"REBOOTING" - A Promise For Autoimmune Diseases?

Johns Hopkins University researchers have developed a new technique in treating autoimmune disease patients which reboots the immune system with results that have cured some patients while dramatically improving the health of others. This is a new approach to the use of stem cells in treating autoimmune disease.

Autoimmunity occurs when the blood's lymphocytes, which are designed to defend the body against infections and foreign agents, actually attack one or more of the body's organs. Researchers in the past have focused on ways to destroy the disease-causing lymphocytes and replace them with normal ones. That attempt has not been successful.

Bone marrow transplantation is now being used by many medical institutions worldwide. One attempt to get rid of the misdirected lymphocytes has been the use of high doses of cyclophosphamide, a chemotherapeutic drug. This method also calls for a blood stem cell transplant since it has been thought, incorrectly, that cyclophosphamide in high doses is destructive to the bone marrow's ability to make new blood cells.

Stem cells, present in both bone marrow and blood, regenerate marrow and blood after chemotherapy. In stem-cell transplants, stem cells are harvested before chemotherapy by drawing some of the patient's own blood or bone marrow. After the chemotherapy, the blood or marrow stem cells are returned to the patient's body.

However, patients who do go into remission after the procedure usually relapse after a time. This is thought to be the result of the "bad" lymphocytes returning to the patient along with the stem cells. How can pure stem cells be isolated from other blood cells? Now Johns Hopkins researchers have found a way to circumvent the problem.

According to Robert A. Brodsky, M.D., assistant professor in oncology and medicine at the Johns Hopkins University School of Medicine, "...stem cells contain an enzyme, called aldehyde dehydrogenase, which detoxifies cyclophosphamide. Like most blood cells, lymphocytes have very low levels of this enzyme, so cyclophosphamide destroys them but not the stem cells. That means it is not necessary to do a transplant to preserve the stem cells." He further states, "Studies have shown that after chemotherapy--as the stem cells turn into the specialized blood cells that have been destroyed--those that become lymphocytes are normal and do not attack the body. The immune system has been repaired."

This system was first tried with aplastic anemia patients. Seven out of the first ten patients treated by this method have remained disease-free for 10 years--and, in some cases, more than 20 years. The system was later tried with 27 other patients with autoimmune diseases, the majority of whom were lupus patients. Dr. Brodsky reports, "Most are still in remission, and some are off medications two and three years later." He continues, "All the patients we've studied have, at the very worst, remained stable: Virtually all have had major reductions in their immunosuppression medications." Dr. Brodsky cautions that, before this can be called a cure, the patients must remain disease-free for ten or more years.

Dr. Brodsky offers the comment that "When we have more information about the long-term effects of this treatment, and as more physicians and patients learn about it, the technique could well become standard protocol for autoimmune conditions soon after they are diagnosed and well before the diseases progress or become debilitating." (Watch for more on theimmune system in upcoming issues.)

Excerpted from Johns Hopkins "Health Insider," interview with Robert A. Brodsky, M.D., Johns Hopkins University School of Medicine (AMPS: East Central Florida Chapter 5/2000)