Wednesday, November 08, 2006
UCI study identifies how treatment can limit impact of T cells in autoimmune diseases
Natural compounds derived from a sea anemone extract and a shrub plant have been found to block the autoimmune disease response in type-1 diabetes and rheumatoid arthritis, according to University of California, Irvine researchers.
The study shows both in human and animal tests how these compounds work to deter the effect of autoimmune T-cells, white blood cells that attack the body. The goal, according to UCI researchers, is to develop new treatments from these compounds that will target these destructive T-cells while allowing other white blood cells to fight disease and infection.
Study results appear Nov. 6-10 in the Early Online Edition of the Proceedings of the National Academy of Sciences.
The study, led by UC Irvine School of Medicine researchers George Chandy and Christine Beeton, identifies how these compounds work against a type of white blood cells called effector memory T lymphocytes, which play a major role in autoimmunity. Both compounds block an ion channel in these cells that prevents the cells from proliferating and producing chemicals called cytokines that attack the body during autoimmune disease states.
"Autoimmune diseases affect millions of Americans, and any new therapies that can aid them will have great significance," Chandy said. "What's promising about this study is that we identified a protein target on the T-cells that promote autoimmune activity and the compounds that can selectively block the target and shut down the destructive cells."
White blood cells patrol the body to fight against cancer and infections, but if some of these cells turn against the body they are meant to protect, they cause autoimmune diseases. Millions of people worldwide are afflicted with disabling autoimmune disorders. Two examples of this large class of diseases are type-1 diabetes, in which white blood cells attack the pancreas, and rheumatoid arthritis, in which the joints are attacked.
In their study, the UCI researchers used modified compounds derived from the rue plant (PAP-1) and a Cuban sea anemone extract (SL5), both of which block the ion channel in the destructive T-cells.
In one set of tests using blood samples from type-1 diabetes patients and joint fluid from people with rheumatoid arthritis, the researchers found that both compounds suppressed the function of the autoimmune T-cells without affecting other T-cells that fight infections.
In another set of tests using rats, the compound from the rue shrub plant delayed the onset and reduced the incidence of disease in diabetic rats, while the venom compound stopped the progression of the disease and improved the joint function of rats with experimental autoimmune arthritis. In these rat tests, the compounds were nontoxic.
The Chandy laboratory previously discovered that SL5 compound was effective in treating rats with an experimental model of multiple sclerosis, another devastating autoimmune disease. Preclinical safety studies on PAP-1 and SL5 are under way in collaboration with AIRMID, a biotech company in the San Francisco Bay Area.
"We began our work on these natural products many years ago when we came across a report that described the beneficial effect of a scorpion sting on a patient with multiple sclerosis," Beeton said. "This work also speaks to the importance of protecting our plant and animal biodiversity -- you never know where a new medicine will come from."
Heike Wulff from University of California, Davis is a co-lead author, and other authors from UCI, UC Davis, Johns Hopkins University, Bachem Biosciences and the Benaroya Research Institute in Seattle are noted in the study text. The National Institutes of Health, American Diabetes Association, Juvenile Diabetes Research Foundation, National Multiple Sclerosis Society, Arthritis National Research Foundation and David Israelsky provided support for this study.
About type-1 diabetes and rheumatoid arthritis: The American Diabetes Association estimates that type-1 diabetes mellitus, also known as juvenile diabetes, affects one in every 400 or 600 children and adolescents in the U.S. It is characterized by a destruction of the cells that produce insulin in the pancreas. Without enough insulin, the body cannot correctly regulate levels of blood glucose, a major source of energy for the body. Type-1 diabetes can lead to serious complications such as heart disease, blindness, and nerve or kidney damage.
In rheumatoid arthritis, white blood cells induce inflammation in the joints, leading to muscle and joint aches, stiffness, and fatigue. According to the Arthritis Foundation, rheumatoid arthritis is one of the most serious and disabling types, affecting mostly women. An estimated 2.1 million people in the U.S. have rheumatoid arthritis. Some recent studies have suggested that the overall number of new cases of rheumatoid arthritis actually may be going down.