April 12, 2012
Researchers Find Potential Drug for Preventing, Treating Radiation Sickness
BY Scott Merville
An antibody created at MD Anderson blocks the life-threatening gastrointestinal damage caused by high levels of radiation - so far in mice, but with potential for human use.
"If additional research confirms these findings, the antibody we call 2A2 could be deployed both for military and civilian use to prevent radiation sickness," says Wadih Arap, M.D., Ph.D., professor in MD Anderson's David H. Koch Center for Applied Research of Genitourinary Cancers.
Radiation gastrointestinal syndrome occurs after radiation exposure destroys specialized cells called crypt or villus units that generate the epithelial cells that line the GI tract. With the protective lining compromised, patients suffer vomiting, diarrhea, dehydration, systemic infection and in extreme cases, septic shock and death.
Research by Richard Kolesnick, M.D., and colleagues at Memorial Sloan-Kettering Cancer Center in New York found that a protein called ceramide is a central player in this radiation-induced destruction.
Irradiation causes ceramide, a lipid protein that triggers programmed cell death, to gather on the surface of blood vessels that serve the GI lining and order those cells to commit suicide, or apoptosis.
Arap and Renata Pasqualini, Ph.D., also professor in the Koch Center and colleagues tackled the problem of developing an antibody to block ceramide. "It was technically challenging to generate, produce, and quality-control. It is a timely scientific and medical work given the events following the tragic nuclear disaster after the earthquake and tsunami in Japan," says Pasqualini. "As such, it epitomizes the sense of purpose and resilience along with superior know-how and skill of the investigators within our group."
In experiments at Memorial Sloan-Kettering, 12 of 15 mice (80%) given the antibody before radiation exposure survived for more than 100 days. All 18 untreated mice died within eight days.
Preliminary research indicates that treating mice after exposure also conferred a survival benefit, Arap notes, so it could be used as treatment as well as a preventive agent.
And there's interest in examining its potential for protecting cancer patients from the damaging effects of radiation therapy.
MD Anderson and Memorial Sloan-Kettering have an agreement to develop the drug commercially.
"We were delighted by this productive collaboration with our colleagues at Memorial Sloan-Kettering Cancer Center. In going forward, we hope that this work will form the mechanistic basis and ultimately provide a new drug approach to prevent and mitigate human deaths from radiation exposure in accidental, medical, bioterrorism, or military settings" Arap says.
Research paper in the Journal of Clinical Investigation Houston Chronicle story