Outsmarting the immune system:

Dr. Camille Hancock Friesen seeks to prevent rejection of transplanted hearts

While heart transplants save lives, they come with life-threatening risks. To keep a patient’s immune system from rejecting the donor heart, drugs are used to shut down the recipients’ immune response. “These drugs are especially hard on children and greatly increase their lifetime risk of cancer and serious infections,” says Dr. Camille Hancock Friesen, a cardiac surgeon who works with children and adults. “We need a more selective way to suppress the immune response to donor hearts… so the heart is protected and so is the rest of the body.”

Dr. Hancock Friesen wants to trick the immune system into accepting the donor heart – before the transplant operation even takes place. Her strategy, called ‘tolerance induction,’ is like vaccination in reverse. “Vaccination triggers the immune system to recognize and destroy foreign proteins, while tolerance induction conditions the immune system to accept foreign proteins,” explains Dr. Hancock Friesen, assistant professor in Dalhousie Medical School’s Division of Cardiac Surgery and a member of the Cardiovascular Research Group.

In laboratory studies, Dr. Hancock Friesen’s associates here have already proven that tolerance induction works – for kidneys. But the heart’s blood-pumping role makes it particularly vulnerable to ischemic damage, which is cell death caused by lack of oxygen. “You can’t avoid ischemic damage with a transplanted heart,” she says, “but we’ve found it makes the heart more prone to immediate rejection than other organs.”

To overcome this challenge, Dr. Hancock Friesen is identifying target proteins. “We want to use these proteins to induce specific tolerance to the kinds of proteins found in donor hearts,” she says. “Given before surgery, these proteins could condition the patient’s immune system to accept the donor heart, and reduce or eliminate the need for immunosuppressive drugs. This would be a huge advance for transplantation.”

Even with immunosuppression therapy, 50 per cent of transplanted hearts fail within 10 years, due to the subtle, ongoing immune response known as chronic rejection. Pre-conditioning the body to accept the donor heart may provide patients with many long healthy years.