Cleveland Clinic Lou Ruvo Center for Brain Health Leads Ground-breaking Drug Trial for Alzheimer’s Disease
By Jeffrey Cummings, MD, ScD
The anti-cancer drug bexarotene was observed to have dramatic impact on the protein of Alzheimer’s disease in mice genetically engineered to have increased amounts of this protein in their brains. Bexarotene produced a 50 percent decrease in protein levels in one week, and was associated with improvements in measures of mouse behavior.
Bexarotene is unique in that it is already approved for the treatment of skin cancer and has been widely used in elderly individuals. “Repurposing” approved drugs is a great advantage because the safety of the treatments has already been established.
I joined with Kate Zhong, MD, Director of the Lou Ruvo Center for Brain Health’s Clinical Trials Program, to design a human clinical trial as soon as the results of the mouse experiment were published. After review by the FDA and identification of support from generous donors, 20 patients were recruited to a one-month, double-blind, placebo-controlled trial, followed by a one-month extension during which all patients were treated with bexarotene. The results of the intervention were interpreted according to whether patients had a specific gene thought to influence the effects of the therapy.
Remarkably, in individuals without the risk gene, there was a marked reduction in the brain Alzheimer protein content. There was also a correlated increase in the blood level of the Alzheimer protein, suggesting that the protein was effectively being removed and exported into the blood stream, where it could be removed from the body. As anticipated given the short treatment period, there was no corresponding improvement in memory or thinking in the patients.
The critical observation in this study is that in a genetically defined subgroup of patients with Alzheimer’s disease, bexarotene produced a significant lowering of brain Alzheimer protein content. There was a correlated increase in the blood level of the protein. This biological effect supports the further study of bexarotene as a possible treatment for Alzheimer’s disease. Longer treatment may result in clinical as well as biological benefit. The Lou Ruvo Center for Brain Health is unique in having studied this drug and, possibly, in opening a new pathway for the treatment of Alzheimer’s disease; our work was published in 2016 in Alzheimer’s Research & Therapy.
About the author:
Jeffrey Cummings, MD, ScD, is Director of the Lou Ruvo Center for Brain Health. Ranked the sixth-most prolific Alzheimer’s researcher by the Journal of Alzheimer’s Disease, he is the author of 40 books and more than 650 peer-reviewed articles. He is a respected clinician, a neuroscientist with expertise in clinical trials and drug development, and a forward-thinking strategist concerning how to deliver optimal care to the growing number of patients with neurodegenerative disorders. He has expertise in clinical trial design and analysis, global trial implementation and trial outcome measures, and has been recognized with the Alzheimer’s Association Research Award.
About Us
Cleveland Clinic Lou Ruvo Center for Brain Health provides state-of-the-art care for patients with Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, frontotemporal dementia, multiple system atrophy and multiple sclerosis. The center provides “patients first” care, support for caregivers and family members, and clinical trials to advance new therapies for neurological disorders. More information: www.clevelandclinic.org/brainhealth
We are located in Las Vegas, Nevada. Contact us:
To make a medical appointment: 702-483-6000
To participate in a clinical research: 855-LOU-RUVO
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