In lab and mice studies, compound halts disease without crimping immune system
THURSDAY, June 4 (HealthDay News) -- A compound derived from hydrangea root, an herb used in traditional Chinese medicine, halted the progression of an autoimmune disorder in laboratory mice and human cells, new research shows.
What makes the compound, halofuginone, so promising, the researchers said, is that it slowed progression of the disease without suppressing normal immune system functioning.
A major drawback to current treatments for autoimmune disease is increased risk for infections because of suppressed immune system functioning, according to the study, which appears in the June 5 issue of Science.
"This is really the first description of a small molecule that interferes with autoimmune pathology but is not a general immune suppressant," said the study's lead study author, Mark Sundrud, from the cellular and molecular medicine program and the Immune Disease Institute at Children's Hospital Boston.
Autoimmune diseases occur when the immune system mistakenly attacks and destroys healthy tissues and organs.
The disorders, which include multiple sclerosis, lupus and rheumatoid arthritis, are difficult to treat because drugs that can suppress inflammatory attacks by the immune system on body tissues often have the side effect of suppressing the functioning of the immune as well.
Other current treatments include intravenous infusions of antibodies that neutralize cytokines, the chemical messengers produced by T cells that regulate immune function and inflammatory responses.
But the antibodies are expensive and don't stop the production of cytokines, the root cause of disease, according to the study. People must receive frequent infusions to keep inflammation in check.
Previous research has implicated Th17 cells in a variety of autoimmune disorders, including inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, eczema and psoriasis.
In the study, researchers gave halofuginone to mice with experimental autoimmune encephalitis (EAE), an artificially induced immune disease that resembles multiple sclerosis in humans.
They found that low-doses of halofuginone inhibited the development of Th17 cells in the mice but did not alter other kinds of T cells important for normal immune function.
Tests in human cells in the lab showed a similar inhibition of Th17 cell formation.
The researchers believe that halofuginone acts by activating a biochemical pathway known as the amino acid starvation response, or AAR, which typically protects cells when amino acids, the essential building blocks of proteins, are in short supply.
When excess amino acids were added to cultured T cells that were exposed to halofuginone, the AAR didn't switch on, allowing Th17 cells to develop.
Conversely, the researchers were able to inhibit Th17 differentiation by depleting amino acids and causing the AAR to kick in.
"When a cell senses amino acid deprivation, it tries to conserve amino acids by preventing specific types of responses that are energetically expensive," Sundrud said. "In inflamed tissues, a lot of cells are producing a lot of protein, so it would make sense that a cell with amino acid deprivation would want to block signals that promote inflammation."
Halofuginone is one of the 50 "fundamental herbs" of traditional Chinese medicine, according to the study. It has also been used as an anti-malarial agent. Decades ago, according to background information in the news release, the U.S. Army tried to improve upon its anti-malarial properties without success.
Halofuginone is also used to treat scleroderma, an autoimmune disease of the connective tissue. Because the compound is now in the public domain, the pharmaceutical industry has not shown interest in further developing it therapeutically, researchers said.
But halofuginone or some yet-to-be developed derivative compound could potentially be used to address any autoimmune or inflammatory disease related to Th17 cells, researchers said.
The American Autoimmune Related Diseases Association has more on autoimmune disorders.
-- Jennifer Thomas
SOURCE: Children's Hospital Boston, news release, June 4, 2009
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