Thomas Petro, Ph.D, Department of Oral Biology, UNMC College of Dentistry,
has been awarded a $209,000, three-year grant from the National Multiple
Sclerosis Society to study a cell protein called Interleukin-12 (IL-12)
to determine its role in multiple sclerosis.
The societys President and Chief Executive Officer, Mike Dugan, said
the research is a promising and difficult study in the interest of all
those who are living with multiple sclerosis.
Dr. Petro, who has been studying IL-12 for 10 years, and for the last
three years as it applies to multiple sclerosis, said despite the known
association between multiple sclerosis and the protein, there is a lack
of knowledge about how it is stimulated during the disease.
We want to know what happens in the first few hours in the cell following
its infection by a virus that causes multiple sclerosis symptoms in a mouse
model, said Dr. Petro, principal investigator of the grant.. Despite
several treatments that have been widely accepted, MS therapies have not
been developed which exploit the
signaling mechanisms that lead to the expression of key genes associated
with disease, Dr. Petro said.
Dr. Petro said all humans produce IL-12, which is a small protein produced
by macrophage cells that communicate immune system responses. In regulated
amounts, IL-12 is important in preventing many diseases, including cancer
and tuberculosis.
The problem is when excessive amounts of IL-12 are produced. Dr. Petro
hypothesizes that excess IL-12 is produced in the mouse brain following
an infection by an MS-model virus.
An excess of the protein in the brain in mouse models causes multiple
sclerosis symptoms, similar to those in humans. He and his team hope to
determine the details of the key signaling mechanism that leads to a MS-like
disease in the mouse virus model.
We expect that similar if not identical signaling mechanisms play a
role in humans, Dr. Petro said. In the mouse, if IL-12 is blocked, then
symptoms get better, but we have yet to test this in humans. This gap in
knowledge is important to fill since IL-12 expression is a feasible target
for MS therapy.
We have all the tools available to come up with an answer to exaggerated
production of IL-12. Of course, we realize sometimes things work great
in the test tube but dont always work out in the clinic.
The teams long-term goal is to inhibit or reduce the cellular activity
of IL-12 and develop therapeutic strategies for disrupting the process
so symptoms can be reduced.
If you could somehow lower the IL-12 production, the thought is that
this will help people by reducing or controlling their MS symptoms. Reducing
the IL-12 activity seems to help disease symptoms in mice, Dr. Petro said.
The way MS works is that you have an initial episode with symptoms.
Then after some time you may get better. Later you may have a recurrence
of symptoms and the symptoms may get worse. All the while you know the
symptoms will come back, he said.
Dr. Petro said he and his colleagues also will study in the laboratory,
various effects of drugs on IL-12.
If we can figure out with pharmaceuticals how to inhibit IL-12 gene
transcription factors, then maybe were on to something, then it actually
may be possible to do something at the IL-12 gene to reduce or stop symptoms
of MS. This goal is within reach because presently, several novel anti-cancer
therapies have emerged from basic research dealing with cell signaling
mechanisms. It is now time to explore similar possibilities for treatment
of MS.
Multiple sclerosis is a chronic, often disabling, disease of the central
nervous system. Symptoms may be mild, such as numbness in the limbs, or
severeparalysis or loss of vision. There currently is no cure for the
disease. Until recently, steroids were the principal medications for MS.
While steroids cannot affect the course of MS over time, they can reduce
the duration and severity of attacks in some patients.
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. According
to the National Multiple Sclerosis Society, an estimated 1,600 to 1,800
Nebraskans have MS.
The cause of MS remains elusive, but most people have a normal life
expectancy. The vast majority of MS patients are mildly affected, but in
the worst cases, MS can render a person unable to write, speak, or walk.
MS patients require lifelong medical care and rehabilitation. Each year,
MS patients incur a loss in productivity of more than $2.5 billion, said
Dr. Petro.
Other members of Dr. Petros team include Eric Fung, Ph.D., Jutta Kollet,
Ph.D., graduate student, and Junu Ohja, graduate student.