A study conducted in rats has given researchers hope that gene therapy may some day be used to prevent chronic organ rejection.
In the study, Si M. Pham, MD, and colleagues at the University of Pittsburgh Medical Center found that transplant arteriosclerosis was prevented with inducible nitric oxide synthase (iNOS) in rats receiving aortic grafts.
The investigators performed aortic transplants between genetically unrelated rats. Twenty-eight days following transplantation, the aortic grafts that had not been treated with the iNOS gene prior to transplantation showed severe arteriosclerosis. In contrast, grafts that received the iNOS gene had no signs of arteriosclerosis.
The researchers developed the iNOS gene therapy strategy after discovering that cyclosporine inhibits the natural production of iNOS in rats and that inhibiting the production of natural iNOS can accelerate chronic rejection, as evidenced by arteriosclerosis.
"Our study suggests that iNOS expression partially protects aortic transplants from the development of arteriosclerosis and that iNOS gene transfer strategies may prove useful in preventing the development of this otherwise untreatable disease process," said Dr. Pham. In addition, "gene therapy may allow iNOS expression to continue even in the face of high levels of cyclosporine and steroids," he said.
The findings were published in October in the Journal of Clinical Investigation (1997;100:2035-2042).
For Your Information:
Si M. Pham, MD
Suite C700, Presbyterian University Hospital, 200 Lothrop Street, Pittsburgh, PA 15213
412-648-9758 (phone); 412-648-1029 (fax)
pham@pittsurg.nb.upmc.edu
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