Antioxidant drug knocks down multiple sclerosis-like disease in mice
12/26/13 Portland, Ore.
Researchers at Oregon Health & Science University have discovered that an antioxidant designed by scientists more than a dozen years ago to fight damage within human cells significantly helps symptoms in mice that have a multiple sclerosis-like disease.
The antioxidant — called MitoQ — has shown some promise in fighting neurodegenerative diseases. But this is the first time it has been shown to significantly reverse an MS-like disease in an animal.
The discovery could lead to an entirely new way to treat multiple sclerosis, which affects more than 2.3 million people worldwide.
Multiple sclerosis occurs when the body's immune system attacks the myelin, or the protective sheath, surrounding nerve fibers of the central nervous system. Some underlying nerve fibers are destroyed. Resulting symptoms can include blurred vision and blindness, loss of balance, slurred speech, tremors, numbness and problems with memory and concentration.
The antioxidant research was published in the December edition of Biochimica et Biophysica Acta Molecular Basis of Disease. The research team was led by P. Hemachandra Reddy, Ph.D., an associate scientist in the Division of Neuroscience at OHSU's Oregon National Primate Research Center.
To conduct their study, the researchers induced mice to contract a disease called experimental autoimmune encephalomyelitis, or EAE, which is very similar to MS in humans. They separated mice into four groups: a group with EAE only; a group that was given the EAE, then treated with the MitoQ; a third group that was given the MitoQ first, then given the EAE; and a fourth "control" group of mice without EAE and without any other treatment.
After 14 days, the EAE mice that had been treated with the MitoQ exhibited reduced inflammatory markers and increased neuronal activity in the spinal cord — an affected brain region in MS — that showed their EAE symptoms were being improved by the treatment. The mice also showed reduced loss of axons, or nerve fibers and reduced neurological disabilities associated with the EAE. The mice that had been pre-treated with the MitoQ showed the least problems. The mice that had been treated with MitoQ after EAE also showed many fewer problems than mice who were just induced to get the EAE and then given no treatment.
"The MitoQ also significantly reduced inflammation of the neurons and reduced demyelination," Reddy said. "These results are really exciting. This could be a new front in the fight against MS.”
Even if the treatment continues to show promise, testing in humans would be years away. The next steps for Reddy's team will be to understand the mechanisms of MitoQ neuroprotection in different regions of the brain, and how MitoQ protects mitochondria within the brain cells of the EAE mice. Mitochondria, components within all human cells, convert energy into forms that are usable by the cell.
There is a built-in advantage with MitoQ. Unlike many new drugs, MitoQ has been tested for safety in numerous clinical trails with humans. Since its development in the late 1990s, researchers have tested MitoQ's ability to decrease oxidative damage in mitochondria.
“It appears that MitoQ enters neuronal mitochondria quickly, scavenges free radicals, reduces oxidative insults produced by elevated inflammation, and maintains or even boosts neuronal energy in affected cells,” said Reddy. The hope has been that MitoQ might help treat neurodegenerative diseases like Alzheimer's and Parkinson's. Studies evaluating its helpfulness in treating those diseases are ongoing.
Peizhong Mao, Ph.D., assistant professor of physiology and pharmacology in the OHSU School of Medicine, Maria Manczak, Ph.D., a research associate at ONPRC, and Ulziibat Shirendeb, Ph.D., a former postdoctoral scientist at ONPRC, are co-authors on Reddy’s study.
The research was funded by the National Institutes of Health (grants AG028072, AG042178 and RR000163) – and a grant from Vertex Pharmaceuticals.
The ONPRC is one of the eight National Primate Research Centers supported by NIH. ONPRC is a registered research institution, inspected regularly by the United States Department of Agriculture. It operates in compliance with the Animal Welfare Act and has an assurance of regulatory compliance on file with the National Institutes of Health. The ONPRC also participates in the voluntary accreditation program overseen by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).
Oregon Health & Science University is a nationally prominent research university and Oregon’s only public academic health center. It serves patients throughout the region with a Level 1 trauma center and nationally recognized Doernbecher Children’s Hospital. OHSU operates dental, medical, nursing and pharmacy schools that rank high both in research funding and in meeting the university’s social mission. OHSU’s Knight Cancer Institute helped pioneer personalized medicine through a discovery that identified how to shut down cells that enable cancer to grow without harming healthy ones. OHSU Brain Institute scientists are nationally recognized for discoveries that have led to a better understanding of Alzheimer’s disease and new treatments for Parkinson’s disease, multiple sclerosis and stroke. OHSU’s Casey Eye Institute is a global leader in ophthalmic imaging, and in clinical trials related to eye disease.