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Arthritis

Rheumatoid Arthritis Therapy Effective in Mice

By Emma Hitt, PhD

NEW YORK, Jan 03 (Reuters Health) - Japanese researchers have found a

way to decrease the severity of rheumatoid arthritis (RA) symptoms in mice,

and their findings may suggest an approach to treating the disease in

humans, they conclude.

In RA, the immune system attacks the lining of the joints, causing

pain, stiffness and inflammation that can lead to joint destruction and

disability. The disease usually strikes in middle age and targets women more

often than men. There is no known cure.

An immune system substance called interleukin-6 (IL-6) is thought to

play a key role in triggering the inflammation seen in RA. To investigate

potential ways to treat the disease, Dr. Akihiko Yoshimura of Kyushu

University in Fukuoka, Japan and colleagues investigated the actions of IL-6

and specific ways to block these actions.

Using mice with artificially induced RA, Yoshimura and colleagues

tested whether two types of gene therapy were able to reduce inflammation in

the animals' ankle joints.

One of the two genes they used, called CIS3, is known to block IL-6 in

living systems. The researchers wanted to see if increased amounts of this

gene introduced into mice would do the same.

The other gene they tested is a mutant form of a gene called STAT3,

which when functioning properly carries out the actions of IL-6. Yoshimura

and colleagues hoped the mutant form would interfere with these actions.

To " deliver " the two genes into the cells of the mice, the researchers

inserted each of the genes into the DNA of an adenovirus, which they then

injected into the mice.

The investigators found that delivery of the CIS3 gene into the joints

of mice " drastically reduced the severity of arthritis and joint swelling

compared with control groups " and was more effective in reducing

inflammation than the mutant STAT3 gene.

" Gene transfer of the CIS3 gene is a promising means of preventing

arthritic bone destruction, " the researchers conclude in a recent issue of

the Journal of Clinical Investigation, and " represents a novel therapeutic

strategy for preventing joint destruction associated with RA. "

According to Yoshimura, adenovirus has been used previously as a

delivery system for gene therapy, and its safety has been established. But

he pointed out that adenovirus can trigger an immune reaction after constant

use and cannot be used repeatedly.

" We wish to find small molecules or drugs that can mimic (the actions

of this gene therapy), " Yoshimura told Reuters Health.

He pointed out that many trials of RA treatment are under way

worldwide. Therapy directed toward inhibiting the actions of another

substance called tumor necrosis factor (TNF), which like IL-6 is involved

with RA symptoms, has shown " great success, " he added.

" I believe we can conquer RA completely in the near future, " Yoshimura

concluded.

SOURCE: Journal of Clinical Investigation 2001;108:1781-1788.

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