Georgetown University Medical Center (GUMC
Jan. 29, 2016
In laboratory neuronal cultures, an FDA-approved drug used to treat high blood pressure reduced cell damage often linked to Alzheimer's disease, say researchers at Georgetown University Medical Center (GUMC) and the National Institutes of Health.
They say their work, published online Jan. 28 in the journal Alzheimer's Research and Therapy, provides information supporting the potential effect of the drug candesartan - as well as other Angiotensin receptor blockers (ARBs) for the early treatment of Alzheimer's disease.
"Our findings make sense in many ways," says the study's senior author Juan M. Saavedra, MD, from GUMC's Department of Pharmacology and Physiology. "Hypertension reduces blood flow throughout the body and brain and is a risk factor of Alzheimer's disease. Previous epidemiological studies found that Alzheimer's progression is delayed in hypertensive patients treated with ARBs."
Using neuronal cultures, the researchers explored the action of candesartan on the neurotoxic effects of exposure to excessive glutamate, a demonstrated injury factor in the early stages of Alzheimer's disease.
The scientists found that candesartan prevented glutamate-induced neuronal death. They conducted in-depth gene analyses of the laboratory results, demonstrating that candesartan prevented neuronal inflammation and many other pathological processes, including alterations in amyloid metabolism, a hallmark of Alzheimer's disease.
The study's first author, Abdel G. Elkahloun, PhD, from the Comparative Genomics and Cancer Genetics Branch of the National Human Genome Research Institute, then compared gene expression in the neuronal cultures with published gene databases of autopsy samples from Alzheimer's disease patients. "The correlations were impressive - the expression of 471 genes that were altered by excess glutamate in our cultures were also altered in brain autopsy samples from patients who suffered from Alzheimer's disease. Candesartan normalized expression of these genes in our cultures," Elkahloun says.
"We hypothesize that candesartan, or other members of the ARB group, may not only slow progression of Alzheimer's but also prevent or delay its development," Saavedra says.
The researchers say this work has immediate translational value, supporting testing candesartan, or other ARBs, in controlled clinical studies on patients at early stages of Alzheimer's disease.
Roman Hafko, PhD, formerly of the National Institute of Mental Health, also contributed to this work and is an author of the paper.
The work was supported by grants from the National Institutes of Health including the National Human Genome Research Institute (MD 20892) and the National Institute of Mental Health (MH 002762-16). The authors report having no personal financial interests related to the study.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health.