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 society’s 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.”
What is IL-12?
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 MS 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 don’t always work out in the clinic.”
Long-term goals
The team’s 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 various effects of drugs on IL-12.
“If we can figure out with pharmaceuticals how to inhibit IL-12 gene transcription factors, then maybe we’re 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.”
What is 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 severe — paralysis 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. 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, Dr. Petro said.
Other members of Dr. Petro’s team include Eric Fung, Ph.D., Jutta Kollet, Ph.D., graduate student, and Junu Ohja, graduate student.