University of Virginia Health System

DATA ON ADENOSINE'S AFFECT ON SPINAL CORD TRAUMA PRESENTED AT SCIENTIFIC MEETINGS

Researchers at the University of Virginia School of Medicine reported today that an adenosine analog may reduce damage to the spinal cord as a result of trauma. The findings were presented by Dr. David C. Cassada, surgical fellow in the U.Va. Division of Thoracic Cardiovascular Surgery, at the 15th Annual Scientific Meeting of the Eastern Association for the Surgery of Trauma in Orlando, Fla.

The findings focus on the use of a compound designed by Dr. Joel Linden, professor of medicine and synthesized by Dr. Timothy Macdonald , professor of chemistry, both faculty members at U.Va. The new compound was licensed to Adenosine Therapeutics, LLC, a Charlottesville-based biotechnology company that is seeking to develop the compound for future use.

The team of researchers at U.Va. discovered that adenosine analogs protect the spinal cords of animals from injury resulting from either traumatic injury or from a temporary loss of blood flow to the spine called ischemia that occurs in certain types of vascular surgery. The results of the study suggest that traumatic or ischemic spinal cord injuries gradually worsen due to inflammation. Treatment with the adenosine compound suppresses that inflammation response. The potential application to humans would be in a patient that experiences trauma to the spinal cord or possibly patients who suffer ischemic damage to the spinal cord during aortic surgery.

The Adenosine Therapeutics compound reduces neurological impairment when given quickly to animals following spinal cord trauma. The same compound also decreases paralysis after spinal cord ischemia, Cassada said.

The findings of the current study indicate that the administration of a systemic adenosine agonist (A2A) for three hours, beginning 10 minutes after blunt spinal cord trauma, partially reduces lower extremity impairment in an animal model for spinal cord injury. There is significant neurological functional outcome that is preserved for at least 48 hours after injury.

According to the study, the precise mechanisms for the efficacy of A2A adenosine receptor activation remains obscure, but effects on several different types of inflammatory cells may participate in the protection. Additional studies will be necessary to determine if protection by A2A agonists occurs if treatment is delayed beyond 10 minutes after injury or if any additional benefit to be gained by continuous infusion of the drug for longer intervals.

The current standard of care for the treatment of spinal cord trauma is steroid-based, which produce anti-inflammatory effects on many tissues. It will be interesting to determine in additional experiments if there is additive or prolong protection afforded by a combination of A2A agonists and steroids following spinal cord injury, Cassada said.

Adenosine has been a focus of interest at U.Va. for several decades. The late Dr. Robert Berne first recognized it as an important regulator of coronary blood flow and cardiac output in the early 1960s. He introduced adenosine as a therapeutic agent in the treatment of certain heart arrhythmias and his work produced a new cardiac drug, Adenocard, now used in ambulances and emergency rooms across the country.

January 17, 2002