Natural Compounds Block Autoimmune Response In Diabetes, Arthritis

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November 7, 2006

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Natural Compounds Block Autoimmune Response In Diabetes, Arthritis

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.



Sea anemone. (Image courtesy of University of California - Irvine)

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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

Chandy and 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, is a co-lead author,

and other authors from UCI, UC , s 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 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.

http://www.sciencedaily.com/releases/2006/11/061107082647.htm