Antibody therapy prevents gastrointestinal damage following radiation exposure in mice

April 4, 2012

A new study offers the first evidence of a drug capable of preventing lethal damage to the gastrointestinal (GI) tract caused by exposure to high levels of ionizing radiation, such as those occurring during a nuclear incident. There are currently no FDA-approved treatments or prophylactics available to manage the condition, known as radiation gastrointestinal syndrome (RGS), which is associated with weight loss, vomiting, diarrhea, dehydration, systemic infection, and – in extreme cases – septic shock and death.

The research was conducted in mice by investigators at Memorial Sloan-Kettering Cancer Center and The University of Texas MD Anderson Cancer Center and will be published in the May 2012 issue of The Journal of Clinical Investigation.

The GI system is maintained through the continuous infusion of epithelial cells produced by specialized stem cells located in gland-like structures called crypts found in the epithelial lining of the small intestines and colon. High-dose irradiation kills these stem cells and destroys the protective epithelial barrier, or mucosa, resulting in onset of RGS within days of exposure.

According to the study, administration of a drug called 2A2 anti-ceramide antibody inhibited cell death (apoptosis) in blood vessels within the and improved 90-day survival from 0 percent to 80 percent among mice exposed to 15 Gy whole-body irradiation.

"We discovered that using this monoclonal antibody to inhibit blood vessel damage and dysfunction led to a dose-dependent increase in the number of surviving stem cells, which are highly active and responsible for repopulation of the damaged GI epithelium," said the study's corresponding author Richard N. Kolesnick, MD, a member of Memorial Sloan-Kettering's Molecular Pharmacology and Chemistry Program whose laboratory conducted the research experiments.

Developed by investigators at MD Anderson, the drug works by interfering with ceramide — a lipid molecule that plays a role in apoptosis — generated on the surface of the endothelial cells that make up the smallest blood vessels of a tumor.

The US Department of Health and Human Services has placed significant emphasis on the development and deployment of new therapies and countermeasures to protect first responders, military personnel, and others who are required to enter into areas of potential radiation contamination. Dr. Kolesnick and colleagues are working to develop anti-ceramide antibody as an agent used not only to protect against the damaging effects of radiation prior to exposure, but also to mitigate those effects after exposure.

Explore further: Probiotic protects intestine from radiation injury

Related Stories

Probiotic protects intestine from radiation injury

November 16, 2011
Scientists at Washington University School of Medicine in St. Louis have shown that taking a probiotic before radiation therapy can protect the intestine from damage — at least in mice.

Systemic tumor disappearance following local radiation treatment reported in metastatic melanoma patient

March 7, 2012
A rarely seen phenomenon in cancer patients — in which focused radiation to the site of one tumor is associated with the disappearance of metastatic tumors all over the body — has been reported in a patient with ...

Recommended for you

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.