In a pioneering effort to prevent Alzheimer's disease before symptoms emerge, Washington University School of Medicine in St. Louis has begun enrolling participants in an international clinical trial targeting young adults at high genetic risk for the disease. The groundbreaking study marks a significant shift in Alzheimer's research, moving from treatment to prevention in individuals decades before expected symptom onset.
The Primary Prevention Trial will evaluate remternetug, an investigational antibody developed by Eli Lilly and Company, designed to either remove amyloid beta plaques from the brain or prevent their initial accumulation. This approach targets the disease process at its earliest stage, potentially preventing cognitive decline before it begins.
Novel Approach to Early Intervention
The trial focuses on individuals from families carrying genetic mutations that virtually guarantee early-onset Alzheimer's development, typically in their 30s, 40s, or 50s. Participants must be 11 to 25 years younger than their expected age of symptom onset and show minimal to no amyloid deposits in their brains.
"We have seen tremendous progress in the treatment of Alzheimer's disease in the past few years," explains Dr. Eric McDade, principal investigator and professor of neurology at WashU Medicine. "Two amyloid-targeting drugs were shown to slow symptoms of the disease and have now been approved by the FDA. This provides strong support for our hypothesis that intervening when amyloid beta plaques are at the very earliest stage could prevent symptoms from emerging in the first place."
Trial Design and Implementation
The study will enroll approximately 240 participants, including both carriers and non-carriers of the genetic mutations, with the latter serving as a comparison group. Remternetug will be administered via subcutaneous injection every three months, offering a less invasive alternative to current FDA-approved treatments that require intravenous infusion.
Hannah Richardson, a 24-year-old trial participant, represents the personal impact of this research: "My grandfather passed away from Alzheimer's, and so did his mother and all but one of his brothers. My mom and my uncle have been participating in DIAN trials since I was about 10 years old... I am happy to be involved in the Primary Prevention Trial because I know how important it is."
Collaborative Funding and Support
The trial has secured over $130 million in funding through a collaborative effort involving:
- $98.3 million from the NIH's National Institute on Aging
- $14 million from the Alzheimer's Association and GHR Foundation
- Additional support from WashU Medicine, the Knight family, and Eli Lilly and Company
"This innovative study in this special Alzheimer's patient population has the potential to significantly impact how we prevent Alzheimer's disease," says Maria C. Carrillo, PhD, Alzheimer's Association chief science officer.
Future Implications
While the initial two-year treatment period will focus primarily on preventing amyloid plaque accumulation, participants carrying the genetic mutation will be eligible for an additional four years of treatment in an open-label extension. The research team expects to report results within four to five years, depending on enrollment progress.
Fred Miller, GHR Foundation's Chief Operating Officer, emphasizes the broader implications: "For the first time, we're working to prevent the buildup of Alzheimer's pathology before it starts. The research will provide insight on how we prevent Alzheimer's disease for these families, as well as the nearly 13 million Americans projected to have Alzheimer's disease by 2050."
