Michel Baudry, PhD, dean of the Graduate College of Biomedical Sciences at Western University of Health Sciences, will publish his research on the critical role of oxidative stress in Alzheimer’s disease and a potential treatment.
The article, co-authored by College of Osteopathic Medicine of the Pacific Associate Professor Xiaoning Bi, MD, PhD, will be published in the May 2012 issue of the Journal of Alzheimer’s Disease.
Oxygen free radicals are ubiquitous because they are a consequence of the way we live – in an oxygenated environment, Baudry said. We take in oxygen to burn food in order to produce energy, which is used by cells. But in the process we leak oxygen free radicals. Cells have developed a strong defense mechanism to prevent the accumulation of these reactive oxygen species because they produce a chain reaction. If the radicals are not eliminated, they damage proteins, lipids and DNA, further increasing their production by damaging mitochondria.
The brain is very susceptible to excessive formation of reactive oxygen species. Alzheimer’s disease may create a vicious cycle with the amyloid beta peptide, a peptide presumably involved in the disease, impairing mitochondrial function, resulting in the creation of these reactive oxygen species, which then results in further cell damage.
Baudry, in collaboration with Dr. Bernard Malfroy, now CEO of MindSet Rx, Inc., discovered a series of manganese complexes, EUKn, that act like enzymes to fight reactive oxygen species. EUKn cannot be swallowed in pill form because they get destroyed in the stomach, so they must be injected.
The goal of the study was to examine whether reactive oxygen species are critically involved in Alzheimer’s disease and to test the effectiveness of one of the EUKn, EUK-207, in protecting against symptoms of the disease and progression of these symptoms.
Mice modeling human Alzheimer’s disease (AD) were treated with EUK-207 for five months starting at four months before the appearance of AD symptoms. The non-treated mice had increased oxidative stress (lipid, protein and DNA oxidation) and AD symptoms (impaired cognition and brain pathology). The treated mice had none of these markers of oxidative stress, and were protected from most of the pathology associated with Alzheimer’s disease, Baudry said.
“This suggests the increased formation of reactive oxygen species is causally related to the disease,” he said. “If you block oxidative stress, you block the appearance of the disease.”
In the second part of the study, mice were treated with EUK-207 for three months starting at nine months of age, when AD symptoms were clearly present.
“We found the treatment prevented further accumulation of oxidative stress, and significantly reduced the further progression of the pathology,” Baudry said.
The study was supported by the Alzheimer’s Association. Baudry and Dr. Malfroy are now exploring the possibility of putting EUK-207 in a clinical trial in collaboration with an undisclosed partner. Dr. Baudry said he would “love to see EUK-207 or one of its analog to be developed for the prevention and treatment of AD, as the animal results are so compelling.”
The article is slated for publication in the Journal of Alzheimer’s Disease, 30:1, which is scheduled for online publication ahead of print on May 8, 2012. An early online version: http://iospress.metapress.com/content/p4q668360856x546/?p=03f8df0dbef048e4b7a2f6f60ac6b964&pi=1
NOTES FOR EDITORS
“Effects of the Superoxide Dismutase/Catalase Mimetic EUK-207 in a Mouse Model of Alzheimer’s Disease: Protection Against and Interruption of Progression of Amyloid and Tau Pathology and Cognitive Decline.” Aaron Clausen, Xiaobo Xu, Xiaoning Bi, Michel Baudry. Journal of Alzheimer’s Disease. Volume 30, issue 1 (May 2012). DOI: 10.3233/JAD-2012-111298. Aaron Clausen is now a postdoc at UC Irvine, and Xiaobo Xu is finishing her PhD dissertation at USC.
About Western University of Health Sciences
Western University of Health Sciences (www.westernu.edu), located in Pomona, Calif. and Lebanon, Ore., is an independent nonprofit health professions university, conferring degrees in biomedical sciences, dental medicine, health sciences, medical sciences, nursing, optometry, osteopathic medicine, pharmacy, physical therapy, physician assistant studies, podiatric medicine and veterinary medicine.
About the Journal of Alzheimer’s Disease (JAD)
The Journal of Alzheimer’s Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer’s Disease has an Impact Factor of 4.261 according to Thomson Reuters’ 2011 edition of Journal Citation Reports. It is ranked #19 on the Index Copernicus Top 100 Journal List. The Journal is published by IOS Press (www.iospress.com).