There have been several different advances in the Alzheimer’s disease (AD) field in recent years, from the approval of the first disease-modifying therapy since 2003 to improved biomarkers and prevention. As the population ages, the need for treatment in the early stages of disease becomes even more important. The amount of research on lifestyle decisions as modifiable risk factors for disease is burgeoning, and the benefits of choices such as exercise and diet are becoming better known among the general public.
Many of these lifestyle changes have been shown to reduce the risk of other diseases such as heart disease and diabetes that are linked to Alzheimer’s disease. Other risk factors have been identified, including high blood pressure, obesity, depression, smoking, hearing loss, and binge drinking. Banner, an executive at his Alzheimer’s Institute for his director, Eric Lyman, M.D., prevention is an important aspect of the disease and an area that could help shape the future of treatment.
At the 2022 Clinical Trials (CTAD) Conference November 29-December 2 in San Francisco, Calif., Reiman commented on different ways to improve prevention of AD. As part of a new iteration of NeuroVoices, he discussed prevention efforts including pharmacological strategies, positive lessons learned from failed trials, and reasons for excitement ahead. In addition, he touched on how preventive tactics could play a role in future research evaluating new treatments.
neurology live®: Other than lifestyle decisions, are there other precautions I can take?
Eric Lyman, M.D.: Let’s talk more generally about prevention research. As one of the leaders of the Alzheimer’s Disease Prevention Initiative, I have a long-standing interest in doing what I can to accelerate the evaluation and likelihood of approval of preventative therapies and to discover effective treatments by 2025. I had realistic possibility. This was a season of twists and turns, and a potentially game-changing event that included not only the exciting developments I mentioned, but also some disappointments.
We have completed the first NIH-supported prophylaxis trial of crenezumab, an anti-oligomeric antibody therapy, in non-cognitively impaired individuals at some risk of developing Alzheimer’s disease due to an autosomal dominant Alzheimer’s disease mutation. did. The drug had no significant effect on amyloid plaque burden and no significant clinical benefit. However, our power was limited in that effect. It’s heartbreaking to see such a negative discovery and to think that these heroic families are at such high risk. Also, a recent pivotal Phase 3 pivotal trial of gantenerumab in early AD made another heartbreaking finding. , we have continued to learn along the way. If it weren’t for some of these studies, there wouldn’t be ongoing preventive therapy.
we are all in this together. Despite these disappointments, there were some pretty serious disappointments last year, with a lot of disagreements and opinions about the interpretation of the prematurely discontinued treatment aducanumab. The results of the lecanemab and donanemab studies will support the idea that amyloid plays a role in the development of Alzheimer’s disease, offer a promising treatment for patients and families, and have a major impact on drug development. . I’m a psychiatrist and I don’t know anything about the mechanism of psychiatry, but there are drugs that work. There are drugs that work on the basis of serendipitous discoveries and established treatments, and knowing their biological effects could further inform early-stage drug development and accelerate approvals for future prevention, etc. The advent of these therapies will allow us to deploy these tools in ways that will further inform drug development. I am very excited about ongoing prevention trials such as AHEAD, which is being conducted with Eisai, and her TRAILBLAZER-3, which is being conducted by Lilly with colleagues and me in the Alzheimer’s Disease Prevention Initiative. We believe these provide the best way to find and support approval of preventative therapies faster than other methods.
In the meantime, unlike imaging techniques, with these promising blood-based biomarkers, we can go back to previous studies to reveal efficacy. Consider a lifestyle preventative therapy that may give you: Old blood samples can be used to do some very important things. Suggestions for cardiovascular health include lowering blood pressure, treating cholesterol levels, aerobic exercise, cognitive training, and a healthier diet more generally. If these things prove to be as helpful as they suggest, we can do some very important things.
First, we can examine whether the improvements we are seeing are related to a slowdown in Alzheimer’s disease itself. , healthy but already diseased people can be examined to see if these interventions have equivalent effects in healthy individuals with and without disease. We are excited not only for preventive therapies on drug development, but also for a variety of lifestyle interventions, including his FINGERS ongoing worldwide and as part of his POINTER study in the United States. Leverage these biomarkers to inform how these interventions work.
With diagnostic biomarkers associated with clinical benefit, we hope to be able to conduct prophylaxis trials in at-risk individuals, say, in 18 months, so that broader assessments can begin. . Develop promising preventive therapies and make them available to the public. If prophylactic therapy is to be used, it should be affordable and widely available. , that means they will be used to screen people over the age of 55 every two years. For all these reasons, we’ve seen some challenges and twists in this area, but it’s a very exciting time.
Edited transcript for clarity. Click here for more NeuroVoices.