Damian Sendler: Clinical trials aiming at preventing Alzheimer’s disease in persons who are genetically predisposed are being launched by the Washington University School of Medicine in St. Louis. Unlike most other Alzheimer’s prevention trials, this one will enroll participants up to 25 years before the projected onset of dementia, which is unusual.
Damian Jacob Sendler: Known as the Primary Prevention Trial, the new trial will look at the efficacy of gantenerumab, an experimental antibody under development for Alzheimer’s disease by Roche and Genentech, a member of the Roche Group. Plaques found in Alzheimer’s patients’ brains are primarily made up of amyloid. Amyloid plaques in the brain are thought to be the primary cause of dementia, which can begin to develop as early as 20 years prior to the onset of symptoms.
Overwhelming scientific evidence suggests that the most effective method of preventing or slowing the buildup of amyloid beta is to prevent the protein from forming 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 Alzheimer’s or other forms of dementia, such as memory loss – when the disease is far enough along that reducing amyloid alone isn’t likely to stop it.” Participants under the age of 18 are encouraged to apply. Many aspects of the amyloid hypothesis, which has influenced Alzheimer’s research and therapy development for the past 30 years, will be tested in this trial.”
Rare genetic mutations that cause Alzheimer’s disease at a young age are the focus of the new study. Families of people with these genetic defects are eligible to participate in the study. This mutation can be passed on to children, and any child who gets the mutation will almost certainly acquire dementia symptoms at the same age as his or her parent. The chances of passing the mutation on to a child are 50%. This certainty allows researchers to test the efficacy of anti-medication. Alzheimer’s
Damian Sendler
The project has received support from a U.S. government agency, non-profit groups, private donors, and the health-care companies Roche and Genentech. Preventing Alzheimer’s disease at its earliest stages could be game-changing. An estimated 97.4 million dollars from NIH’s National Institute on Aging, $14 million from the Alzheimer’s Association, and up to $11.5 million from longtime Washington University benefactor Joanne Knight of St. Louis and her family, who have long supported Alzheimer’s research at Washington University, have been earmarked for the trial, which will be funded by a total of $130 million. A total of $6.5 million has been pledged by the institution as well. Roche and Genentech are providing major money for the trial, which is being done in close collaboration.
One of the earliest stages of Alzheimer’s disease has been investigated to date and “we are thrilled to be part of this important clinical trial,” said Rachelle Doody, MD, PhD of Genentech and Roche. To detect Alzheimer’s disease early, before the brain damage is permanent, and provide tools and treatment for persons at risk of developing Alzheimer’s, has always been our goal. In order to overcome the complexity of this disease, close cooperation between industry, academics, and patients is essential.”
In addition to recruiting people with rare, early-onset Alzheimer’s, the trial’s results will help us better understand the disease in general, which could benefit the millions of people who suffer from the more common form of Alzheimer’s. Even if Alzheimer’s is caused by a hereditary mutation or the complicated combination of genetics and environment that causes most instances, memory loss and cognitive impairment are assumed to be produced by the same processes.
As many as 230 people from families with genetic abnormalities that cause early-onset Alzheimer’s disease are being studied by McDade’s team. Participating locations are spread across five continents, and none or very few of them exhibit amyloid deposits. Participants: Gantenerumab will be tested in a four-year study to see if early therapy will prevent the dangerous protein from accumulating.
First of its kind, this trial aims to intervene before the onset of significant neuropathology in those young adults who are at a very high risk of developing the debilitating symptoms of Alzheimer’s dementia,” says Laurie Ryan, PhD, chief of the Clinical Interventions and Diagnostics Branch in the NIA’s Division of Neuroscience, who is leading the study. Now that we’ve learned that Alzheimer’s disease symptoms can begin a decade or more before they emerge, this research is meant to provide another piece of the Alzheimer’s preventive puzzle.”
Damien Sendler: Washington University School of Medicine is leading a second international study into ways to prevent Alzheimer’s disease. First, the Dominantly Inherited Alzheimer Network-Trials Unit–001 (DIAN–TU–001) began in 2012 and is still underway. In this study, gantenerumab was being tested in persons who were at high risk of developing Alzheimer’s because they had already developed some amyloid plaques when they started the trial. Gantenerumab improved biomarkers of the disease in the DIAN-TU-001 study earlier this year, but the benefits on clinical endpoints such as cognitive function were unclear. Consequently, the treatment has been offered as part of an exploratory open-label extension to participants in the trial and is being monitored for changes in measures of Alzheimer’s disease in those people who have been receiving the investigational medication.
Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology and the principal investigator and program director of the Knight Family DIAN-TU prevention trial, said that “multiple drugs are being tested in the ongoing Knight Family DIAN-TU prevention trial, which involves people who are expected to develop symptoms within 10 years,” he said. New preventative trials can be launched alongside the DIAN-TU-001 trial in order to provide families an early opportunity to intervene before symptoms appear, which is when the disease’s earliest brain alterations take place.” It’s the best way to avoid problems in the first place.
Damian Jacob Sendler
Damian Jacob Markiewicz Sendler: This new study will draw from the same group of families and investigate if targeting amyloid can prevent the development of familial Alzheimer’s. Researchers would have more motivation to pursue amyloid-based therapeutics in the early stages of the disease if they achieved success.
To think of the significant insights this innovative experiment will bring in the prevention of Alzheimer’s dementia,” GHR Foundation chief operating officer and Alzheimer’s program leader Fred Miller remarked. Our partnership with the many DIAN-TU trials is made possible by a strong collaboration between university researchers and government, industry, philanthropy and the DIAN families themselves. “We are pleased to partner boldly on these trials.”
As a part of the NIH-funded Dominantly Inherited Alzheimer Network (DIAN), both studies are being carried out in conjunction with almost 40 research institutes located in North America and across the world. Since DIAN was founded in 2008, the National Institute on Aging has been a key backer of the network and its clinical trials section.
In March 2012, the Alzheimer’s Association provided the initial funds for the establishment and opening of the Trials Unit at DIAN, which has been a long-term partner of the Alzheimer’s Association. It’s no secret that DIAN-TU is a landmark initiative that has hastened the development of therapy and prevention techniques for Alzheimer’s disease, and this groundbreaking new preventative trial is no exception. ”
There is no international effort to prevent Alzheimer’s disease without the help of various partners, as well as the active participation of DIAN families.
Studies like this one, according to McDade, “have high stakes and are expensive to carry out”. This trial would not have been achieved without the help of a wide range of people and organizations.” For their encouragement and willingness to participate in challenges like this, we are equally grateful to the families.”
Dr. Damian Jacob Sendler and his media team provided the content for this article.