Posts Tagged ‘transplant rejection’

Emory Receives $20 Million Grant from NIH for Continued Transplant Research

Emory Transplant CenterIn the last few years, thanks to the development of anti-rejection drug therapies, outstanding breakthroughs in short-term outcomes have been achieved among organ transplant patients. We first introduced you to belatacept on our blog in September of 2010, while the medication was being studied by our team of doctors and researchers. Then in June of last year, we announced the FDA’s approval of belatacept and its confirmed ability to provide a less toxic alternative to the standard anti-rejection medications, including calcineurin inhibitors like cyclosporine.

Even with these developments, though, significant challenges remain for patients over the long term with organ rejection and drug toxicity that often leads to cardiovascular disease, infection or cancer.
To help overcome these challenges, a new $20 million grant has been bestowed upon Emory from the National Institute of Health to allow physician/researchers to develop better treatments for organ transplant recipients that help avoid both organ rejection and drug toxicity. The new grant builds upon more than 18 years of groundbreaking research by Emory scientists—such as the investigation into belatacept—that has already significantly advanced the transplant field.

Christian Larsen, Emory Transplant Center Director

Dr. Larsen

“Despite tremendous advances in immune drug therapy, the fact remains that organ recipients still must take immunosuppressant drugs over their lifetimes,” says Chris Larsen, MD, PhD, executive director of the Emory Transplant Center and principal investigator of the new grant. “Improvement in these transplant drugs is still a critical need for avoiding acute and late-stage rejection. Ultimately, we want to improve overall health while reducing cost through improved outcomes with fewer drugs.”

In addition to Dr. Larsen, project leaders from the Emory Transplant Center will include Allan D. Kirk, MD, PhD, scientific director of the Emory Transplant Center and a Georgia Research Alliance Eminent Scholar; Leslie Kean, MD, PhD, Emory associate professor of pediatrics and director of the Pediatric Bone Marrow Transplant Division of the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, Stuart J. Knechtle, MD, surgical director of the liver transplant program at Emory Transplant Center and Children’s Healthcare of Atlanta, and Andrew Adams, MD, PhD, assistant professor of surgery.

“The most important feature of this award is its support for multiple investigators attacking the problems of immunosuppression from different but complementary angles,” says Kirk. “The team science approach is the best way to get results to our patients.”

Several projects funded by the new grant will aim to develop more effective transplant drugs and strategies to avoid immunosuppressant drugs altogether.

An additional project will develop strategies to overcome immune sensitization in patients who have had previous transplants, pregnancies or blood transfusions. These patients often are not candidates for transplant because of their increased risk of rejection.

For more information about the Emory Transplant Center, its research projects and clinical programs please  use the Related Resources links below.

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A Life Free From Anti-Rejection Medication Post-Transplant?

A life free from taking anti-rejection medications post-transplant…is it possible? After transplant, patients must take multiple medications to keep their bodies from rejecting the new organ. The side effects of these immunosuppressant drugs, for many, can be grueling. Side effects range from fatigue to high blood pressure to increased risk of infection. Researchers are currently evaluating whether it’s possible for kidney transplant patients to avoid use of immunosuppressant drugs post transplant. They’ve found that it’s possible that by not only transplanting the living donor organ but also some of the donor’s immune producing cells, it  may be possible to deceive the recipient’s immune system into accepting the new organ as its own.

To evaluate the likelihood of decreased reliance on immunosuppressant drugs for kidney transplant patients, researchers collect immune system-producing stem cells and other immunity cells from the living donor’s bloodstream. They infuse transplant patients with radiation and medications to wipe out part of their own bone marrow.  This allows the donated cells to squeeze in and create a sort of ‘mixed’ immunity that prevents rejection.  In essence, a kidney transplant patient would also be receiving a bone marrow transplant.

Dr. Kenneth Newell

Dr. Kenneth Newell

At the Emory Transplant Center, researcher Dr. Kenneth Newell, is compiling a registry of kidney recipients who somehow survive despite quitting the pills on their own because they couldn’t afford them or because of side effects – a truly rare case.  Thus far, Dr. Newell has discovered about three dozen of these cases.  The research team at Emory is testing these patients for biological markers that might explain why they fared well and who else is a good candidate.  This may provide clues that a completely separate part of the immune system plays a role in organ rejection/acceptance.

In the meantime, the Food and Drug Administration (FDA) approved the drug belatacept (Nulojix®) for the prevention of graft rejection after kidney transplants.  This is the first time a new class of drugs has been developed for transplant since the 1990s.  Belatacept has the potential to improve and simplify the medication regimens of kidney transplant recipients, being a less toxic alternative to calcineurin inhibitors, with fewer side effects such as high blood pressure, high cholesterol, kidney toxicity and diabetes.  It is now being offered at the Emory Transplant Center, where Emory physicians played a role in discovering this new drug.

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Emory Researchers Investigate Methods for Reducing Transplant Rejection

Transplant Center OutcomesOrgan transplant rejection is a fear for many people faced with a possible need for transplantation. For this group of transplant candidates, some good news has come from recent research taking place at the Emory Transplant Center. Emory’s research shows that a new immunosuppressant protocol could convince a transplant recipient’s immune cells to switch sides by converting cells that normally recognize and attack transplanted organs to cells that control the immune response instead—and protect the grafted organ. This may give patients a better chance of avoiding rejection of the transplanted organ and help them wean off anti-rejection drugs over time, reducing the rate of long-term complications after transplant.

Dr. Mandy Ford

Mandy Ford, PhD

Emory’s Dr. Mandy Ford, assistant professor of surgery, is the senior author on the study, published this month in the Proceedings of the National Academy of Sciences Early Edition. The National Institute of Allergy and Infectious Diseases funded the study.

Emory transplant researchers found that an experimental combination of treatments can induce turncoat behavior among immune cells in mice with skin grafts. The combination included a transfusion of spleen cells from the donor, as well as a limited course of a drug that blocked immune cell signals from the CD154 molecule. The grafts survived for months. If one part of the combination was deleted, then the grafts didn’t last more than a few weeks.

“Using this treatment protocol, we found that a subset of cells that would normally attack the graft instead turn on a gene that instructs them to become graft-protective,” Dr. Ford says. “These protective cells, called regulatory T cells, are present in everyone’s immune system and normally prevent us from developing autoimmunity.”

Unfortunately, using drugs that block CD154 clinically in humans has the drawback of causing blood clots. But Dr. Ford says that Emory researchers are investigating the possibility of blocking CD154 signals in a different way to avoid the blood clotting mechanism, such as using donor-specific transfusions to control the immune system. The Emory Transplant Center is currently studying donor-specific transfusion (but with different drugs, not anti-CD154 drugs) as part of an experimental kidney transplant protocol.

We’ll keep you updated on this innovative transplant research. If you have questions on this research for our team, or thoughts you’d like to contribute, please feel free to use the comments section below!

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