Trial aims to prevent Alzheimer’s in those genetically predisposed

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A first-of-its-kind study is testing the use of antibody drugs to prevent or slow down the onset of Alzheimer’s disease in individuals genetically destined to develop the illness at an early age.

“We want to stop this disease in its tracks, before symptoms begin to emerge, or when in the very early stages,” says Dr. Mario Masellis, neurologist and lead investigator of the trial at Sunnybrook Health Sciences Centre, one of the few Canadian sites of an international study – The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) drug trial.

Autosomal dominant Alzheimer’s disease (ADAD, or also referred to as early-onset familial Alzheimer’s disease) is genetically inherited or passed down through families. Individuals who have a parent with a genetic mutation have a 50 per cent chance of carrying the gene.

Those who have the gene will begin to experience symptom onset as early as their 30s and 40s; generally 20 to 30+ years earlier than the majority of people whose Alzheimer’s develops sporadically later in life.

Scientists suspect that the build up of a sticky plaque in the brain made up of a protein called beta-amyloid and another, called tau protein, may be the first steps in a process in the development of Alzheimer’s disease (AD). Amyloid and tau changes in the brain have been shown to occur greater than 15 years before symptoms appear in genetic cases.

“We think amyloid is the initiating effect,” says Dr. Masellis, also an assistant professor of neurology at University of Toronto. “When it starts to gum up and stick together, we think it causes inflammation of brain cells leading to memory and thinking impairment, and eventually pre-mature brain cell death.”

In what is one of the longest and most aggressive preventive Alzheimer’s drug trials in history, the researchers are testing two experimental anti-amyloid drugs, solanezumab and gantenerumab, both of which aim to lower levels of the substance that forms amyloid plaques.

While ADAD makes up less than one per cent of all Alzheimer’s cases, the predictable age of onset makes it possible to test drugs years before symptoms begin. This is when anti-amyloid therapies are hypothesized to be most effective.

“The Alzheimer’s Association feels confident that this study will help to accelerate the scientific community’s ability to determine whether an early intervention can delay or stop Alzheimer’s disease,” says Dr. Maria Carrillo, Ph.D., chief science officer at the Alzheimer’s Association.

Dr. Randall J. Bateman of Washington University School of Medicine, the study’s principal investigator, says, “The important milestone of reaching the first stage of enrollment brings us one step closer to finding out whether these two drugs will work as preventive therapies. We will keep going until there are drugs to effectively prevent and treat Alzheimer’s disease.”

A novel approach for the field of Alzheimer’s disease research, this study has an adaptive clinical trial design, which means there is potential for adding new drugs to the trial for testing, as they become available.

DIAN-TU is a public-private partnership of academic centers, the Alzheimer’s Association, Eli Lilly and Company, Roche, and the U.S. National Institute on Aging, amongst other supporters.

The ADAD population has historically been excluded from Alzheimer’s trials due to the rarity of this disorder and hypothesized different routes to disease compared to sporadic, late-onset Alzheimer’s disease. The DIAN-TU trial is the first global trial to enrol dominantly inherited Alzheimer’s participants and is currently operational at 24 sites in seven countries and four languages.

More information on the study is available at: www.dianexr.org or 1-844-DIAN-EXR (844-342-6397).