Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer drug shows promise for treating graft-versus-host disease

11.07.2008
HDAC inhibitors may provide novel way to treat major complication of bone marrow transplants, as well as autoimmune diseases

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 internal medicine at the U-M Medical School. "The mechanism we have identified in graft-versus-host disease may be involved in autoimmune diseases as well."

The study appears in the July issue of the Journal of Clinical Investigation.

Context:
Bone marrow stem cell transplants are most commonly used to treat leukemia and lymphoma. By replenishing depleted blood cells, the transplants allow higher doses of chemotherapy to more effectively get rid of cancer cells.

But as many as half of bone marrow transplant recipients develop acute or chronic symptoms of graft-versus-host disease, which can affect the skin, liver and gastrointestinal tract. Reddy calls the disease "the single biggest barrier to bone marrow transplant."

The study suggests a novel way to treat graft-versus-host disease with an already available drug that is stirring considerable interest as an anti-cancer agent. The FDA approved SAHA, marketed under the name Vorinostat, as a treatment for one kind of lymphoma in 2006 and for leukemia in 2007. SAHA is being used off label for other cancers, including lung, brain and colon cancer.

The U-M study adds to a growing body of research suggesting HDAC inhibitors also may be useful tools to reign in misguided immune responses. Researchers elsewhere have recently shown that HDAC inhibitors have been beneficial in animal studies of lupus and inflammatory bowel disease. Other studies suggest the drugs could be useful in regulating the immune response in heart and islet cell transplants.

Research details:
The U-M researchers studied the responses of immune system dendritic cells in mice given SAHA and ITF 2357, another new HDAC inhibitor. Dendritic cells are important immune system cells whose varied roles are beginning to be fully understood.

The scientists looked at the two HDAC inhibitors' effects on mouse and human dendritic cells in culture. They found that as they suspected, the drugs acted to diminish the dendritic cells' key role in promoting pro-inflammatory proteins called cytokines. Specifically, the researchers found that the HDAC inhibitors increase the expression of IDO, an enzyme which represses dendritic cell activity.

They tested the HDAC inhibitors in mice bred to display the effects of graft -versus-host disease. When they injected the mice with dendritic cells treated with the drugs, they found the drugs were able to reduce the disease's effects.

The clinical trial: The trial is not yet recruiting patients. For questions and information on the U-M bone marrow transplant program, contact the U-M Cancer AnswerLine, 800-865-1125, canceranswerline@med.umich.edu

Journal citation: Journal of Clinical Investigation, Vol. 118, no. 7, July 2008, www.jci.org

Funding: National Institutes of Health, Doris Duke Clinical Scientist Development Award, Amy Strelzer Manasevit-National Marrow Donor Program

Additional authors: Yaping Sun, M.D., Ph.D., Elizabeth Weisiger, B.S., Yoshinobu Maeda, M.D., Ph.D., Oleg Krijanovski, M.D., Ph.D., Chelsea Malter, B.S. and Tomorni Toubai, M.D., Ph.D., U-M Department of Internal Medicine; Raimon Duran Struuck, D.V.M., Shawn G. Clouthier, M.S., Isao Tawara, M.D., Ph.D. and Erin Gatza, Ph.D., Department of Pediatrics, U-M Comprehensive Cancer Center; Cen Liu, M.D., Ph.D., University of Florida; Paolo Mascagni, Ph.D., ItalFarmaco S.p.A., Milan, Italy; and Charles A. Dinarello, M.D., University of Colorado Health Sciences Center.

Anne Rueter | University of Michigan
Further information:
http://www.jci.org

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>