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Post-transplant combo can replace toxic immune-suppressing drugs in monkeys
Date:7/8/2009

Transplant patients rely on drugs to prevent graft rejection, but at the cost of serious side effects. The class of immunosuppressive drugs known as calcineurin inhibitors (examples are cyclosporine and tacrolimus) can damage patients' kidneys and lead to high blood pressure, among other problems.

A combination of treatments can effectively replace calcineurin inhibitors in preventing graft rejection when kidney transplants are performed on monkeys, scientists at the Emory Transplant Center have shown. The non-human primate research was conducted at the National Institutes of Health and Yerkes National Primate Research Center, Emory University.

The results are published in the July issue of Nature Medicine.

The finding opens the door to less-toxic post-transplant treatment that could be administered once a week rather than a dizzying mound of pills every day, says senior author Allan Kirk, MD, PhD, scientific director of the Emory Transplant Center and a Georgia Research Alliance Eminent Scholar.

"Both of the drugs used in this regimen are already used separately in humans, thus a clinical trial could be developed quickly," Kirk notes.

One key ingredient in the combination is an experimental therapy called a costimulation blocker, designed to interfere with the T cells that cause graft rejection without affecting other organs. Costimulation refers to one of two signals T cells need from other cells (antigen presenting cells) to become fully activated.

The other key ingredient -- a protein called alefacept -- subdues memory T cells, a variety of T cells that allow the immune system to respond faster and stronger to an infectious agent or vaccine upon second exposure.

Costimulation blockers are sufficient for allowing mice to tolerate a transplanted kidney, but not monkeys or people, Kirk says. Memory cells appear to prevent costimulation blockers from working as well in monkeys as they do in m
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

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