Preventing Organ Rejection: Could Cows Hold the Clue?

MADISON - Every week, Dr. Hans Sollinger hops on his bicycle and pedals out to the fields, farms and back roads of northeastern Madison as part of his exercise routine.

But little did the surgeon who heads the transplant program at UW Hospital and Clinics realize that he's been biking right past the source of a scientific discovery that could prevent the most common cause of organ rejection in kidney transplant patients: Milk from genetically engineered cows.

Each year, thousands of kidney transplants fail because of antibody-mediated rejection (AMR), a phenomenon in which a patient's immune system triggers the production of antibodies that activate a protein call human C1. The protein attacks the tissue of a transplanted kidney, a process that often leads to the body rejecting the organ. In the United States, more than 15,000 kidneys are transplanted each year, and UW Hospital and Clinics transplants more than any other program.

The key to stopping AMR may lie in the milk of the cows that live on a biotech farm in northeastern Madison – milk teeming with recombinant C1 inhibitor.

Sollinger recently received approval from the University of Wisconsin School of Medicine and Public Health's Institutional Review Board to begin work on a clinical trial that will test whether elevating the levels of C1 inhibitor in transplant patient can disrupt the chain reaction that cause AMR. Surgeons will identify patients who are experiencing AMR following a kidney transplant. Half of the trial group will receive the current standard treatment – a blood-cleansing procedure called plasmapheresis plus steroids – while the other half will receive a dose of recombinant C1 inhibitor.

"A transplant typically rejects one of two ways - either by immune cells or by antibodies," explains Sollinger. "We can combat the immune cell reaction with cyclosporine and other immunosuppressant agents. Where we are not good is combating antibodies. There's nothing we can do except for washing the antibodies out of the blood, but it's a very time-consuming and expensive process, and most of the time the effects are very short-lasting."

Sollinger's hopes for success are bolstered by medical precedent. Boosting the levels of human C1 inhibitor already works to combat a rare disease called hereditary angioneurogenic edema, a condition in which antibodies trigger swelling and lesions of the skin and mucous membranes.

The trial builds on the work of Dr. Paul Terasaki, the famous transplant surgeon who championed the theory that antibodies, not immune cells, hold the key to preventing organ rejection.

"Dr. Terasaki showed us that in the long term, the grafts that are failing are failing because of antibodies," says Sollinger. "They're a huge problem, and now, for the first time, we have an agent to address it."

The trial is sponsored by and will be conducted in conjunction with Pharming, a European-based biotech company. Sollinger hopes to have results in as little as a year.

"That's why this trial is so exciting," he says. "This is not one of these drugs where we'll have to wait for years to see if it works. We'll know right away."

The transplant program at UW Hospital and Clinics is one of the world's foremost transplant programs, encompassing heart, lung, kidney, pancreas, intestine, islet cell and pediatric transplants. UW Health surgeons are physicians are recognized as experts and pioneers in new surgical techniques.