Novato, CA and Bedford, MA, November 1, 2001 – Neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease may be attenuated through the use of certain drugs, known as synthetic catalytic scavengers of reactive oxygen species (SCSs), that powerfully augment natural anti-oxidant systems, scientists reported in the November 2001 issue of the Journal of Neuroscience. The report details experiments in which treatment with SCSs rescued a severe neurological phenotype in mice engineered to undergo a specific form of oxidative damage. Treatment with the SCSs also resulted in a dramatic enhancement of lifespan of the mice.
The research contained in the report was conducted through a collaboration among scientists at the Buck Institute for Age Research (Novato, CA), Eukarion, Inc. (Bedford, MA) and others.
The studies utilized mice that lack a form of superoxide dismutase (SOD2), a natural anti-oxidant enzyme found in the mitochondria. The mitochondria essentially serve as the powerplant of the cell, utilizing oxygen and nutrients to generate the energy that is critical to cellular functions. As a byproduct to this key process, known as oxidative metabolism, the mitochondria also produce potentially damaging reactive oxygen species and, hence, the mitochondria’s own antioxidant defenses are extremely important. Oxidative damage to the mitochondria has been implicated in several neurodegenerative diseases and disorders, including Parkinson’s and Alzheimer’s diseases, amyotropic lateral sclerosis (ALS), Freidrich’s ataxia, and aging.
Previous studies showed that mice lacking SOD2 undergo oxidative damage to the mitochondria and, concomitantly, suffer a variety of severe pathologies in many tissues. Untreated, these mice live for approximately one week. Treated with an antioxidant that does not gain access to the brain, the mice live longer, but develop a lethal neurological disorder. This disorder, a spongiform encephalopathy, involves widespread pathological damage to the brain and profound motor disturbances.
In the Journal of Neuroscience study, mice lacking SOD2 were treated with three different SCSs. The SCSs are proprietary compounds developed by Eukarion that mimic the naturally occurring cellular antioxidant enzymes SOD and catalase. These antioxidant enzymes normally work together to protect cells and tissues from damage due to oxidative stress. The study showed that treatment with each of the SCSs dramatically enhanced survival of the mice, increasing their lifespan to greater than three-fold that of untreated mice. In addition, SCS treatment rescued the spongiform neurodegenerative disorder, demonstrating that the SCSs crossed the blood-brain barrier and gained access to the mitochondria, the main site of oxidative stress.
“These studies are important and relevant to human diseases,” said Simon Melov, Ph.D., a founding faculty member of the Buck Institute. “They clearly demonstrate, in a mammalian system, the link between a build-up of mitochondrial oxidative stress and the development of severe neurodegeneration with potential relevance to several age-related degenerative diseases. Further, they build on previous studies we published which showed a significant extension of life span in the nematode worm C. elegans through treatment with SCSs, now extending key elements of those earlier findings to mammals.”
“These new results also build upon our earlier research in models for neurological disorders such as stroke and ALS, demonstrating clearly that SCSs cross the blood-brain barrier and protect the brain mitochondria from oxidative damage,” said Susan R. Doctrow, Ph.D., Eukarion’s Vice President, Research, “In particular, the most effective compound in the study, EUK-189, was designed for enhanced cellular and brain permeability. We are working to advance SCSs such as EUK-189 toward clinical development for treatment of a potentially broad range of degenerative, age-related conditions.”
About the Buck Institute for Age Research
The Buck Institute is a non-profit organization that conducts biomedical research into the basic mechanisms of aging and of age-related diseases such as cancer, stroke and Alzheimer’s. Its mission is to extend the healthy, productive years of life through clinically relevant basic research. The Buck Institute has brought together a multi-disciplinary group of researchers, and state-of-the-art technologies and resources, to focus on the complex challenge of discovering why we develop diseases as we age and developing therapeutics to prevent these debilitating conditions. The Buck Institute for Age Research, located 20 miles north of San Francisco, California, is the only institute of its kind in the United States, and just three such institutes world-wide. For more information, please visit www.buckinstitute.org.
About Eukarion, Inc.
Eukarion, Inc., a privately held biopharmaceutical company located in Bedford, MA, is developing small molecule drugs primarily for the treatment of degenerative and age-related disorders. The company’s principal focus is on its patented synthetic catalytic scavenger (SCS) technology for the treatment of conditions associated with oxidative stress. In addition to its SCS technology, Eukarion is developing proprietary technology to adapt monoclonal antibodies for intracellular use. For more information, visit www.eukarion.com.
Bernard Malfroy, Ph.D.
Janet Smart, Ph.D.
Buck Institute for Age Research: