A University of Nebraska Medical Center College of Dentistry researcher
has received a three-year, $274,000 grant from the National Multiple Sclerosis
Society to evaluate whether a drug well-known for its cholesterol-lowering
effects may stop the destructive process of multiple sclerosis.
Kalipada Pahan, Ph.D., associate professor of biochemistry, is principal
investigator of the grant that will evaluate the effect of Gemfibrozil
on the disease process in mouse models. The drug, also known as Lopid,
is a safe and popular Food and Drug Administration (FDA)-approved drug
that lowers cholesterol.
MS is thought to be an autoimmune disease that affects the central nervous
system (CNS), which consists of the brain, spinal cord and the optic nerves.
Surrounding and protecting the nerve fibers of the CNS is a fatty tissue
called myelin, which helps nerve fibers conduct electrical impulses.
When theres inflammation in the brain, nitric oxide is produced and
destroys or damages myelin or the nerve fiber, affecting the ability of
the nerves to conduct electrical impulses, Dr. Pahan said. The result
produces symptoms of MS. The drug inhibits the production of nitric oxide.
In earlier studies, Dr. Pahan showed gemfibrozil inhibits the expression
of nitric oxide and the production of excessive nitric oxide in brain cells,
suggesting that the drug may inhibit the disease process of MS.
We hope the drug ultimately will be effective in people. Weve already
proven in the lab that the drug has an anti-inflammatory property. Now
we want to know if it works in mouse models. Dr. Pahan said if the study
is successful, researchers will pursue a clinical study in humans.
So far, theres only one drug available. However, it is expensive and
has a lot of side effects, such as causing a reaction from a weekly injection
and is only 30 to 40 percent effective in patients, he said. Even if
we can find a drug thats 50 percent less expensive and 50 percent more
effective, that would be better.
Dr. Pahans work focuses on studying a variety of anti-inflammatory
drugs that might stop the MS disease process.
In the April issue of the Journal of Immunology, Dr. Pahans research
team published results showing sodium phenylacetate and sodium phenylbutyrate,
two FDA-approved drugs for certain disorders in children, effectively block
symptoms of the disease process of MS in mice.
These two drugs are safe and have several advantages over interferon-b,
the approved drug for MS, Dr. Pahan said. These drugs are fairly nontoxic
and less expensive compared to interferon-b. Instead of taking painful
interferon injections, patients may be able to take these drugs orally
through drinking water or milk.
Dr. Pahan said he is motivated to do research on multiple sclerosis
because it affects people in the prime of life.
This disease affects young people just starting their careers and family
lives. There is no other disease in the world that specifically targets
young people like this. This is the frustrating part of this disease,
Dr. Pahan said.
Although the disease is not fatal, it causes weakness, tremors, loss
of vision, cognitive changes, depression and other problems. About half
of patients become wheelchair bound within 15 years of disease onset and
during the last stages of the disease, patients are bedridden. In Nebraska,
about 110 to 140 cases per 100,000 people occur, according to the National
Multiple Sclerosis Society. An estimated 1,600 to 1,800 Nebraskans have
MS.
According to the National Multiple Sclerosis Society, about 400,000
people in the United States have multiple sclerosis, which is often diagnosed
between age 20 and 40. It is more common among caucasians, particularly
those of northern European ancestry, and is more common in women than in
men. Some of the potential causes of the disease are believed to be viruses,
as well as environmental, genetic, and immune system factors.