The National Institutes of Health (NIH) has granted $5.5 million in funding to expand the first large-scale study that aims to identify drugs able to stop or slow the progression of Alzheimer’s disease, which is being conducted by the Washington University School of Medicine in St. Louis. The National Institute on Aging from the NIH will support the trial, dubbed the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU), with a total of $26 million over the next five years.
The DIAN-TU trial, which will be conducted in patients likely to develop the debilitating disease, will be particularly dedicated to study dominantly inherited forms of Alzheimer’s. Almost half of all late-onset patients suffering from Alzheimer’s have some link to a particular form of the gene Apoe4. Even though having it doesn’t mean suffering from the disease, the researchers believe that in dominantly inherited Alzheimer’s, a single copy of one of the critical mutations, which is determined by genetic screening, means a patient has a high probability of developing memory and other cognitive problems.
Therefore, the investigators created a detailed timeline of brain alterations even before the first symptoms of dominantly inherited Alzheimer’s, which may strike in a person’s 30s, 40s, or 50s. During the trial, they will analyze two treatments in patients to understand if they can stop or slow the progression of Alzheimer’s and its symptoms. A third drug may be added to the trial, as the researchers continue to work with pharmaceuticals to identify another one.
The funding will enable the participants to continue undergoing the medication they receive during the initial stage of the trial, the biomarker testing phase, until its final stage, the cognitive endpoint phase. Most clinical trials typically need to pause or stop in order to conduct a detailed evaluation of the work done — usually at phase 2 — and then start a new a larger phase 3 clinical trial to continue research. In this project, however, the investigators believe that with the help of the NIH, they will be able to conduct their DIAN-TU trial differently.
“This new grant lets us keep the train rolling as long as it still seems to be moving toward the goal,” said the principal investigator Randall Bateman, MD, of the School of Medicine. “As long as we have a treatment that appears to be safely doing what it’s designed to do, we can continue to treat and monitor DIAN-TU trial participants.”
Researchers have already engaged in the initial biomarker phase of the study, and are looking for early clues that indicate that the drugs have the desired effects. During the cognitive endpoint phase, investigators will be able to assess its long-term effects, as well as capacity to prevent or slow the disease. It is also in the last phase of study that they will have collected the needed critical data namely for the U.S. Food and Drug Administration to consider for potential investigational drugs.
“This approach, called seamless adaptive trial design, enables us to condense the stages of the trial so it finishes three years earlier than the decade it normally would take,” explained Bateman, who is a Charles F. and Joanne Knight Distinguished Professor in Neurology. “Thanks to the support of this grant, the current DIAN-TU trial may lead to approved preventive treatments for dominantly inherited Alzheimer’s disease.”
The seamless process is being used by the DIAN-TU researchers, since it was granted by regulators as a way of enhance and accelerate new drug testing, as well as in recognition of the urgent need for treatments for inherited Alzheimer’s. The National Institute on Aging has been supporting the work of Bateman and his research team since 2012. It has already been used in funding research projects regarding diseases like cancer and heart disease, but this is first time it is being used for Alzheimer’s.
“By providing us with this grant, the National Institute on Aging has made it possible for us to safely accelerate the journey toward a new era of preventive treatment for inherited Alzheimer’s disease,” Bateman said. “We can’t say now if any of these new drugs will be successful, but we’re looking forward to working at a faster pace with pharmaceutical companies and regulatory agencies to find effective treatments.”
In addition, the NIH funding will also be used to enroll between 300 and 400 new participants and include 10 to 15 additional study sites in the United States, Canada, Australia, and Europe. The DIAN-TU trial was also awarded a $4.2 million grant from the Alzheimer’s Association, as well as financially supported by pharmaceutical companies, which donated treatments, and by private companies, which offered a brain plaque imaging agent and a computerized cognitive skills test.