"Treating Alzheimer’s patients as early as possible — when symptoms and brain pathology are mildest — provides a better chance of slowing cognitive decline, a large study of an experimental Alzheimer’s drug presented Monday suggests. The study of 1,736 patients reported that the drug, donanemab, made by Eli Lilly, can modestly slow the progression of memory and thinking problems in early stages of Alzheimer’s, and that the slowing was greatest for early-stage patients when they had less of a protein that creates tangles in the brain."
"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."
Neurologist Eric McDade, DO, meets with Marty Reiswig, a participant in Alzheimer’s prevention trials at Washington University School of Medicine in St. Louis. Reiswig comes from a family with a genetic mutation that puts carriers at high risk of developing Alzheimer’s. McDade is the director of a new Alzheimer’s prevention trial involving young adults from high-risk families. The trial is evaluating whether an investigational drug can clear a key Alzheimer’s protein called amyloid beta, and slow or stop the disease.
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.”
Wash U: Investigational drugs didn’t slow memory loss, cognitive decline in rare, inherited Alzheimer’s, initial analysis indicates
Randall J. Bateman, MD, of Washington University School of Medicine in St. Louis, led an international trial evaluating whether investigational drugs could slow memory loss and cognitive decline in a rare, inherited form of Alzheimer's disease. The trial was conducted at 24 sites in Australia, Canada, France, Spain, the United Kingdom and the United States.
From Washington University School of Medicine in St. Louis:
"An international clinical trial evaluating whether two investigational drugs can slow memory loss and cognitive decline in people in the early stages of a rare, inherited form of Alzheimer’s disease has yielded disappointing results, an initial analysis of the data has shown. However, the researchers continue to explore data from the trial’s cognitive and clinical outcomes, and await analyses of biomarkers and other information so they can further understand the study’s results."
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.
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."
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’s Health initiative partners with organizations pursuing the prevention of Alzheimer’s disease, targeting funding to improve some of the largest research efforts in the field. One such partner is Washington University’s Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). The DIAN-TU was formed to design and implement prevention trials for dominantly inherited Alzheimer’s disease, caused by a genetic mutation.
This rare form of Alzheimer’s disease results in early-onset of the disease with symptoms starting as early as a person’s 30s and 40s. The DIAN-TU launched a prevention study in this rare population testing experimental drug therapies that may stop the progression of Alzheimer’s disease before symptoms emerge. The trial is currently fully enrolled for the first two drugs and operational in 24 sites across six countries, with interim results expected in 2017 and final results by 2019.
The DIAN-TU builds on Washington University's Dominantly Inherited Alzheimer Network Observational study which collects observational data on persons with these genetic mutations. The DIAN study is operational in 17 sites across six countries, many of which are also DIAN-TU trial sites.
Washington University is currently planning its DIAN-TU Next Generation trials, which will test two additional potential treatments and novel diagnostic approaches with the dominantly inherited Alzheimer’s disease population. The DIAN-TU project gained attention recently in Germany during the first meeting of German families with the mutations. Attendees were informed about Alzheimer’s clinical trials and the DIAN-TU trials in particular, and had the opportunity to pose questions to researchers. All eligible attendees indicated interest in enrolling in future studies. Given the requirement for multiple sites to meet recruitment goals in this rare population, the participation of the German families is an important step for the DIAN-TU Next Generation Trials.
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. To learn more about the DIAN-TU Study, visit www.dianexr.org or call 1-844-DIAN-EXR (844-342-6397).
GHR Foundation’s Health Initiative is targeting funding to improve some of the largest Alzheimer’s prevention research efforts in the field, including Washington University Medical School’s DIAN-TU Study. This study is quickly evaluating potential prevention treatments among people with a rare genetic trait that causes the onset of the devastating disease in the prime of their lives.
The DIAN-TU Study was recently profiled by PBS’ SciTech Now program, which interviewed Dr. Randall Bateman, Dr. John Morris and a participant of the study. The DIAN-TU segment is the first of three in the 26-minute show, and continues in an interview at the end. This touching and informative profile illustrates not only the science behind the study, but the implications of the disease and what motivates participants.
To learn more about how GHR is joining forces with industry, other philanthropic partners and the United States National Institutes of Health for the prevention of Alzheimer’s disease, contact us.
GHR’s Health Initiative has committed more than $17 million over 5 years to scaling up important Alzheimer’s disease prevention research already underway. The Foundation is targeting funding to improve some of the largest research efforts in the field, including Washington University's DIAN-TU Study, which is quickly evaluating potential prevention treatments among those who are most likely to develop the disease, and Harvard University's A4 Study, which is working toward FDA approval for prevention therapy in the general population.
A recent Nature article highlights the importance of preclinical treatments, like DIAN-TU, which are initiated in cognitively unimpaired at-risk people, and are intended to postpone, reduce the risk of or completely prevent the clinical onset of Alzheimer’s. The authors argue that we need faster ways to evaluate these treatments, new ways to collaborate towards common goals and determination to expedite preclinical trials.
One useful tool for accelerating the initiation and performance of these trials is Collaboration for Alzheimer’s Prevention (CAP), a convening and consensus-building initiative co-founded by DIAN-TU and A4, among others. Important strides made by CAP include:
These developments help carry out Alzheimer’s prevention trials with care, thoroughness and maximum impact. While all research is uncertain, the potential to turn the tide and provide hope for all families that face Alzheimer’s has never been more promising. To learn more about GHR’s Alzheimer’s prevention funding efforts, contact us.
GHR Foundation’s Health Initiative is dedicated to a game-changing undertaking—the prevention of Alzheimer’s disease. The Foundation is targeting funding to improve some of the most important research efforts in the field, including Washington University's DIAN-TU Study. This trial focuses on rapid testing of prevention therapies among families that are most likely to develop the disease.
Recently, DIAN-TU announced it has completed participant enrollment for the first stage of the trial. This enrollment milestone means the first biomarker results will be available at the end of 2016, with the final cognitive endpoint expected in late 2019. This first stage will determine the effects of two drugs targeting amyloid plaques, which are believed by some scientists to be the first step in the process leading to cognitive impairment.
We will keep going until there are drugs to effectively prevent and treat Alzheimer’s disease.” –Dr. Randall Bateman, Washington University
The DIAN-TU team is working with the next generation of innovative drugs and study designs, and expects enrollment for new drugs. To learn more about DIAN-TU and GHR Foundation’s involvement in other innovative Alzheimer’s prevention trials, contact us.