Intravenous gene therapy protects normal tissue of mice during whole-body radiation
PHILADELHIA, Nov. 7 -- Gene therapy administered intravenously could be used as an agent to protect vital organs and tissues from the effects of ionizing radiation in the event of large-scale exposure from a radiological or nuclear bomb, according to an animal study presented today by University of Pittsburgh researchers at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) in Philadelphia.
"Ionizing radiation can be extremely damaging to cells, tissues, organs and organ systems," said Joel S. Greenberger, M.D., professor and chairman department of radiation oncology, University of Pittsburgh School of Medicine. "In previous studies, we demonstrated that gene therapy can be both swallowed in pill form and inhaled through a nebulizer prior to radiation exposure to protect healthy tissues from damage. In this study, we found that the same therapy administered intravenously also offers protection during exposure to whole-body irradiation." Dr. Greenberger added that intravenous administration could potentially offer wide-reaching protection to the public in the event of a terrorist attack since experts believe a significant number of the population would die within 30 days of receiving a large dose of radiation to the entire body.
In the study, mice were used to test the protective effects of manganese superoxide dismutase plasmid liposome (MnSOD-PL) gene therapy on the bone marrow during whole-body irradiation. The researchers found that in a control group of mice that received an initial 9 Gy dose of radiation there was 80 percent survival at 30 days compared to 93.3 percent survival during the same length of time for an experimental group of mice that were injected with MnSOD-PL prior to irradiation. As the level of radiation exposure was increased, survival rates in the mice injected with MnSOD-PL prior to exposure increased significantly. For example, at 9.5 Gy, mice in the control group had a survival rate of 53 percent, while mice in the experimental group had a survival rate of 87 percent. Following irradiation to 9.75 Gy, only 12.5 percent of the mice in the control group survived, while 75 percent of the MnSOD-PL group survived.
"Intravenous administration of gene therapy appears to prevent the damaging effects of radiation, suggesting it is a viable delivery method," said Dr. Greenberger. "Future clinical studies will tell us whether this therapy can protect people from the deadly effects of radiation."
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The study's co-authors include Michael W. Epperly, Ph.D., and Yunyun Niu, Ph.D., both with the department of radiation oncology at the University of Pittsburgh School of Medicine. The study was funded by a $10 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to the University of Pittsburgh School of Medicine in 2005 to create a Center for Medical Countermeasures Against Radiation.
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