MANHASSET, NY – One to five percent of people who undergo surgery for gastrointestintal problems experience a potentially life-threatening condition: a temporary loss of oxygen that can set in motion a rogue inflammatory response that can lead to organ failure.
Ping Wang, MD, a scientist at The Feinstein Institute for Medical Research in Manhasset, NY, is testing the benefits of an experimental medicine that can clear away dying cells and reduce the risk for ischemia reperfusion injury. In a lead study published in the American Journal of Respiratory Critical Care Medicine, Dr. Wang and his colleagues used an experimental medicine called MFG-E8 on the heels of ischemia and found that it significantly lowered the risk for ischemia reperfusion injury, a condition caused when blood flow to the organ is interrupted (during surgery, injury or disease) and then re-established. Normally, when tissue suffers from a temporary loss of oxygen, the body makes an unusual response when the oxygen starts to flow again. It sets off an inflammatory response. These inflammatory cells actually target tissue and can trigger multiple organ failure. The lung is most susceptible to this type of injury, which is why in humans it can be deadly.
MFG-8 blocked the acute lung injury in an animal model of ischemic reperfusion. Fifty percent of the animals exposed to MFG-8 survived, according to Dr. Wang. MFG-8 is a protein normally produced by the spleen to enhance clearance of dying cells. The Feinstein scientists made a recombinant human protein. The idea to use the protein emerged after their studies showed that MFG-8 levels drop markedly on the heels of ischemia reperfusion. Spleen cells just can’t produce enough of the substance to clean up the dead or dying cells. If the cells are not removed – and this cellular garbage continues to accumulate – this cell death (called necrosis) can cause acute lung injury.
They found that the medicine helped clear out 90 percent of the dead cells in the hard-hit lung. It also reduced inflammation at the site. And the most hopeful news was that half of the animals survived the injury. The work in the laboratory will continue to address questions that need answering: Will the protein be harmful to patients? How much will be enough to protect against organ failure?
Right now, there is no approved medicine to treat ischemic reperfusion. Dr. Wang said that there are 50,000 to 100,000 deaths a year related to this intestinal injury.
About The Feinstein Institute for Medical Research
Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson’s disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology, and medicinal chemistry. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs.