Landmark Alzheimer's Prevention Trial

May 17th, 2012

Genentech, the Banner Alzheimer's Institute and the National Institutes of Health partner for first-ever study of cognitively healthy individuals

Genentech, the Banner Alzheimer's Institute, and the National Institutes of Health have collaborated on the first-ever prevention trial in cognitively healthy individuals who are likely to develop Alzheimer's disease due to their genetic history.

The landmark trial was the first to assess the potential of a medicine to stop Alzheimer's before it starts and is the cornerstone of a new international collaborative, the Alzheimer's Prevention Initiative (API), formed to accelerate the evaluation of promising but unproven prevention therapies. The study took place in Medellin, Colombia and involved about 250 participants from local families that can be traced to a common descendant. The participants share a rare genetic mutation that typically triggers Alzheimer's symptoms around age 45.

The study involved crenezumab, a humanized monoclonal antibody, which is designed to bind to beta-amyloid , the main constituent of amyloid plaque in the brains of patients with Alzheimer's disease. Beta-amyloidis proposed to be causative in the development of the disease.

Why this trial is historic

• The trial studied patients before they showed any symptoms of cognitive decline.
• There is significant unmet medical need within this unique patient population.

Significance and description of the trial

• A shift in the research paradigm

  This trial represents a significant shift in Alzheimer's disease research: from trying to reverse the damage to early prevention - which could be a decade or more before symptoms surface. If successful, this approach may allow earlier evaluation of promising medicines.

  Because of the potential impact, Genentech agreed to share data and findings with the entire research community after the trial is completed. This transparency could help further advance Alzheimer's research and encourage investigation of additional disease biomarkers. Furthermore, the findings may lead to similar studies in people at risk for the disease later in life.

• Unmet medical need in a unique patient population

  The patient population in Colombia offers a truly unique opportunity because of its size, its shared genetic background and its long legacy with Alzheimer's. Indeed, no other location in the world offers a sufficiently large number of mutation carriers close to their age of potential disease onset for a study to determine whether a prevention treatment may work. This large, extended family has as many as 5,000 living members, many of whose own families have been devastated by the disease. The New York Times has covered the story of this family extensively.

  See Related resources for links to the Times coverage.

• About the amyloid hypothesis

  The amyloid hypothesis proposes that the accumulation of toxic beta-amyloid(a sticky protein also called beta amyloid peptide) leads to Alzheimer's. The beta-amyloid protein is found in the plaques that accumulate in the brain and are the hallmark of Alzheimer's. By the time significant cognitive impairment starts to occur, patients already have a lot of amyloid plaque and their neurological function has begun to deteriorate.

  "The question is," says Sean Bohen, senior vice president, Genentech Early Development, "if we intervene before cognitive function deteriorates, can we prevent the disease?"

• Who's participating in the study

  Two groups of patients, totaling as many as 324 people, will be involved in the study. About 300 live in the Antioquia region of Colombia, which includes the city of Medellín and is home to nearly 5,000 people who share the risk for a rare genetic mutation. This mutation, presenilin 1 (PSEN1), causes early-onset Alzheimer's in any individual who is a carrier. It was first identified in 1995.

  Just over 100 participants will be mutation carriers who will receive the investigational treatment. Just over 100 participants will be mutation carriers who receive a placebo. Because most of those involved do not want to know their genetic status, just over 100 participants will be non-carriers who, since they have no risk for developing the disease at an early age, will only receive the placebo.

  Participants will be 30 or older and within 15 years of the age when their parent's symptoms began (the age of clinical onset). Typically, mild cognitive impairment due to Alzheimer's begins in the Colombian families around 45.

  In the United States, participants will be up to two-dozen individuals also at high risk for the disease because their family history indicates other, similar genetic mutations that are implicated in early-onset Alzheimer's.

Related resources

People who are interested in supporting Alzheimer's prevention initiatives in the United States are encouraged to join the API's Alzheimer's Prevention Registry. The registry is a community of people interested in the possibility of participating in Alzheimer's prevention studies, now or in the future.

Richard Scheller discusses the trial

Watch the interview series with Genentech's Executive Vice President of Research and Early Development,Richard Scheller.