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 Information on oral tolerance and how to reverse diseases

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'Hair of Dog' Tried as Cure For Autoimmune Disease part-1

by Jane Broady

USING a technique reminiscent of the proverbial "hair of the dog," researchers have modernized an ancient Chinese remedy that shows great promise for treating and perhaps preventing various autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, insulin-dependent diabetes and uveitis, an inflammation of the eye that can cause blindness.

It may also one day make it possible to transplant organs between mismatched individuals by reducing or even eliminating the risk of rejection.

The treatment, called oral tolerization, seeks to turn off patients' rejection of their own tissue by feeding them small amounts of a protein directly or indirectly involved in the attack by their immune systems. The approach was derived from the well-established fact that people rarely mount an immune response to food.

For example, patients with diabetes would be given insulin, which is produced by the pancreas; those with multiple sclerosis already are being given a protein from the myelin sheath that surrounds nerves in the brain and spinal cord and patients with arthritis are being given the joint protein collagen. The first two are administered in powdered form, in a capsule, while the collagen is a liquid given in orange juice.

In early tests on human patients, oral tolerization has enabled some to stop taking steroids or other powerful immunosuppressant drugs with serious side effects; others have been able to greatly reduce their dependence on these medications, which indiscriminately interfere with the immune response. Instead of subjecting patients to an overall dampening of their immune systems with immunosuppressant drugs, induction of oral tolerance shuts down only one specific aspect of the immune response: the part that is causing disease.

Dr. Howard Weiner, an immunologist and specialist in multiple sclerosis at the Brigham and Women's Hospital and Harvard Medical School in Boston, calls oral tolerization "a form of vaccination via the gut."

"It stimulates the immune system in a way that helps the host suppress autoimmune disease," he said.

Perhaps most remarkable about the technique is its apparent safety. Dr. Weiner, a leader in the field, said, "There appear to be no side effects." This fact has prompted the Food and Drug Administration to sanction studies on people, some of which now involve hundreds of patients with autoimmune diseases.

Dr. Weiner said the technique is "so simple and apparently so safe that it seems too good to be true." In fact, nearly every scientist who is now working with it was skeptical at first and a few remain so, awaiting a clearer understanding of how oral tolerization works in test animals and in people.

However, when Dr. Lloyd Mayer, an immunologist at Mount Sinai Medical Center in New York, first suggested studying the technique, he said his Chinese-born graduate students told him: "This is old hat. The Chinese were doing this 4,000 years ago. If a patient had a problem with his pancreas, he was fed pancreas, and if a patient had a problem with his liver, he was fed liver." Dr. Mayer said that some people in the Chinese countryside still use this approach in an unscientific way, and Dr. Weiner said American Indians are also reported to have used it, eating poison ivy leaves to protect them against skin reactions to the plant.

Much of the research in oral tolerization is being supported by Autoimmune Inc., a Boston-based biotechnology company, as well as by the National Institutes of Health in Bethesda, Md. The American Autoimmune Related Diseases Association, Inc., a national organization based in Detroit estimates that 50 million Americans, mainly women, suffer from the more than 80 known autoimmune diseases.

Oral tolerization takes advantage of a very basic protective mechanism built into the body: the ability to prevent attacks on the various proteins, carbohydrates and microorganisms that are consumed in an ordinary diet. Dr. Mayer explained that the intestines house "the largest lymphoid organ in the body" and their job is to enable animals to ingest and digest food without the body launching an immunological attack against these "foreign" invaders. If these same foods were injected into the body, however, the part of the immune system that operates through the blood would marshall all its resources to eliminate them.

In laboratory animals with autoimmune diseases, feeding specific proteins has been shown to induce tolerance to the protein in question and also, apparently, to others nearby in the organ under attack. Dr. Weiner has dubbed this spread-out protection a "bystander effect." He explained that the protein that is fed may not necessarily be the one that the body attacks. Rather, in some cases it may simply serve as a means of directing the immune-suppressing cells to go to the diseased area, such as the myelin sheath or the insulin-producing cells of the pancreas.

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