PREVENTING TRANSPLANT REJECTION
Organ transplant recipients not only get an organ, but also a second chance at life. But with that new organ comes a completely new set of problems. One doctor is hoping to make organ rejection a thing of the past.
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More than six years ago, Melinda hair's heart started to fail. She had a condition called cardiomyopathy.
Melinda Hair
Had heart transplant
"There was a picture taken of me that I looked a little faded and I felt like that's what was going on. That I was just fading away."
Melinda needed a new heart. After just one week on a waiting list, she got one.
Melinda Hair
"I had a chance of a new healthy life, and yet, I knew that there's always a chance, when you go into any type of surgery, that you might have complications."
Up to 60 percent of organ recipients will reject their new organ. That rejection can range from minor to life-threatening.
Dominic Borie, M.D., Ph.D.
Organ Transplant Surgeon
Stanford University
Stanford, CA
"What we need to find now is solutions that will make sure that once the organ is implanted, it will stay implanted and functioning forever."
Transplant surgeon Dominic Borie is studying this new compound in animals to reduce the risk of rejection. It targets and destroys cells that would reject the organ.
Dominic Borie, M.D., Ph.D.
"If we have a drug that would be efficient and wouldn't create any side effects, then that's as good as it gets."
Doctor Borie says the exciting part is that this compound does not increase the risk of cancer, heart disease and diabetes, like current drugs do.
After recovering from one life-threatening rejection incident already, Melinda is grateful for the research. But for now, she's staying focused on just one thing.
Melinda Hair
"To just not to forget to enjoy life and to cherish it every day."
Human studies of the drug are planned, which Doctor Borie says could change the future of organ transplantation. He says if it's successful, this compound could also be used to help a variety of autoimmune diseases -- not just organ transplants.
BACKGROUND: According to the United Network for Organ Sharing, 83,888 total candidates are listed on the national organ transplant waiting list as of April 2004. During 2003, there were 25,451 transplants performed in the United States. A transplant offers a second chance at life for most recipients, but with that new organ comes a new set of problems: transplant rejection.
Transplant rejection is when a transplant recipient's immune system attacks a transplanted organ or tissue. The body's immune system protects against potentially harmful substances, such as microorganisms, toxins, and cancer cells. These harmful substances have proteins called antigens on their surfaces. If the immune system identifies antigens that are not part of the body, it will attack the substance. Though tissue typing ensures that the organ or tissue is as similar as possible to the tissues of the recipient, the match is usually not perfect. No two people (except identical twins) have identical tissue antigens. Because of this, immunosuppressive drugs are needed to prevent organ rejection. Otherwise, organ and tissue transplantation would almost always cause an immune response and result in destruction of the foreign tissue.
IMMUNOSUPPRESSIVE RISKS: Dominc Borie, M.D., Ph.D., from Stanford University, says rejecting organs is of major concern to physicians and patients. Since the advent of immunosuppressive drugs to help prevent rejection in organ transplant recipients, he says the success rate of transplantation has skyrocketed. However, he says, "The [immunosuppressive drugs that are used to prevent rejection] are very powerful. There is a price to pay … these drugs have so-called side effects … and these side effects are an area of concern because many of them … will significantly increase the cardiovascular risk in organ transplant procedures and then ultimately may effect the odds of survival. That's one of the big problems right now." Developing cancer or diabetes from suppressing the immune system are also risks that come with transplantation.
NEW COMPOUND: Dr. Borie is currently studying a new compound (currently called CP-690,550) that could suppress the immune system and prevent the rejection of a transplanted organ without major side effects. The drug specifically targets immune cells that cause rejection. In animal studies, the drug caused only minimal side effects. Current therapies affect a variety of cell types, leading to side effects that include a weakened ability to fight off infection; an increased rate of cancer, diabetes and high blood pressure and cholesterol; and damage to the nervous system and kidneys. The ideal immunosuppressant would block the actions of the immune cells that cause organ rejection without interfering with other cells. CP-690,550 appears to be on that track.
"Theoretically, the molecule that we are targeting with the drug is present only on immune cells, not throughout the body," says Dr. Borie. "We have shown that targeting a pathway that is specific to immune cells provides efficacy. And on the basis of the data we have now, we feel that very likely the side effects of the drug in humans will be limited." At the low effective doses, researchers saw no evidence of metabolic abnormalities, such as problems with glucose or lipid levels, and no increased rate of cancer or infections.
The drug also shows promise as a therapy for quieting the overactive immune system in patients with autoimmune diseases.
American Organ Transplant Association
www.a-o-t-a.org/
Copyright © 2004 Ivanhoe Broadcast News, Inc.
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