Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham health system, officially opened the Legorreta Center for Clinical Transplant Tolerance, the first-of-its kind center in the world dedicated to preventing organ rejection after transplant surgery without the use of lifelong immunosuppressive medications. Immunosuppressive medications prevent the immune system from rejecting a transplanted organ, but come with serious side effects, increasing the chance of infections and other illnesses like cancer, diabetes, and heart disease. The mission of the Legorreta Center is to eliminate these risks by eliminating the need for lifelong immunosuppression, improving both the quality-of-life following organ transplantation while extending patient survival.
Newly transplanted organs are considered foreign by the recipient's immune system, so the immune system attempts to reject them. The new Center's team will aim to prevent this from happening using a protocol, developed at MGH, which conditions the immune system into ignoring the transplanted organ, a process called immune tolerance. Bone marrow or blood stem cells from a kidney donor are given to the kidney recipient contemporaneously with the transplant surgery. In the weeks after the recipient's bone marrow infusion, the donor cells train the immune system of the recipient to recognize the new organ as not foreign. While immunosuppressants are still required immediately following surgery at lower doses than conventional transplants, this protocol allows patients to eventually be gradually weaned off their immunosuppressants over a six to twelve month period.
Tatsuo Kawai, MD, PhD, an MGH kidney transplant surgeon for more than 20 years and a leading transplant tolerance expert, will serve as the Center's first director.
Over the last almost four decades, our transplant patients have been treated with the same three powerful but toxic immunosuppressive medicines with no major advances in the field. However, we are now ready to radically change the care of transplant patients through transplant tolerance."
Dr. Tatsuo Kawai, MD, PhD, an MGH kidney transplant surgeon
The Legorreta Center was established with a generous $25 million donation by Pablo G. and Almudena Legorreta. Pablo Legorreta is the founder and Chief Executive Officer of Royalty Pharma, the world's largest acquirer of biopharmaceutical royalty streams and a leading funder of innovation across the life sciences ecosystem. The donated funds will be used to support clinical trials in the emerging field of transplant tolerance. The gift also establishes the Legorreta Endowed Fund for the Center for Clinical Transplant Tolerance, part of which will be used to encourage basic and translational laboratory studies by young investigators.
"My wife, Almudena, our family and I are grateful for the groundbreaking clinical achievements made by MGH and its team that have enabled transplant patients to thrive without the need for lifelong immunosuppressants," said Pablo Legorreta. "Our family has been a beneficiary of this life-changing approach developed by MGH physicians, through their cutting-edge research performed for more than 40 years. It is a privilege for our family to support the creation of the Center for Clinical Transplant Tolerance at MGH, to support continued translational research in transplant tolerance, as well as ongoing clinical trials and better treatment of transplant patients.
Kidney transplants account for most organ transplants across the United States and are the most common transplant surgery performed. As such, only kidney recipients are presently eligible to be Center patients, but MGH researchers are working on expanding tolerance induction to all organ transplant patients. MGH is currently enrolling patients in FDA-approved clinical trials for prospective living donor and deceased donor recipients as well as previous living donor kidney recipients if their donor is available to provide bone marrow or blood stem cells.
"Dr. Kawai has devoted his career to the goal of bringing the promise of transplant tolerance to his patients. After decades-long preclinical and clinical research, he is now poised to do just that with the opening of the Legorreta Center," said Joren C. Madsen, MD, DPhil, Director, MGH Transplant Center.
MGH has been a leader in transplant tolerance for more than four decades, pioneering the tolerance protocol described above in 1998 when patient Janet McCourt of Quincy, Mass., who was suffering from myeloma and kidney failure, received an HLA-matched combined kidney and bone marrow transplant from her sister. Former MGH transplant immunologists David Sachs, MD, Megan Sykes, MD, and hematologist Thomas Spitzer, MD devised the protocol, while A. Benedict Cosimi, MD, and Dr. Kawai performed the operation. Ms. McCourt, now in her 80s, has lived free from myeloma and without immunosuppressants for 25 years. This study was then extended to HLA mismatched kidney transplant recipients without malignancies, solely to induce transplant tolerance by Drs. Kawai, Cosimi and Sachs in 2002. Since then, immunosuppressive drug-free transplant kidney survival up to 17 years has been achieved in the MGH clinical trials.
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