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UPTON, NY - The search for clues about multiple sclerosis (MS)
-- a chronic, often disabling disease of the brain and spinal cord
-- got a significant boost today when the National Multiple Sclerosis
Society awarded a $613,687 grant to scientists at the U.S. Department
of Energy's Brookhaven National Laboratory. The grant will support
a three-year study using Brookhaven's powerful magnetic resonance
imaging (MRI) scanner to look for early signs of disease.
"With Brookhaven's high-field magnetic
scanner, we'll be able to detect quantitative changes in the brain
at an earlier stage, and hope to learn more about the disease
process," said William Rooney, the chemist leading the study.
More than twice as powerful as a typical hospital scanner, the
Brookhaven MRI machine will allow scientists to search for subtle
changes in blood vessels that precede MS disease activity. Understanding
these changes could lead to more effective diagnosis and treatment.
MS is characterized by scarlike lesions
in the brain and spinal cord. It can lead to a range of symptoms
from mild numbness to severe paralysis or loss of vision. Each
year, approximately ten thousand new cases - about one an hour
- are diagnosed.
Scientists believe that an early step
in lesion formation is an influx of water into the brain via leaky
cerebral blood vessels. When that happens, the body's immune cells
attack the insulation surrounding nerve cells, leaving them less
able to transmit electrical signals. The leaky blood vessels may
reseal, but the multiple scars, for which the disease is named,
remain.
"The question we want to ask,"
says Rooney, is: "Is there anything different about this
tissue that we can detect before the lesion appears?"
The current study will make detailed
measurements of water content across all areas of the brain in
MS patients and control subjects. Earlier studies have shown increased
water in the brains of MS patients as compared to normal controls,
and in brain tissue that goes on to develop MS lesions as compared
to brain tissue that doesn't.
"We'll be looking for the microvascular
changes that may lead to this large and transient influx of water,"
Rooney says.
Study subjects will first be injected
with a paramagnetic contrast agent that interacts with water in
a way that makes the water more visible and quantifiable by the
scanner. By taking multiple scans over a few hours, the scientists
will follow how the contrast agent - and therefore also fluid
- is transported out of the brain's blood vessels and into the
brain tissue. (The agent washes out of the brain and body shortly
after the examination.)
In normal subjects, the so-called blood-brain
barrier lining the brain's blood vessels insures that the brain
stays tightly sealed, to maintain stable volume and keep toxic
substances out of this vital organ. But the scientists suspect
that water and other substances move more easily across the blood-brain
barrier in MS patients.
The scientists will re-examine the subjects
each month to look for changes over time, and follow the development
of MS lesions to see if they can be correlated with the brain's
permeability to the contrast agent.
Are the patients with the leakiest blood
vessels more likely to have more lesions? Is the blood-brain barrier
leaky over the entire brain, or just in the regions where lesions
form? Are people with "leaky" vessels more susceptible
to the disease? These are just some of the questions Rooney hopes
to answer.
Researchers may also use the technique
to learn whether any of the drugs currently used to treat MS might
reverse blood-vessel leakiness and possibly prevent the formation
of lesions.
The study will be done in collaboration
with Patricia Coyle, Medical Director of the MS Center at the
State University of New York at Stony Brook. She will recruit
approximately 25 patients with relapsing-remitting MS, the most
common form of the disease, and 25 normal control subjects.
"Through this work, we will improve
our understanding of the MS disease process," says Rooney,
"and help determine the feasibility of extending these techniques
to the study of other disease states, such as Alzheimer's, brain
tumors, and even human immunodeficiency virus [HIV]."
The U.S. Department of Energy's Brookhaven
National Laboratory creates and operates major facilities available
to university, industrial and government personnel for basic and
applied research in the physical, biomedical and environmental
sciences and in selected energy technologies. The Laboratory
is operated by Brookhaven Science Associates, a not-for-profit
research management company, under contract with the U.S. Department
of Energy.
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Note to local editors: William Rooney
lives in Miller Place, New York.
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