The Alzheimer’s Prevention Initiative’s (API) Generation Program recently announced it was stopping a drug study aimed at preventing Alzheimer’s disease. The drug, called a BACE inhibitor, was a promising prevention therapy. Researchers hoped it would block the growth of beta-amyloid in the brain to stave off the development of Alzheimer’s symptoms. However, safety studies revealed that the drug caused early worsening in some measures of memory and thinking.
“We learned over the last year that other studies were finding an unexpected negative effect on memory and thinking with this type of medication,” explains Pierre Tariot, MD, Director of the Banner Alzheimer’s Institute in Phoenix and a principal investigator in the study. “This prompted us to add additional safety reviews in order to check for this type of finding more carefully, to protect our participants. Unfortunately, we found the same disappointing result causing us to stop the trial.”
Even though it ended early, researchers can learn a great deal from the study. For example, the Generation Program proved that it was possible to recruit people at high risk for the disease based on their genetic background. The study collected a significant amount of information on the world’s largest cohort of APOE4 carriers. (APOE4 is a gene known to significantly increase a person’s risk of developing the disease.) This body of knowledge will be useful to better understand this genetic risk factor, learn more about the silent stages of the disease and plan for future prevention trials.
The Generation Program team, which consists of scientists from Novartis and Amgen pharmaceutical companies and Banner Alzheimer’s Institute, plans to follow and evaluate the participants with the same assessments used in the trial. This will allow them to better understand the effects of stopping this type of therapy and gather data that could be helpful for future trials.
“Our research participants are pioneers in the study of Alzheimer’s disease,” says Dr. Tariot. “Their participation has had a positive impact on how to conduct trials in people with a genetic risk for the disease. We are extremely grateful to them. And we are working on a plan to stay connected with them until our next prevention trial is available.”
What’s next for Alzheimer’s research?
Scientists know that BACE inhibitors can reduce the buildup of beta-amyloid in the brain, one of the key brain changes in Alzheimer’s. What they don’t yet understand is why this class of drug has a negative impact on memory and thinking, if that effect is reversible after stopping the drug or if a lower dose will provide different results.
While Alzheimer’s researchers continue to study the possibilities of BACE inhibitors, there are other promising strategies in various phases of research including:
“These study results remind us that the scientific process is quite daunting,” says Dr. Tariot. “We are dealing with a devastating human illness that is very complicated. Finding new and effective treatments or prevention therapy is a marathon, not a sprint. One thing I can assure you is that we will not give up.”