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DOD grant explores new drugs to thwart impact of trauma, stroke, and cardiac arrest

September 07, 2016

A $2.3 million Department of Defense grant will help neuroscientists develop new treatments for the emergency room and the battlefield. The research will focus on the development of new therapies that could help protect brain and other at risk organs following a trauma, heart attack, or stroke.

"While we have made significant progress in our ability to restore blood flow after stroke or cardiac arrest, the medical community does not have drugs at its disposal to prevent the secondary damage that occurs after these events," said University of Rochester Medical Center neurologist Marc Halterman, M.D., Ph.D., the principal investigator of the study. "This grant will further our research on a promising class of drugs that possess both anti-inflammatory and cytoprotective properties that we believe will be suitable for use in both military and emergency conditions."

The project was developed in collaboration with a team of synthetic antibiotic chemists in Salt Lake City, led by Mark Nelson, Ph.D. who will serve as the principal investigator for the sub-award to Echelon Biosciences.

The new grant will enable Halterman and Nelson to synthesize and test drugs to protect the brain and other organs in the body from ischemia and reperfusion injury (IRI). When the body is subject to blunt trauma with acute blood loss, cardiac arrest or stroke, the direct cellular injury that occurs due to inadequate blood supply (ischemia) is often compounded by a delayed wave of tissue damage caused by the accumulation of free radicals and activation of the immune system which can continue long after the blood flow restarts (reperfusion).

When IRI occurs in the brain, heart, kidneys, and other susceptible organs, the damage can become permanent, debilitating, and potentially fatal. There are currently no effective drugs used to reduce the collateral damage caused by IRI.

Their research will focus on a family of antibiotic drugs called tetracyclines. While these drugs have been around for more than 60 years and are most commonly used to treat bacterial infections, they also possess potent anti-inflammatory and neuroprotective properties.

Halterman and Nelson have identified a compound that shows promise in preventing damage in tissue samples and animal models of stroke and cardiac arrest. This compound - designated EBI-2114 - is also highly stable, meaning it maintains its integrity and effectiveness even under adverse conditions, such as on a battlefield, during a natural disaster, or for emergency care. The compound will also be designed to be inactive against bacteria, sparing the patient of the possibility of developing antibiotic resistant infections.

University of Rochester Medical Center

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