Anti-Antibody Solution May Reduce Rejection After Transplant

A body's rejection of a donor heart is one of the most challenging barriers to a successful transplant. To address this challenge, the Heart Transplant Program at the Smidt Heart Institute is testing a new medication that could help patients whose bodies are likely to reject a donor organ.

Jignesh Patel, MD, PhD, medical director of the Heart Transplant Program, is leading a small pilot study to test a drug called eculizumab, which takes an unprecedented approach to thwarting the organ-rejection process

"We are the first and only medical center in the world to test this medication in this way for heart transplant patients," Patel said, "and we are very pleased with the outcome so far."

The human body maintains a finely tuned immune system that protects it from harmful invaders like toxins and dangerous bacteria. When a person receives a donor kidney, lung or heart, the immune system can recognize that organ as foreign and attack it.

‘We are the first and only medical center in the world to test this medication in this way for heart transplant patients, and we are very pleased with the outcome so far.’

Jignesh Patel, MD, PhD, medical director of the Cedars-Sinai Heart Transplant Program

Antibodies are among the body's most effective artillery in such an attack. The more antibodies a person's body has prior to a transplant, the more "sensitized" it is, increasing the chances of it destroying a new heart in a process called antibody-mediated rejection. About 20 percent of patients are so highly sensitized that they have great difficulty finding a suitable heart. Some cannot be matched with a donor at all.

Usually, when antibodies recognize a transplanted heart as foreign, they activate a pathway that will destroy the organ. The medication eculizumab works by blocking a component of that pathway.

"We are testing safety and looking at longer-term outcomes in 10 patients," Patel said. "After two years, nearly all of them are doing remarkably well with no evidence of their transplanted hearts working abnormally."

On the basis of these positive results, Patel is enrolling 10 more patients. The study is being conducted in partnership with the drug's manufacturer, Alexion.

Eculizumab (already on the market to treat a different condition under the brand name Soliris) has been tested in clinical trials for kidney transplants to great effect: it reduced antibody-mediated rejection from 41 percent to 8 percent.

The Cedars-Sinai study is timely, as more patients with greater antibody sensitization are in need of heart transplants. People build up sensitivity through various experiences, including pregnancy, blood transfusions and previous transplants. Young congenital heart patients are more likely to exhibit the condition, if they have had multiple surgeries and received donor valves or other tissues.

"More patients are living longer with more complex heart conditions," Patel said. "That's a positive thing, but it leads to some patients carrying a high antibody burden."

A number of therapies are available to reduce antibodies prior to a transplant, but results vary depending on the patient. Even when these approaches are successful, the patient can be left with residual antibodies, placing them at increased risk of rejection after transplant.

Patel is providing patients with eculizumab at the time of their transplant and following the surgery. He is trying to induce a phenomenon known as accommodation — if the body learns to live with a foreign organ for a little while, it may get used to it and accept it.

"We have yet to understand this mechanism," Patel said, "but patients who get this drug early on appear to experience a prolonged effect that allows the organ to survive."