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Cleveland Clinic Launches First In Human Trial to Test Cancer Drug's Effects on Reversing Alzheimer's Disease

Lou Ruvo Center for Brain Health Studying Bexarotene on the Heels of Recent Study Showing Significant Reduction in Amyloid Levels in Mice

September 9, 2013

Researchers at the Cleveland Clinic Lou Ruvo Center for Brain Health have begun a landmark Phase IIa clinical trial to determine if bexarotene (Targretin™), a drug currently FDA approved to treat skin cancer, can remove a protein build-up in the brains of Alzheimer’s patients, as it did in a recent animal study.

Known as the BExarotene Anti-amyloid Therapy for Alzheimer’s Disease (BEAT-AD) study, this is the first human trial in the world of bexarotene to treat Alzheimer’s disease. It is an investigator-initiated, proof-of-concept study led by Dr. Jeffrey Cummings, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health, and Dr. Kate Zhong, Senior Director of Clinical Research Development at the Cleveland Clinic Lou Ruvo Center for Brain Health.

Alzheimer’s disease is a complex brain disease in which the first recognizable abnormality is the accumulation of a protein in the brain called “amyloid,” which is normally cleared from the brain in healthy individuals. Many of the treatment approaches currently being studied in clinical trials are aimed at reducing the production or increasing the removal of this protein. Oral medications and vaccines are also being developed to try to control this protein, but no drug has yet proven to be effective against the amyloid protein.

According to a recent study published in the journal Science, mice genetically engineered to produce the amyloid protein showed a substantial reduction in amyloid levels in the brain within days of using bexarotene. The dramatic reduction was accompanied by improved performance on several measures of cognition and behavior.

“We were encouraged by this remarkable effect and realized that, because it was FDA approved, we could test it with Alzheimer’s patients immediately,” said Dr. Cummings, who is a paid consultant for Eisai Pharmaceuticals, the manufacturer of bexarotene. “If it works the same way in humans as it did in Mice, it will be a wake-up call to all of us in the Alzheimer’s research community that this drug and its unique mechanism for removing amyloid needs to be explored more closely.”

Because bexarotene is approved for skin lymphoma in humans, the dosing, side effects and methods of manufacture are already known. Additionally, this type of cancer occurs most commonly in the elderly population, so the drug has already been tested and found to be safe in an older patient group. The drug has known side effects as many cancer drugs do, all of which are being carefully monitored in the study.

BEAT-AD is a double-blind, placebo-controlled study being conducted at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. A total of 20 patients with mild to moderate Alzheimer’s disease will participate in the eight-week study. Patients will be randomized into either an active treatment or placebo group and will take the treatment drug orally two times per day. The protocol was designed to allow for everyone who participates in the trial to eventually be treated with the drug. Some will have two months of treatment while some will have one month, depending on which group they are randomized to at the outset.

The trial comes at an important time in Alzheimer’s research, now that a new diagnostic agent called florbetapir (Amyvid™) is FDA approved for use during Positron Emission Tomography (PET) imaging of the brain to measure the level of amyloid plaques.

“With this biomarker, we are able to determine the effect of bexarotene on our primary outcome, amyloid in the brain of Alzheimer’s patients, in an objective, precise way,” said Dr. Zhong.

Participants will have multiple clinical and neuropsychological evaluations, blood tests, and brain scans throughout the two-month study, including a florbetapir PET scan at the screening visit, at the four-week mark and at the conclusion of the study (eight weeks). Participants will have their amyloid blood levels measured during the study to see signs of the protein exiting the brain. A team in the behavioral neuroscience lab led by Dr. Jefferson Kinney at University of Nevada at Las Vegas (UNLV) will conduct these tests. UNLV will also be providing genotype analysis for all participants as a way to integrate genetic medicine into drug discoveries. The research team will be looking at whether patients with various kinds of apolipoprotein E (APOE) gene have different responses to bexarotene.

In addition to conducting the study, Cleveland Clinic Lou Ruvo Center for Brain Health designed the protocol and lined up all of the collaborators necessary to perform the array of services and expertise essential to this landmark study. Several philanthropists also stepped up to help fund the trial. The Center has grown to be one of the leading centers for conducting clinical trials in neurodegenerative disorders in the world.

“We put all of our best science and planning into this experiment because it is very, very important research that needs to be done,” said Dr. Cummings. “This study is funded exclusively by philanthropy, which is inspiring to me and shows the true impact that donors can have on advancing research. In addition to their generosity, this trial requires patients and their caregivers to give their time to participate. It illustrates the essential role of patients in advancing the science in Alzheimer’s disease.”

In addition to the amyloid findings, this study will shed important light on the relevance of mice to humans when it comes to Alzheimer’s research. Currently, mice are used as the screens for all Alzheimer’s drugs, but researchers do not have a clear sense of their predictive value in humans.

Also, if amyloid levels increase in the blood while also decreasing in the brain, these findings will tell researchers how the drug works to transport amyloid across the blood-brain barrier, which could be helpful not only in Alzheimer’s research but in many other areas of neurological research. Being able to permeate the blood-brain barrier is a common challenge in brain drug development.

“We know that bexarotene removes amyloid from the brain by transporting it across the blood-brain barrier, which is an unusual means that hasn’t been studied much,” said Dr. Cummings. “If the trial tells us how this works, then we can develop drugs that use the same mechanism but are less toxic than a cancer drug.”

This trial is an example of a repositioning project, where researchers take an approved drug and study it in a new use or condition. Repositioning studies are designed to accelerate the drug development process and reduce the need to constantly invent new drugs when current treatments could be used in new ways. The Center plans to look at repositioning other drugs to test them in patients with neurocognitive disorders in the near future.

For more information on this trial and the Cleveland Clinic Lou Ruvo Center for Brain Health, call 702.685.7073, visit or email

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S.News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. About 2,800 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. Cleveland Clinic Health System includes a main campus near downtown Cleveland, eight community hospitals and 18 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and, currently under construction, Cleveland Clinic Abu Dhabi. In 2010, there were 4 million visits throughout the Cleveland Clinic health system and 167,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at Follow us at

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