Researchers from CalciMedica, Inc. and the University of Liverpool today announced the publication of a paper describing positive effects of calcium release-activated calcium (CRAC) channel inhibitors in animal models of acute pancreatitis. The paper, titled "Inhibitors of ORAI1 prevent cytosolic calcium-associated injury of human pancreatic acinar cells and acute pancreatitis in 3 mouse models" appears in the August edition of the journal Gastroenterology.
The paper shows that particular CRAC channel inhibitors interacting with the Orai1 protein, a key component of the CRAC channel found in pancreatic acinar cells, have strong activity on all measures of disease and pathology in three different and widely accepted animal models of acute pancreatitis. Of particular translational significance is the finding of protective effects of Orai1 inhibition on human pancreatic acinar cells exposed to different physiologically relevant pancreatic toxins. The two compounds studied, one from CalciMedica and the other from GSK, differ structurally but had similar activity in the animal models, and the CalciMedica compound, CM_128, is advancing toward clinical studies.
Dr. Robert Sutton, MD Professor of Surgery and Director of the NIHR Liverpool Pancreas Biomedical Research Unit at the Royal Liverpool University Hospital and senior author of the paper, said "This work highlights an exciting approach to the treatment of acute pancreatitis, a serious disease with significant morbidity and mortality. Tens of thousands of people present at the Emergency Department every year with acute pancreatitis, and there is no disease-modifying therapy available."
Dr. Sutton continued, "While essentially everyone with acute pancreatitis is admitted to the hospital, the majority, thankfully, recover over the course of a week or two without major incident. Still, there are some who have a severe course, often with extensive stays in the hospital or intensive care unit, and there is little we can offer them except supportive care and surgical intervention if required."
"An agent that actually reduces the impact of the disease process would be a significant step forward in this field, and I am excited by these results. We are most grateful to the UK Medical Research Council (MRC), the National Institute for Health Research (NIHR), the research charity CORE and to CalciMedica for supporting these studies," Dr. Sutton said.
Michael Dunn, Senior Vice President, Corp. Dev. at CalciMedica, said, "Dr. Sutton and his team, as well as the scientists at GSK, have been great collaborators. We are very encouraged by the results, and believe a CRAC channel inhibitor can successfully impact this disease, with substantial benefit to patients. We hope to translate these findings into the first effective therapeutic for acute pancreatitis, and plan to start clinical studies early next year."