Drug could ease side effects for transplant patients

University researchers have taken a big step toward freeing transplant patients from the powerful, and sometimes harmful, drugs they now take to keep their bodies from rejecting new organs.

At the Fifth International Conference on New Trends in Immunosuppression, UW researcher and transplant surgeon Stuart Knechtle presented findings of a 24-patient pilot study approved by the U.S. Food and Drug Administration last August. The findings showed 23 patients went off dialysis after transplant, with all but four patients using only one daily anti-rejection drug, rapamycin.

“For years, patients have taken various drugs following transplantation, with the hope that rejection would not occur,” says Knechtle, an expert on immune-suppression research and professor of surgery at UW Medical School. “This study is a significant step forward, in that it will vastly improve the quality of life for transplant patients if these initial results last for many years.”

Transplant recipients who receive new organs typically take a steroid, such as prednisone, and other drugs for the rest of their lives to prevent rejection. Though the drugs are effective in keeping the immune system from attacking the new organ, they also can cause serious complications, such as heart disease, kidney failure and diabetes.

Knechtle and colleagues were the first to show in 1996 that eliminating immunosuppressive drugs worked in primates. In the results presented in Geneva, Knechtle and colleagues tell how 24 kidney transplant patients used an antibody called Campath-1H, a substance that attaches to specific cell types that attack and destroy what they perceive as foreign to the body.

So far, participants have received two doses of Campath-1H, one on the day of transplant and another a day later. In combination with Campath-1H, patients were administered a low dose of Rapamycin, a standard anti-rejection drug.

“Of 24 patients, 23 have good kidney function, and four have shown some signs of rejection which has been treated,” says Knechtle. All patients are at home and doing well, adds Knechtle.

“Until now, we have never been able to completely discontinue or reduce immunosuppressive drugs without causing organ rejection. These results are extremely valuable for transplantation and could change the standard of care in the future,” he says.

In recent months, Knechtle and colleagues have received additional funding from the National Institutes of Health and the Immune Tolerance Network to increase the number of study participants to 60, as well as to further investigate the keys to immune tolerance.

The UW transplant program, one of the largest in the country, performed more than 500 organ transplants last year. It has long been a pioneer in organ transplantation, such as developing an organ preservative solution that widely used today. It also is a national leader in obtaining organ donations.