UCSF researchers have identified a correlation between higher levels of glutamate, which occurs naturally in the brain as a byproduct of metabolism, and greater disease burden in multiple sclerosis patients.
The study is the first to measure glutamate toxicity in the brain over time and suggests an improved method for tracking the disease and predicting its course.
The research team employed a novel technique, developed by Radhika Srinivasan, PhD, study author and assistant researcher in the UCSF Department of Radiology and Biomedical Imaging, to measure glutamate levels in clinical trial patients. The technique was based on a sophisticated form of imaging known as proton MR spectroscopy, which uses simple radio-frequency pulses targeting specific brain chemicals.
Study findings were presented (April 29, 2009) during the American Academy of Neurology annual scientific meeting in Seattle.
Glutamate, a neurotransmitter, in normal levels performs fundamental processes like memory and sensory perception. In excess, it triggers a cascade of negative reactions in the brain leading to many of the complications associated with neurologic diseases such as MS, Parkinson's disease, stroke, ALS (amyotrophic lateral sclerosis or Lou Gehrig's disease) and Alzheimer's disease by destroying nerve cells and causing seizures, injury after stroke, and the perception of pain, among other problems.
Already a target for therapeutic drug development, the identification of the glutamate pathway for MS suggests a new way for clinicians to monitor treatment of these drugs.
"This is the first time that we have had the ability to measure glutamate toxicity in the brain in real time, which gives us a marker for monitoring disease progression as well as our treatment of the disease," said Daniel Pelletier, MD, study author, associate professor of neurology and a member of the Multiple Sclerosis Research Group at the University of California, San Francisco.
"For instance, we already have anti-glutamate drugs, so now we can assess, with imaging, the impact of the therapy and the progression of the disease," he said.