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First large-scale trial of Alzheimer's prevention drug announced

First large-scale trial of Alzheimer's prevention drug announced

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The experiment will be conducted on members of the world's largest family afflicted with a genetic marker for the disease.

The U.S. announced on Tuesday an unprecedented drug trial aimed at preventing Alzheimer's, a disease that gradually causes dementia.

The experiment is unusual for two reasons: The drug will be administered to subjects who are ostensibly healthy. A majority of them will, however, be genetically predisposed to develop the disease.

Also, it will be one of the few experiments to be conducted on people with a genetic predisposition to any disease.

The subjects will mostly be members of the world's largest family afflicted with Alzheimer's. In this Colombian family, who reside in and around Medellin, those who have a specific gene mutation normally show first Alzheimer's symptoms at 45 and full dementia at 51. Eventually, not only do their memories fade, but also their ability to move, eat and communicate.

While the whole clan number 5,000, the $100 million, five-year trial, which begins in 2013, will be conducted on 300 subjects, some as young as 30. A few Americans unrelated to the family will be tested as well.

The drug

The drug, Crenezumab, targets one of the brain substances thought by many to be a cause of Alzheimer's: amyloid plaques. More specifically, ABC reports that it attacks ABeta, a component of those plaques, that accumulates in the brains of people with this genetic mutation.

The trial will look to see whether the drug helps delay or even prevent memory problems in the subjects with the genetic marker, and find out at what age the drug needs to be administered to prevent dementia.

If keeping the brain clear of clumps of amyloid plaques does appear to stave off memory decline, future trials could just look at amyloid levels to determine the success of a treatment rather than waiting to see whether patients' memories deterioriate.

Crenezumab was chosen because it does not yet appear to have negative side effects, whereas other amyloid-attacking drugs do. Researchers are currently conducting two clinical trials of the drug on people who have mild or moderate symptoms of dementia to see if it reduces their amyloid plaque levels or reduces their cognitive decline.

The experiment

The experiment will be composed of three groups of 100 people: 100 family members with the mutation who will receive the drug every two weeks; 100 with the mutation who receive a placebo; and 100 non-carriers who will also receive a placebo. (Because many people do not want to know whether they carry the gene, the presence of non-carriers means that participants won't know if they have it.)

Researchers will run a range of tests on the subjects. First, they will measure memory and cognition with a series of tests that detect otherwise unnoticed changes in recall and thinking. Some of the skills tested include recalling words, naming objects, nonverbal reasoning, remembering time and place, and drawing by copying complex figures.

They will also test the subjects' emotional states. Dr. Pierre N. Tariot, director of the Banner Institute and a leader of the study, told The New York Times, “irritability, sadness, crying, anxiety, impulsivity — these are cardinal features of the disease as it emerges.”

The researchers will also note physiological changes in the size of the brain, and in levels of amyloid and tau, a protein found in dying brain cells. Improvements in any of these areas would indicate to scientists that they could treat any of these early physiological changes in the same way that treating high blood pressure can help prevent heart disease.

Though the experiment is scheduled to last five years, tests could show whether the drug is effective as early as two years in.

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via: The New York Times, The Wall Street Journal, ABC News

photo: Garrondo/Wikimedia

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Laura Shin

Features Editor

Laura Shin has been published in The New York Times, The Wall Street Journal and The Los Angeles Times, and is currently a contributor at Forbes. Previously, she worked at Newsweek, the New York Times, Wall Street Journal and LearnVest. She holds degrees from Stanford University and Columbia University's Graduate School of Journalism. Follow her on Twitter. Disclosure