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Joel S. Greenberger, M.D.

Joel S. Greenberger, M.D.

University of Pittsburgh Schools of the Health Sciences

Gene Therapy Successfully Protects Mice From The Damaging Effects Of Whole-Body Irradiation

Dirty Bomb Antidote?

BALTIMORE, June 3, 2006University of Pittsburgh School of Medicine researchers have successfully protected mice against the damaging effects that radiation can have on bone marrow using gene therapy. Based on these results, the researchers believe this approach may be able to protect first responders in the event of a radiological accident or the detonation of a crude radiological weapon, or “dirty bomb.” The findings are being presented at the American Society of Gene Therapy annual meeting in Baltimore, May 31 to June 4.

Since the events of Sept.11, there has been growing concern that terrorists may use a dirty bomb—a conventional explosive wrapped in radiological material—or attack a nuclear power facility to disperse high-dose radiation across a populated area. Experts believe a significant number of the population would die within 30 days of exposure to a high dose of radiation from such an event, which has prompted the federal government to fund efforts to develop medical interventions against radiological and nuclear threats.

In this study, Pitt researchers used gene therapy to deliver the compound manganese superoxide dismutase-plasmid liposome (MnSOD-PL) to the cells of female mice. Twenty-four hours later, groups of mice that received the treatment and control mice that did not were exposed to varying doses of whole body radiation. Following irradiation, the mice were weighed daily and observed for signs of irradiation-induced damage to their bone marrow. Control mice irradiated at the higher doses lost weight and died fairly rapidly due to bone marrow damage. In contrast, mice treated with the MnSOD-PL gene therapy showed no changes in body weight, had little bone-marrow damage, and lived longer compared to the control irradiated mice.

According to corresponding author Joel S. Greenberger, M.D., professor and chair of the department of radiation oncology and co-director of the Lung Cancer Center at the University of Pittsburgh Cancer Institute, the results of this study have implications not only for first responders to a radiological accident or attack but also to anyone else who might be exposed.

“This treatment is probably most effective when it is administered before exposure to radiation, as would be the case for first responders entering a radioactive environment. However, we have shown that it does have post-exposure, or mitigation, properties when we’ve administered it as a supplement to bone marrow transplantation. So, it also may be effective for treating people who have already been exposed to a radioactive event,” he said.

This work was supported by the National Institute of Allergy and Infectious Diseases as part of its research program on Medical Countermeasures Against Radiological and Nuclear Threats. Others involved in this study include Michael W. Epperly, Ph.D., and Yunyun Niu, M.D., department of radiation oncology, University of Pittsburgh Cancer Institute.

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