An international clinical trial is being launched aimed at preventing young-onset Alzheimer’s disease in people genetically destined to develop the illness.
Unlike most other Alzheimer’s prevention trials, this will enrol people before the disease has taken hold, up to 25 years before the expected onset of dementia.
The Primary Prevention Trial, led by Washington University School of Medicine in St. Louis, will investigate whether gantenerumab — an investigational antibody under development for Alzheimer’s disease by Roche and Genentech — can clear a key Alzheimer’s protein called amyloid beta, and slow or stop the disease.
Amyloid is the chief component of plaques that dot the brains of people with the disease.
Many scientists suspect the disease originates from the buildup of amyloid plaques in the brain that start to develop up to two decades before symptoms of dementia begin.
“Overwhelming evidence suggests that the most effective way to slow or stop amyloid beta is to prevent it from building up in the first place, but most of the drugs targeted to this protein have been tested in people who already have at least some early signs of the disease, such as memory loss – when the disease is far enough along that reducing amyloid alone isn’t likely to stop it,” said Dr Eric McDade, an associate professor of neurology and the trial’s principal investigator.
“We’ll be recruiting participants as young as 18. In many ways, this trial will be a necessary test of the amyloid hypothesis, which has had a major influence on Alzheimer’s research and drug development over the past 30 years.”
The new trial involves families with rare genetic mutations that cause Alzheimer’s at a young age – typically in a person’s 50s, 40s or even 30s.
A parent with such a mutation has a 50 per cent chance of passing the genetic mutation to a child, and any child who inherits the mutation is all but guaranteed to develop symptoms of dementia near the same age as his or her parent.
This certainty gives researchers an opportunity to evaluate the effectiveness of drugs designed to prevent Alzheimer’s.
More than $130million has been earmarked for the trial, including grants totalling an estimated $97.4million from the National Institute on Aging (NIA) of the National Institutes of Health (NIH), $14million from the Alzheimer’s Association and the GHR Foundation, and up to $11.5million from longtime Washington University benefactor Joanne Knight of St. Louis and family, who have long supported Alzheimer’s research at Washington University. In addition, the university has pledged to raise an additional $6.5 million.
The trial is being conducted in close partnership with Roche and Genentech, which also is providing significant funding.
“We are thrilled to be part of this important clinical trial in one of the earliest stages of Alzheimer’s studied to date,” said Dr Rachelle Doody, global head of neurodegeneration at Roche and Genentech.
“Our vision has always been to detect Alzheimer’s early, before damage in the brain is irreversible, offering tools and treatment all along the journey for people at risk of the disease.
“Close collaboration between industry, academia and patients is so critical to achieve this and tackle the complex challenge of this disease.”
The trial will recruit people with rare, early-onset forms of the disease, but the results also will further understanding of Alzheimer’s overall, which could benefit the millions of people living with the more common form, which affects people later in life.
Dr McDade and his team are studying about 230 participants from families that carry genetic mutations that lead to early-onset Alzheimer’s disease.
The participants come from sites on five continents and have no or very few amyloid deposits.
The trial will test gantenerumab over four years, with a goal of determining whether early treatment will prevent the buildup of the toxic protein.
