My Alzheimer's Journey
Part 68 - Interesting Prevention Clinical Trial
I learned this week about a clinical trial underway at Washington University in St. Louis. This international trial called the Primary Prevention Trial, is designed to determine whether stopping the early molecular changes that lead to Alzheimer’s disease can prevent the disease from ever starting. Specifically, the trial investigates whether remternetug — an investigational antibody being developed by Eli Lilly — can remove amyloid beta from the brain or block them from accumulating in the first place.
People as young as 18 are enrolled in the trial that was announced February 7, 2025. At this young age, the trial participants are generally about 25 years before the expected onset of dementia symptoms. The participants have few or no detectable Alzheimer’s-related molecular changes in their brains. However, the trial participants are members of families with genetic mutations that put them at high risk of developing Alzheimer’s disease.
The Washington University researchers believe if remternetug is successful with this targeted high-risk trial group, it would provide prevention and treatment for all forms of Alzheimer’s disease.
This trial is part of the Knight Family Dominated Inherited Alzheimer Network Trials Unit (DIAN-TU). The primary focus of this group of trials is to find medicines to prevent Alzheimer’s disease. Some of the funding for these trials comes from the National Institutes of Health (NIH). While led by Washington University School of Medicine, research institutes in North America, Australia, Europe, Asia and South America are involved in the trials. DIAN follows families with mutations in any of three genes that cause Alzheimer’s at a young age. According to the Washington University School of Medicine, “a child born into such a family has a 50% chance of inheriting such a mutation, and those who do so typically develop signs of dementia near the same age his or her parent did.”
Interestingly, the Primary Prevention Trial was originally designed for a different investigational drug — gantenerumab, by Roche/Genentech. This was in 2021. Roche/Genentech discontinued the development of gantenerumab in 2023 because Phase 3 trials failed to meet their clinical goals.
Remternetug was chosen as a replacement because early Eli Lilly trials showed promise in removing amyloid plaques. These early phase trials had similar results as Lilly’s infusion drug, donanemab. Two huge potential advantages of remternetug are:
can be given via injection just under the skin
dosing schedule of every three months
Results of the Primary Prevention Trial will determine the final dosing schedule. However, remternetug has the potential to be a more patient friendly drug than donanemab or lecanemab.
Each trial participant will be treated with remternetug, or a placebo, for two years.
I am well aware of the controversy surrounding the dominant amyloid cascade hypothesis. I personally believe that targeting amyloid beta is part of the overall treatment of Alzheimer’s - but, not the entire therapeutic solution.
Sources in addition to those linked in the article include:
Wouldn’t that be grand? I should be in that trial!