Researchers at the University of Nebraska Medical Center College of
Dentistry in Lincoln have received a $1 million grant to study whether
a protein present in large amounts in mice with multiple sclerosis affects
the disease process. If they are right, their discovery may lead to prevention
and better drug treatments for multiple sclerosis in humans.
Kalipada Pahan, Ph.D., assistant professor, department of oral biology
and a neuroimmunologist, is principal investigator of the four-year grant
from the U.S. Department of Health and Human Services.
Dr. Pahan and his colleagues are studying NF-kB, a protein naturally
found in the body. Researchers have found when multiple sclerosis is present
in animals, the amount of NF-kB markedly increases in the brain and spinal
cord.
Multiple sclerosis is a disease of the white matter of the brain and
spinal cord that affects the central nervous system. In multiple sclerosis,
a complex inflammatory process destroys myelin which enables nerves to
carry out their function. When myelin is destroyed, the brain and spinal
cord lose the ability to transmit signals.
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 will occur, according to the
National Multiple Sclerosis Society. An estimated 1,600 to 1,800 Nebraskans
have MS.
UNMC researchers are studying NF-kBs potential role in the multiple
sclerosis disease process through laboratory mice models called experimental
allergic encephalomyelitis, or EAE, which allow studying of the immunology
and treatment of MS. They are trying to understand how the disease process
originates.
Dr. Pahan said too much NF-kB stimulates the production of cytokines
and nitric oxide within the brain and spinal cord. Once they are produced
in excessive amounts, they become toxic and kill myelin, a protector of
nerve cells.
We find huge amounts of NF-kB in the spinal cord and the brain when
the mouse gets MS, Dr. Pahan said. Further, if we give a drug called
pyrrolidine dithiocarbamate, which prevents the production of NF-kB, the
disease process of multiple sclerosis is stopped in animals. This tells
us that NF-kB is involved in the disease process.
Currently, there is no effective treatment for multiple sclerosis, said
Dr. Pahan. Basteron, one of several available treatments, must be injected
two to four times a day. The painful injections often cause a rash at the
injection site. Flu-like symptoms are common, as well as some depression
and other side effects.
The ultimate goal of Dr. Pahans team is to find a more effective drug
that can stop the multiple sclerosis disease process in humans and cause
fewer side effects.
Recently, Dr. Pahan found that lovastatin, a non-toxic, well-established
drug that controls cholesterol, and sodium phenylacetate, another non-toxic
compound being tested for cancer treatment, stop NF-kB in brain cells.
He is trying to determine if the two compounds can stop the disease process
in laboratory animals, as well as in humans.
This disease affects young peoples lives, their family, their productivity,
just when theyre beginning their life, their career, their family, Dr.
Pahan said. I hope we can pinpoint the cause of the disease and develop
better drugs that will stop the progress of MS or prevent it entirely.
Life expectancy for people with MS has steadily improved. In 1890, the
disease was treated with herbs and bedrest, and life expectancy was five
years, according to the NMSS. By 1970, life expectancy rose to about 32
years, and today, people have a normal life expectancy.
Nationwide, it is estimated 250,000 to 350,000 people 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.