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December 8, 2005

Radiation countermeasures center established

Experts believe a significant number of the population would die within 30 days of receiving a dose of radiation to the entire body from a “dirty bomb,” prompting the federal government to fund a new effort to develop medical interventions against radiological and nuclear threats. As part of this effort, the National Institute of Allergy and Infectious Diseases (NIAID) has awarded $10 million to the Pitt School of Medicine to create a Center for Medical Countermeasures Against Radiation.

The Pitt center is one of eight being established and funded nationwide by NIAID over the next five years and includes specialized facilities, or cores, in animal models, drug discovery, biostatistics, radiobiological stabilization, pilot research projects and training and education.

The new center will develop and test small molecules and mechanisms that may help protect vital organs and tissues from the lethal effects of ionizing radiation in the event of a large-scale terrorist attack.

Joel Greenberger, principal investigator of the grant and professor of radiation oncology at the medical school, and his team are examining the administration of a gene therapy agent called manganese superoxide dismutase plasmid liposome (MnSOD-PL) that has offered significant protection to specific organs such as the esophagus and normal lung in mice treated with radiation for non-small cell lung cancer. It is currently being tested in human clinical trials to protect the esophagus in patients receiving radiation therapy for lung cancer.

While damage to normal tissues during radiation therapy has been a major limitation to the effective treatment of lung cancer, MnSOD-PL has been used successfully in animal models to protect healthy tissues.

Greenberger seeks to bolster the protective capabilities of MnSOD-PL by supplementing its administration with novel small molecules and radio-protective drugs that could enable it to be delivered systemically throughout the body, potentially offering protection in the event that the entire body is irradiated at once.

In other projects, the team is focusing on the vital role that damage to mitochondria, principal sites in cells where energy is produced, plays in the body’s response to radiation. They are examining ways to stabilize important antioxidants that become depleted by radiation, thus securing a substance in the mitochondria called cytochrome C.

The center also will examine how to protect the mitochondria’s electron transport chain from becoming destabilized by looking at the changes that occur in mitochondria in the first few hours after radiation exposure.

Co-investigators include Michael Epperly, Richard Chaillet, Stefan Schlatt, Prabir Ray and John Lazo, School of Medicine; Valerian Kagan, Andrew Amoscato, James Peterson and Linda Pearce, Graduate School of Public Health; Peter Wipf, Department of Chemistry, and James Schlesselman, Hong Wang and Douglas Potter, University of Pittsburgh Cancer Institute.

Filed under: Feature,Volume 38 Issue 8

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