Development of ACE Inhibitors to Treat Radiation Injury
The Medical College of Wisconsin (MCW) has received a five year, $2.6 million grant from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases to develop the use of an ACE inhibitor, lisinopril, to mitigate radiation injuries in multiple organs.
Meetha Medhora, PhD, professor of radiation oncology at MCW, is the primary investigator of the grant.
Dr. Medhora and colleagues are attempting to repurpose ACE (angiotensin-converting enzyme) inhibitors,which are typically prescribed to treat hypertension, to mitigate radiation injuries. Investigators at MCW and other institutions have demonstrated that incidental use of these drugs by irradiated cancer patients decreased lung radiation injury. In rat models, Dr. Medhora, along with Dr. Eric Cohen, Dr. John Moulder and Brian Fish have demonstrated that the effects of radiation on kidneys were mitigated when the animals received ACE inhibitors a week after exposure.
In this study, researchers will study lisinopril under conditions simulating a nuclear accident or radiological event—and will test lisinopril in combination with countermeasures proposed for the Strategic National Stockpile for use against acute radiation syndromes. Dr. Medhora’s team in collaboration with the University of Massachusetts, Lowell, will also test lisinopril for mitigation after exposure to different types of radiation including X-rays, neutrons and gamma rays.
A second aim of the grant is to study the mechanisms of action of ACE inhibitors at the molecular, cellular and whole organ levels.