Exciting New Trial Seeks to Prevent Alzheimer’s Before Symptoms Appear

A groundbreaking clinical trial is underway with the aim of halting Alzheimer’s disease long before symptoms even develop. The Primary Prevention Trial specifically targets individuals from families with genetic mutations that virtually guarantee they will develop Alzheimer’s disease at a relatively young age, usually in their 30s, 40s, or 50s. The objective is to utilize these participants to uncover effective prevention methods that could benefit all forms of Alzheimer’s.

The Role of Amyloid Beta in Alzheimer’s Development

Research indicates that Alzheimer’s disease begins with the buildup of amyloid beta protein in the brain, a process that can start as early as two decades before cognitive and memory issues arise. The trial focuses on utilizing an investigational antibody named remtersetug—developed by Eli Lilly and Company—to either remove these amyloid beta plaques or impede their formation from the outset. The hope is to intervene during the early, symptom-free phase of the disease, effectively stopping its progression and preventing the onset of symptoms altogether.

“We have seen tremendous progress in the treatment of Alzheimer’s disease in recent years. Two amyloid-targeting drugs were shown to slow symptoms, and have now been approved by the FDA for mild cognitive impairment or mild dementia. This supports our hypothesis that intervening early, when amyloid beta is at its earliest stage, could prevent symptoms from emerging.”

Eric McDade, DO, Professor of Neurology, Principal Investigator of the Trial

Background and Design of the Primary Prevention Trial

This trial is part of the Dominantly Inherited Alzheimer Network (DIAN) Trials Unit (DIAN-TU), which seeks to discover medications capable of preventing or treating Alzheimer’s disease. DIAN-TU is aligned with the DIAN, a NIH-funded international research network involving various research institutions globally. DIAN surveillance includes families with mutations in any of three genes responsible for early-onset Alzheimer’s. Children from such families have a 50% likelihood of inheriting these mutations, typically leading to dementia at the same age as their parent.

The Primary Prevention Trial enrolls participants from these families, both those with and without the mutation. Noncarriers serve as a comparison group. Participants must be at least 11 years younger than their estimated symptom onset age based on family history, exhibit no cognitive impairment, and have minimal amyloid deposits in their brains.

Stakeholder Support and Fundamentals of the Study

More than $130 million has been allocated to fund this critical research. The trial benefits from substantial support by the National Institutes of Health’s National Institute on Aging (NIA), the Alzheimer’s Association, and the GHR Foundation. These entities have contributed an estimated $98.3 million, $14 million, and additional funds, respectively. Additional backing comes from Joanne Knight and family, committed donors whose $11.5 million contribution further enhances the study.

Eric McDade, the trial’s principal investigator, anticipates reporting results within four to five years, contingent on meeting participation goals. The study will track the disease development in participants over the course of two years, with those carrying the mutation receiving the option to continue drug administration for another four years post-study under an open-label extension.

Patient Testimony: Hannah Richardson

Hannah Richardson, a twenty-four-year-old participant, shares a personal connection to the disease. Her grandfather, grandmother, most of her uncles, and mother each succumbed to Alzheimer’s. Growing up, Richardson’s mother openly shared her journey, inspiring her to follow in her footsteps and contribute to research efforts. Her participation emphasizes the critical role of individuals like her in advancing Alzheimer’s knowledge.

Shift in Investigational Drug and Trial Design

The trial initially planned to use gantenerumab, a different investigational antibody, developed by Roche/Genentech. However, development ceased after data from other Alzheimer’s trials cast doubt on its efficacy. Remtersetug, the antibody now in use, exhibits strong capabilities in removing amyloid plaques. This makes it comparable to donanemab, an FDA-approved Alzheimer’s therapy by Eli Lilly. Additionally, remtersetug offers a more convenient administration method, via subcutaneous injections given every three months, in contrast to the IV infusion required for FDA-approved treatments.

“We are pleased to partner with the DIAN-TU team to evaluate whether remtersetug can help slow or prevent the accumulation of amyloid plaque, a defining event in the early cascade of Alzheimer’s disease onset.””

Mark Mintun, Group Vice President-Neuroscience R&D at Lilly

Impact and Future Potential

This innovative study represents a significant leap forward in the quest to effectively address Alzheimer’s disease. While the trial primarily targets families with early-onset Alzheimer’s, its findings could have far-reaching implications for the broader Alzheimer’s patient population. By understanding the preventive measures that work early in the disease process, researchers can develop treatments that might delay or even stop the progression of Alzheimer’s in individuals with more common forms of the disease.

The involvement of numerous stakeholders, including academic researchers, government agencies, industry leaders, and philanthropic organizations, underscores the critical importance of this research. Collectively, their efforts aim to offer hope to those affected by Alzheimer’s, paving the way for more effective prevention strategies in the future.

Next Steps and Future Directions

Over the next few years, researchers will closely monitor the study’s participants. The trial’s success could potentially pave the way for new preventive treatments, benefiting millions of people worldwide. As the field of Alzheimer’s research continues to progress, studies like the Primary Prevention Trial remain pivotal in our ongoing battle against the disease.

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