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BWH remains poised at the forefront of transplant research today, 50 years after Dr. Joseph Murray’s historic kidney transplantation.
Carrying on the tradition is Mohamed H. Sayegh, MD, director of the recently established joint Transplant Research Center with Children’s Hospital Boston. Sayegh is the principal investigator of a new $13.5 million NIH grant awarded to form a consortium of transplant centers that will develop novel strategies for improving the long-term success of organ transplantation. Other members of the consortium include Massachusetts General Hospital, Beth Israel Deaconess Medical Center, and University of California at San Francisco. The strategies will be tested in kidney and heart transplant recipients. Immunosuppressants, first used by Murray and others in the 1960s, allowed transplantation to become widespread by suppressing the patient’s immune system to allow a donor organ to function. But at the same time, they caused serious side effects including diabetes, skin cancer, high blood pressure, hair growth, tremors, osteoporosis, and increased susceptibility to infections. And the drugs must be taken for life. Over the years since the early successful transplants, a persistent problem emerged – that of chronic rejection. Some four to five percent of transplanted kidneys are lost in the first year, and approximately 50 percent are lost at the 10-year mark. “The goal of our research is to reduce chronic rejection by providing optimal immunosuppression yet minimizing the use of toxic drugs that contribute to long-term dysfunction,” says Sayegh. “We can prevent and even reverse early (acute) rejection, but dealing with chronic rejection has been more elusive.” In 2002, BWH identified the response of lymphocytes (a type of white blood cell) to donor antigens in an in vitro assay as an indicator of high and low risk for development of chronic rejection. Inhibiting this response and preventing chronic rejection may also help address organ shortages, as fewer transplant recipients require multiple transplantations.
“The good news is, our research is bringing us closer to gentle, yet effective, immunosuppression that will improve long-term success of organ transplantation. Our vision is for a new generation of immunosuppressive drugs that will enable patients to enjoy a higher quality of life and avoid the complications too often associated with transplantation,” said Sayegh.