"There's a straightforward message from this: This peptide treatment stops the assault of autoimmune disease by preventing immune-cell interactions," said Caroline C. Whitacre, professor and chair of molecular virology, immunology and medical genetics at The Ohio State University College of Medicine and Public Health.
The study appears in the Aug. 15 issue of the Journal of Immunology.
In mice, the peptide was able to inhibit experimental autoimmune encephalomyelitis (EAE), an autoimmune disease in animals that closely resembles multiple sclerosis in humans.
"Even after the disease is ongoing, a single administration of the peptide suppresses the disease," Whitacre said. "We don't know yet if this treatment will be effective for MS, but the implication is that administering this peptide to a patient with active disease could make that patient better."
This represents the second phase of a multiphase project at Ohio State to develop the peptide, describe its interactions with T cells and investigate how it works to suppress disease. A report released last year in the Journal of Immunology from these researchers described the chemical properties of the peptide and the innovative aspects of the design of the peptide mimic.
T cells - white blood cells involved in causing some autoimmune diseases like MS - require two signals during activation and development of an immune response. First, a receptor on the surface of a T cell recognizes a cell carrying the disease-causing antigen. Second, the CD28 molecule on a T cell recognizes the CD80 molecule on the cell containing the antigen. The peptide - a specially engineered fragment of the CD28 molecule - binds to CD80, interfering with the interaction necessary for the activation of the T cell. The peptide was developed at Ohio State by cancer researcher Pravin Kaumaya and graduate student Mythily Srinivasan.
Researchers predict that by preventing the T cell from getting the second signal it needs to begin its attack, the peptide in effect kills the T cell and halts expansion of active disease.
"Increasing the number of specific white blood cells is one of the major goals of the immune system. Once T cells are exposed to their specific antigen, that expands the cell population," Whitacre said. "In the case of autoimmune diseases, however, expansion of lymphocytes directed against self antigens is detrimental to the host. In cases where immune cells attack the host, the death of a T cell is a desirable outcome."
In both EAE and multiple sclerosis, immune cells attack the myelin sheath surrounding nerves in the brain and spinal cord. This leads to weakness, loss of coordination and other neurological problems that characterize these diseases. MS, a chronic condition that typically strikes young adults, is characterized by a remitting-relapsing pattern of attack in the majority of MS patients.
About 300,000 people are diagnosed with MS in the United States. There is neither a single known cause nor a universally effective treatment for the disease, which has been documented for 130 years.
Kaumaya, professor of obstetrics and gynecology and microbiology and a cancer researcher in Ohio State's Comprehensive Cancer Center, is principal collaborator with Whitacre on the study. He described the Ohio State research as an early preclinical step in making progress toward application of peptide treatment in clinical trials for MS patients.
"We are also looking at its applicability in other autoimmune disease, such as in graft vs. host disease in transplantation," he said. Before clinical trials can begin, the peptide treatment must be shown to be safe and tolerable as well as being effective in studies in animals.
"We also will be looking at what is happening at the site of ongoing disease so we can mimic what happens in the body," said Whitacre, also associate vice president for health sciences research and vice dean for research in Ohio State's College of Medicine and Public Health. "We need more in-depth studies of the mechanism of disease so we can see what peptides do in the brain, at the site of the damage."
This work was supported by the National Institutes of Health and the National Multiple Sclerosis Society.
Contact: Emily Caldwell, Medical Center Communications, 614-293-3737, or email@example.com