U.S. Agency for Emergency Preparedness Awards $10.4M Research Contract to University of Rochester

URMC Researchers to Investigate Medical Countermeasures to Radiation Exposure

December 15, 2008

The University of Rochester has received a $3.18 million first-year government contract, with an option to increase to $10.4 million over the next three years, to investigate a “post-radiation pill” in the event of an accident or act of terrorism with nuclear or radiological devices.

Rochester researchers, led by principal investigator Yuhchyau Chen, M.D., Ph.D., will test eltrombopag* for its ability to replenish blood platelets following injury from radiation. Because eltrombopag is available in tablet form, rather than as an injection, Chen hopes it will serve as a convenient therapy in a medical emergency involving hundreds or thousands of people.

 “Our primary objective is to establish a medical countermeasure that is safe, effective and simple to take, in the event we experience a shortage of medical personnel for the first 24 to 48 hours,” said Chen, a professor of Radiation Oncology at the University’s James P. Wilmot Cancer Center. “A post-radiation pill would be tremendously helpful.”

The contract was awarded by the Biomedical Advanced Research and Development Authority (BARDA), which develops and acquires medical countermeasures to chemical, biological, radiological or nuclear threats, as well as to pandemic flu and other infectious diseases. BARDA operates within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services.

High doses of radiation can be lethal to healthy cells in the bone marrow. Exposed individuals are at risk of two serious blood-related complications. The first, called neutropenia, (an abnormally low number of white cells), increases the likelihood of sepsis and death due to opportunistic infections.

While there are no products currently licensed to address the neutropenia associated with radiation exposure, based on experiences with cancer patients doctors have some options. For example, they can give medications to boost white blood cell production, antibiotics, fluids, and whole blood transfusions.

The second potential complication, however, called thrombocytopenia, is more difficult to manage. Thrombocytopenia is an abnormally low number of blood platelets, which increases the risk of death due to uncontrollable hemorrhaging, both internally and externally. Few options are available to treat thrombocytopenia and bleeding; platelet transfusions are costly and platelet supplies are limited. Evidence suggests that the most promising pathway to rescue or restore blood platelets is through the thrombopoietin (TPO) receptor.

In clinical trials, daily administration of eltrombopag in healthy and thrombocytopenic humans resulted in a dose-dependent increases in platelet counts in the peripheral blood within 1 to 2 weeks. GlaxoSmithKline is developing eltrombopag in a number of other conditions associated with thrombocytopenia.

GlaxoSmithKline is supplying University of Rochester with eltrombopag. The BARDA contract is the second award to go to the University of Rochester since the terrorism attacks on Sept. 11, 2001. Due to the Medical Center’s well-established track record of investigating the effects of radiation on the body, in 2005 the National Institutes of Health awarded the University $21 million, under the direction of principal investigator Paul Okunieff, M.D., for a series of projects to improve the country’s response to a possible radiological attack. As part of Okunieff’s program, Chen is also leading a collaborative effort to develop a blood test to rapidly measure an individual’s radiation exposure.

The BARDA contract required the University to meet special criteria governing laboratory research. The Good Laboratory Practice (GLP) principles, required by the FDA as well, are to ensure the consistency and reliability of results.

Key co-investigators include: J.H. David Wu, Ph.D., professor of Chemical Engineering and Biomedical Engineering; Jane Liesveld, M.D., professor of Hematology/Oncology and clinical director of the Samuel E. Durand Blood and Marrow Transplant Program; Bruce Fenton, Ph.D., professor of Radiation Oncology and Biomedical Engineering; Peter Keng, Ph.D., professor of Radiation Oncology; and Ollivier Hyrien, Ph.D, assistant professor of Biostatistics and Computational Biology.

The project also involves co-investigators Craig Jordan, Ph.D., professor of Biomedical Genetics and director of the Wilmot Cancer Center’s Translational Research for Hematologic Malignancies; Louis Constine, M.D., professor of Radiation Oncology; Gordon L. Phillips, M.D., professor of Hematology/Oncology and director of the Samuel E. Durand Blood and Marrow Transplant Program; and Okunieff, who is chair of Radiation Oncology. Katie Dawson, M.D., and Connie Erickson-Miller, Ph.D., of GlaxoSmithKline will serve as external advisors.

* Editor’s Note: Eltrombopag interacts with the transmembrane domain of the human TPO-R and initiates cascades similar, but not identical, to that of endogenous thrombopoietin (TPO), thus inducing proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. In clinical trials, daily administration of eltrombopag in healthy and thrombocytopenic humans resulted in a dose-dependent increase in platelet counts in the peripheral blood within one to two weeks. In clinical studies, the most common adverse events observed in patients taking eltrombopag were headache, common cold, and nausea. PROMACTA® (eltrombopag) was granted accelerated approval by the FDA on Nov. 20.  PROMACTA® is indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.   

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