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November 4, 2002
Promising animal test results that could lead to a vaccine to fight rheumatoid arthritis, multiple sclerosis (MS) and other autoimmune diseases were announced by researchers at the Technion-Israel Institute of Technology. The vaccine reversed an arthritic-like disease in rats by mobilizing part of the immune system to protect joints under attack by other immune cells. The work was reported in two related papers in the September issue of the Journal of Immunology.
Autoimmune diseases, in which the immune system attacks the body's own tissues, are among the most widespread of serious chronic diseases. In arthritis, immune cells attack the joints, while in MS, they attack the myelin sheaths of nerve cells.
Current treatments involve either steroids, which fight inflammation caused by the immune system attacks, or immuno-suppressant drugs, which depress immune system function generally. Both these approaches create serious side effects and can only slow, but not stop, the progress of the diseases. They are also effective mostly at very early stages of each disease.
The new approach, in contrast, tries to rally one part of the immune system to fight the part that is attacking the body's tissues. "We know that, in autoimmune diseases, immune cells use chemical markers, called cytokines and chemokines, to induce inflammation that destroys organs," explains Dr. Nathan Karin of the Technion's Department of Immunology and the research team leader. "These proteins also attract white blood cells that, in the case of arthritis, attack joint tissues, and in the case of MS, attack brain components. Our method helps the immune system itself interfere with this process."
In untreated arthritis, part of the immune system detects one of the chemical markers, called IP-10, recognizes that it is wrongly labeling the body's own cells for attack, and destroys it. But while these naturally produced antibodies can slow, they cannot stop the progression of these diseases. In effect, there is a "civil war" within the immune system itself, with one part attacking and the other part protecting the body's own cells. The new approach seeks to help the "good" part of the immune system in its fight with the "bad" or autoimmune part.
The researchers first identified that IP-10 is one of the specific proteins responsible for the progression of these diseases, and more importantly that the immune system tries to restrain the harmful activity of IP-10 by producing auto-antibodies against it. They then generated a special vaccine that amplifies the production of these beneficial antibodies. This vaccine rapidly suppressed experimentally induced rheumatoid arthritis and MS.
Dr. Karin hopes that for rheumatoid arthritis this approach will replace older treatments, which are extremely expensive and require many repeated immunizations, and that it will also open new horizons for the therapy of MS.
"We are hopeful that the gene-based vaccine will be much better, since only a few vaccinations are needed to train the immune system to destroy IP-10, and the rat results indicate that chronic relief may be possible," says Karin.
While the vaccine will interfere with IP-10 when the immune system uses it to label actual invaders such as bacteria, Karin does not expect this will cause serious side effects.
"There are some 50 chemicals that the immune system uses to label cells to be attacked," he points out. "Knocking out one will not seriously weaken the immune system's response to infection or cancer. But in autoimmune diseases, where one part of the immune system is fighting another, eliminating IP-10 will shift the balance, giving the edge to the part that is protecting the body."
The next step is to move towards clinical tests of the vaccine in humans.
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