Researchers heal hearts dealing with rejection

The mending of broken hearts is emerging as a possibility as new scientific breakthroughs hit center stage.

The majority of heart transplant research is focused on improving the conditions of living with a new heart by rewiring and changing the immune system in such a way as to make it more welcoming to the new organ.

“By manipulating the immune system at the time of transplant, one can trick the body into accepting the new heart,” said Dr. Daniel Marelli, a cardiac surgeon in the UCLA Heart Transplant Program.

A new strategy that has been used to approach immune response has included adopting termed tolerance, an older concept of immunization, and applying it to the science of heart acceptance and rejection.

By doing so, researchers have entered into a new realm of possibilities for finding cures ““ instead of just treatments ““ for heart ailments, said Dr. Jon Kobashigawa, clinical director of the UCLA Heart Transplant Program.

Kobashigawa said that the concept of tolerance, preparing a recipient’s body for a foreign organ in small, incremental doses to avoid transplant rejection, has been around for many years.

“It is essentially the switching of immune systems,” Kobashigawa said. “However, we are still evolving in terms of understanding the mechanisms of rejection and tolerance.”

Since rejection of a new heart is the primary cause of death during the first year after a transplant, work is being done to create better and stronger immune-suppression drugs. Until a long term anti-rejection strategy is found, the drugs will have to serve as bandages to buy researchers time.

In recent years, newer and more effective immune-suppression drugs have provided assistance to many transplant patients and improved their quality of life, Kobashigawa added.

With better anti-rejection medications becoming available, patients can avoid some of the symptoms, ranging from diabetes to hypertension, that go along with a weak immune system.

But finding a way to avoid these drugs altogether is the ultimate research goal and tolerance may hold the key, Kobashigawa said.

The New England Journal of Medicine published research on the ability to induce immune tolerance after kidney transplants, allowing patients to stop taking anti-rejection drugs up to five years after the surgery.

To weaken and prepare each patient’s immune response, recipients were injected with bone marrow from the donor, forming a new immune system that would accept the organ as its own.

The success of the study sheds light on the possibility of extending life after transplantation, as well as improving the quality of life, by creating a situation where the new heart is fully accepted by the body, Kobashigawa said about the study.

Even though the study is a breakthrough, it has not solved the dilemma of reduced life expectancy caused by organ transplantation, he added.

Future research aims to use more natural routes to achieve tolerance by tinkering with white regulatory cells. Those cells shut down the immune response and, if kept under control, can be activated to suppress the attack response, he added.

In addition, newer methods, such as gene therapy, are in the forefront of exploration for researchers, Kobashigawa said. Gene therapy is a process of injecting genetic codes into cells of the donor organ so that they no longer are able to express foreign antigens, so that the organ will not be attacked when placed in the recipient. In such situations, drugs are not necessary to maintain a state of equilibrium.

Research that can be applied to the clinical world is of growing importance now, said Dr. Juan Alejos, director of the Pediatric Heart Transplant Program at UCLA. Patients who were given successful heart transplants 10 years ago are reaching a point where they will need extra treatment to keep their hearts functioning properly.

“The new heart does not last forever, but we can try and improve upon the length,” Alejos said. “Our own success has created newer problems that need to be dealt with.”

Doctors hope that mastering therapy with the use of tolerance will allow transplanted hearts to last as long as 20 to 30 years, providing the key to increased life post-transplant.

The current numbers show that seven years after a heart transplant, 90 percent of patients have a high quality of life and work half- or full-time, Marelli said. About 30 years ago, these numbers were much lower on average, with a 5-year survival rate and lower life quality after operation, he added.

Though the field of giving new life to hearts continues to advance, much of the research is still years away from clinical application, Marelli said. UCLA performs more than 100 transplants each year.

“The part of the operation that tickles the imagination most is in taking a human heart that is in constant motion outside the body in an arrested state, storing it for 4 hours, and placing it into another person,” he said. “By giving the heart warm blood, it begins to beat again and resumes automaticity within the new body.”

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