Last year we wrote about the early ending of the Generation Program study due to the development of subtle memory problems among participants. In August of 2020, researchers from Novartis and Banner Alzheimer’s Institute shared their key findings with the scientific community at the virtual Alzheimer’s Association International Conference (AAIC).
The Generation Program trials aimed to prove that the drug umibecestat could delay the onset of Alzheimer’s dementia in healthy people with one or two copies of the APOE4 gene which increases a person’s risk for Alzheimer’s. One copy of APOE4 increases risk three- to fourfold and two copies increase the risk up to 15-fold.
The trial studied APOE4 carriers with no memory and thinking problems. Even though the study ended early, researchers were able to learn a lot about the drug being tested and the study’s design that will be helpful in designing future trials.
The study showed it was possible to recruit people at a higher risk of disease based on their genetic background. In fact, this is the world’s largest cohort of carriers of the APOE4 gene to be gathered for a scientific study. They provided a significant amount of information that will be helpful for future studies.
During the study the participants taking the drug performed worse on tests designed to measure cognition than those on the placebo. After the trial scientists followed the participants to find out if the memory worsening would improve once the medication stopped. Four months after their last dose, participants returned to the same level of memory and thinking as before the trial began. There were no lasting effects.
The study also monitored changes in brain volume. A reduction in brain volume was seen in people taking the study drug as compared to those on placebo. This reaction also reversed four months after the study ended.
Researchers can learn a great deal from the study. It is possible that the study drug and similar drugs called BACE inhibitors may still be effective at smaller doses or for people with specific characteristics. Both are worth more investigation. And the Generation Program collected a significant amount of information on the world’s largest group of APOE4 carriers. This body of knowledge will be useful to better understand the risk factors, learn more about the silent stages of the disease and plan for future prevention trials.
Alzheimer’s research is an ongoing process. Each study provides scientists with data that generate new hypotheses for how to prevent and treat this devastating disease. While the Generation Program was halted for good reasons, scientists are as committed as ever to ending Alzheimer’s disease before losing another generation.