates that scientists could find: still healthy, but with a rare genetic mutation that guaranteed they would develop dementia.

Now, the verdict is in: The drugs did nothing to slow or stop cognitive decline in these subjects, dashing the hopes of scientists.
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The results are a deep disappointment, scientists said — but not a knockout punch. The drugs did not work, but the problems may be fixable: perhaps the doses were too low, or they should have been given to patients much younger."

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GHR’s Health initiative partners with organizations using innovative trials to pursue the prevention of Alzheimer’s disease. One such trial is the Alzheimer’s Prevention Initiative (API) Generation Study which recently began enrollment in high-risk older adults to validate the use of genetic screening and identify an effective approach to prevent the disease.

Led by Dr. Eric Reiman and Dr. Pierre Tariot of Banner Alzheimer’s Institute (BAI), this pioneering multi-site prevention study is working to determine whether two investigational anti-amyloid compounds—an active immunotherapy and an oral medication—can prevent or delay the emergence of Alzheimer’s symptoms in people at a high genetic risk of developing the disease. The study will involve more than 1,300 cognitively healthy adults, age 60 to 75, who have inherited a copy of the e4 type of the apolipoprotein (APOE) gene from each parent. Roughly one in four people carry a single copy of the gene, which is strongly linked to late-onset Alzheimer’s.

The Generation Study is part of the API, an international collaborative led by BAI to accelerate the evaluation of promising treatments. The study is sponsored by Swiss pharmaceutical company Novartis and Thousand Oaks, Calif.-based biotechnology company Amgen in collaboration with BAI, with funding from the National Institute on Aging—part of the National Institutes of Health—as well as GHR, Alzheimer’s Association, Fidelity Biosciences Research Institute and Banner Alzheimer’s Foundation.

To learn more about how GHR is joining forces with industry, other philanthropic partners and the United States National Institutes of Health on the prevention of Alzheimer’s disease, contact us.

GHR Foundation attended the Alzheimer’s Association International Conference. As an important platform to present research and trend information, the forum saw global news coverage on potential new diagnostics, findings related to lifestyle and international rates of prevalence. 

A Wall Street Journal piece covering the conference entitled “Alzheimer's Disease Fight Focuses on Preventive Treatment” reinforces GHR’s focus on funding effective prevention therapies. It notes that “greater ability to measure the progression of the disease in the brain through the use of biological markers, such as the imaging of disease-related proteins, has made it easier to detect the subtle and slow progression of the disease...”

To advance our Alzheimer’s strategy, GHR’s Alzheimer’s advisory council convened a strategic meeting at the conference to discuss the impact of research, potential collaboration and next steps. The Foundation is pleased to be partnering with so many public and private sectors leaders in the fight against Alzheimer’s disease.

With a focus on Alzheimer’s disease prevention research, GHR Foundation funded a groundbreaking Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study which may help identify people who are highest risk to develop the disease. This research will also identify treatments – and when to best administer them – to slow or prevent Alzheimer’s. Long-term, the Foundation hopes the A4 study and complementary research will result in FDA approval for Alzheimer’s prevention therapies.

The A4 study team is continuing to develop the clinical partnerships necessary to study 1,000 patients and has created tools to share background with potential participants. GHR Alzheimer’s advisory board member and lead A4 researcher Dr. Reisa Sperling explains the research and how people can get involved in the research in a recent YouTube video. 

GHR looks forward to learning more about the impact of A4 on early detection and treatment of Alzheimer’s disease.