NEWS CELSUS QUALIFIES FOR A THIRD NIH GRANT FOR DRUG DEVELOPMENT.02/28/03 -- Celsus Laboratories, Inc. (Cincinnati OH) announces it received a $ 224,000 phase I research grant from the National Heart, Lung, and Blood Institute for a preclinical study of the drug, Intimatan. Included will be research in a revascularization model of ischemic reperfusion injury during cardiopulmonary bypass (CPB) surgery by Emory University. The new study is designed to further test the efficacy of Intimatan as a replacement for heparin in cardiac surgery. Intimatan is a patented heparin cofactor II agonist, comprising a disaccharide sequence of repeating L-iduronic acid N-acetyl-D-galactosamine 4,6-O-disulfate joined by 1,3 and 1,4 linkages. This naturally-occurring, but rare, disaccharide may be prepared by synthesis or by site-selective 6-O-sulfation of native dermatan sulfate. Current practice for CPB surgery requires high dose heparin (400 U/kg) to maintain patency of the extracorporeal circuits during flow. However, thrombin bound to the fibrin clot, vessel wall and biomaterial surfaces is typically resistant to inhibition by heparin. In comparison with heparin, using a pig model of CPB, Intimatan maintained extracorporeal patency at one tenth the anticoagulant dose; generated a 4-fold lower activated clotting time (ACT); reduced chest wall bleeding more than 2-fold; and did not induce thrombin rebound or require neutralization post-procedure. In contrast, the use of heparin requires post surgical neutralization which often results in heparin-protamine-complex-induced complement activation contributing to postoperative edema, tissue injury and neural deficits. Other preclinical pharmacology studies, thus far, have shown Intimatan to be an inhibitor of surface-bound thrombin, complement activation, and neointimal hyperplasia in models of restenosis injury. In the treatment of acute coronary thrombosis, Intimatan reduces the dose of platelet GPIIb/IIIa inhibitors required to block coronary thrombosis in vivo and prevents recurrent coronary artery thrombosis in the canine following adjuvant thrombolysis with tissue plasminogen activator. It completely prevents primary arterial and venous thromboses in the canine model of electrolytic injury. Intimatan also protects against inflammation damage to the isolated perfused rabbit heart and may thus protect against the ravages of ischemic-reperfusion injury in myocardial infarction and stroke. Furthermore, Intimatan blocks the activation of platelets of patients with heparin-induced thrombocytopenia (HIT) caused by heparin allergy. As a HIT antagonist, Intimatan may benefit high-risk cardiac patients who experience thrombosis due to heparin exposure. Case Van Gorp, the president and founder of Celsus, is a co-inventor of Intimatan. Dr. Alan D. Cardin, vice president of Celsus is the principal investigator for this grant. He is well known for his research into heparin-binding proteins, often referred to as "Cardin Clusters". These two principals of Celsus have more than 45 years of combined experience in the development and manufacture of heparin-like compounds.
For information, please contact Alan D. Cardin, Ph.D. (513) 772-8130
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