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Cancer drug shows promise against graft vs. host disease
Date:7/10/2008

ANN ARBOR, Mich. A new University of Michigan study in mice suggests that a drug recently approved to fight cancer tumors is also able to reduce the effects of graft-versus-host disease, a common and sometimes fatal complication for people who have had bone marrow transplants.

Plans are under way at U-M for an initial trial of the drug in people as a new way to prevent graft-versus-host disease. Researchers expect to begin a trial within a year.

The U-M scientists tested the effects of the drug SAHA, as well as another member of a group of drugs known as HDAC inhibitors, on key immune system cells called dendritic cells. In mice, both drugs were able to significantly diminish the destructive inflammatory effects that these cells cause in graft-versus-host disease.

Graft-versus-host disease occurs when immune cells in the transplanted bone marrow mount a misguided attack on body tissues. If HDAC inhibitors turn out to be safe and effective in people, they might offer a treatment option preferable to the immunosuppressant drugs used now to treat the disease. These leave people vulnerable to infection and have other significant side effects.

"To make bone marrow transplants more effective, we need better control of the very powerful reactions between the immune systems of the donor and recipient. This study shows how drugs like SAHA regulate those reactions, and takes us a major step closer to bringing this new approach to patients who need transplants," says James L.M. Ferrara, M.D., director of the U-M Combined Bone Marrow Transplant Program and a senior author on the study. Ferrara is also professor of internal medicine and pediatric and communicable diseases at U-M.

"These HDAC inhibitors were thought to just kill cancer cells, but at lower doses, it's possible they can modulate a number of immune diseases," says Pavan Reddy, M.D., the study's lead and corresponding author, and an assistant professor of in
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Contact: Anne Rueter
arueter@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert  

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