Acute Organ Failure

CBLI’s finding that Protectans are able to prevent death of normal cells in the face of stresses that normally induce apoptosis suggests a wide range of potential applications for these compounds. In addition to radiation exposure, another type of stress that leads to tissue damage through apoptosis of normal, non-cancerous cells is the ischemia (limited blood flow leading to local hypoxia) that occurs during acute medical conditions such as stroke, heart attack and renal failure.

CBLI researchers in collaboration with investigators from the Cleveland Clinic have demonstrated that injection of Protectan CBLB502, an optimized derivative of bacterial flagellin, effectively prevents acute renal failure and subsequent death in a mouse model of ischemia-reperfusion renal injury. Thus, CBLI expects that this class of drugs will be useful in limiting the tissue damage associated with a number of different acute organ failure scenarios. Pre-clinical studies aimed at validating this hypothesis are ongoing. The anti-ischemia effect of CBLB502 also has a potentially important defense application. The compound is being tested for its ability to reduce tissue damage associated with the use of tourniquets to prevent excessive bleeding from wounded limbs. If effective in this scenario, CBLB502 could allow significantly broader use of tourniquets, which has been limited by the high risk of limb loss due to prolonged tissue hypoxia. Systemic and local effects of tourniquet use are described in http://www.jbjs.org.uk/cgi/reprint/62-B/3/385.pdf.