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The University of Texas at San Antonio Online Magazine

Seeking Solutions, Delivering Hope

Researcher’s passion for science and compassion for people drive MS research

Thomas Forsthuber was a medical student in his first neurology course when the plight of multiple sclerosis patients struck him. Of all the diseases that he studied, this one seemed especially unkind. It arose mysteriously in the prime of life, causing the body’s own immune system to turn hostile and wage war on the delicate protective layers that surround brain cells. And it seemed there was little that doctors could do as this stealth attack began to fray the circuits in the brain, causing vision problems, muscle weakness, loss of coordination, pain and numbness. In the most serious cases, the disease stole away patients’ ability to walk or speak.

"I vividly remember that lecture," Forsthuber said of the class he attended two decades ago at the University of Tubingen, Germany, where he received his M.D. and Ph.D. "They had no idea why this happened; why did the body turn against its own protective cells?"

Six years ago, Forsthuber relocated from Case Western Reserve University in Cleveland and brought those questions to UTSA, where he now is a professor of immunology. Here, his passion for science and compassion for people drive a research program that is delving into the immune system for clues about what goes wrong and what can be done to stop the devastating damage that follows.

"My weak spot is ill people, but MS patients have a special spot with me," he said. "If you have the flu, we know what we can do for you. But if you have multiple sclerosis, we don’t have a lot that we can do. Most patients go slowly downhill for 20 or 30 years. They lose their vision, their muscle control; some of them lose their families because they can’t cope.

"On the outside, they look OK, but on the inside, they are ill and suffering."

The program has been a boost to multiple sclerosis patients in the South Texas area, not just scientifically but emotionally as well. Forsthuber invites groups of them to his laboratory and he attends their fundraising functions.

"He holds out hope to a group of people who are looking for any kind of hope," said Tony Ralf, regional vice president for the Lone Star and Rio Grande chapters of the Multiple Sclerosis Society. "This is not like the scientist you see on TV who is removed from society."

Even after years of scientific probing, much about multiple sclerosis remains an enigma. Research has shown that people with a specific gene, called HLADR2, have a higher risk of developing MS. Other clues suggest there is an outside event–an injury, infection or toxic exposure—that actually brings on the disease.

"You need the perfect storm," said Forsthuber. "If you have the gene, your immune system is ready to cause this assault on your brain. But then something has to trigger it."

The insult causes the myelin sheath, an insulating layer of fat that encases the neurons, to release an antigen. The antigen somehow activates a hostile reaction in select immune cells. The body then mounts an attack, producing more and more immune cells devoted to the destruction of its own healthy tissue.

Dr. Thomas Forsthuber, professor of immunology and the Jesse H. and Mary Gibbs Jones Endowed Chair in Biotechnology, and his students are trying to unlock the mysteries of multiple sclerosis.

"They mistake the brain for something that is infectious," Forsthuber said.

With damaged myelin, brain cells misfire like faulty electrical wiring. In most patients, symptoms come and go, causing pain, numbness, fatigue, blurry or double vision and loss of muscle coordination. But the more serious forms of the disease can leave people unable to walk or talk. About 400,000 people in the United States have MS; 18,000 of them live in Texas. It usually is diagnosed between the ages of 20 and 40, and is more common in women.

For years, the only available treatments were steroid medications to suppress the immune reaction. More recently, researchers have developed drugs that work by blocking the action of specific immune cells. These are not effective in all patients, however, and some of them have potentially dangerous side effects.

Forsthuber’s work focuses on T-cell lymphocytes, a type of white blood cell that is a crucial component of the immune system attack. Using laboratory mice that have been bred to carry the human form of the HLA gene, Forsthuber has identified what piece of the myelin is vulnerable to the T-cell attack. Now he is working with a drug company to test an experimental medication that blocks the pathogenic T-cells from reaching that vulnerable spot.

He also is working to identify biomarkers—proteins circulating in the blood that can tell doctors how patients are responding to their therapy and whether some are developing resistance to the steroid medications they are taking. This is the emerging field of proteomics, or the detailed study of proteins, a research field that got a giant boost last year when UTSA landed a key federal grant.

The funding came from the National Institutes of Health, via the Research Centers in Minority Institutions (RCMI) program, which helps build research capacity at universities that serve minority student populations. UTSA is getting a $12 million infusion of capital over the next five years, much of it earmarked for the state-of-the-art equipment needed to enable cutting-edge research projects, like the ones Forsthuber is undertaking. Faculty members have access to the Proteomics and Protein Biomarkers cores, laboratories dedicated specifically to this type of research, where advanced techniques like mass spectrometry and chromatography help them identify and characterize important proteins.

This investment gives Forsthuber’s team in San Antonio the same opportunity for discovery as scientists at any top-tier biomedical research university. "I can do everything here that I would at Case Western or Harvard," Forsthuber said.

However, this is not a research project confined to the walls of a laboratory. Forsthuber, his staff and students shed lab coats and donned sneakers in February when the Multiple Sclerosis Society Lone Star Chapter held its annual fundraising walk at the AT&T Center.

The chapter also brings groups of MS patients and prospective donors to Forsthuber’s lab to learn first-hand about the work that goes on there.

"We have pretty much open access to his lab," said Ralf. "That is almost unheard of in research. He really wants to have that personal contact with the people he is trying to help."

Forsthuber thrives on the contact. The patients remind the scientists and students in his lab about the human need that drives their work, Forsthuber said.

"I love the process of discovery," he said. "But I also have a big soft spot for people who are ill."

–Cindy Tumiel


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