, Jan. 20, 2012
/PRNewswire/ -- Carolus Therapeutics, Inc.
today announced the publication of preclinical data showing that CT-2009 disrupts heteromers formed by the platelet-derived chemokines CCL5 (RANTES) and CXCL4, thereby preventing lung damage in multiple mouse models of acute lung injury (ALI). The study, published online on the website of the American Journal of Respiratory and Critical Care Medicine (AJRCCM),
showed that CCL5-CXCL4 chemokine heteromers are associated with platelet-dependent recruitment of neutrophils, increased lung permeability and tissue damage.
Neutrophils are thought to be important disease effector cells in ALI as well as other respiratory conditions. Inhibiting these chemokine heteromers with CT-2009 strongly diminished recruitment of neutrophils to the lung, lung permeability changes, and tissue damage. In lung tissue samples from both human patients and mice with ALI, lung neutrophil counts were highly correlated with chemokine heteromer concentrations, providing strong support for the CT-2009 chemokine heteromer target having an important pathological role in ALI and translation of the mouse model results to human disease.
"There is a large unmet medical need for effective treatments for acute lung injury, as currently as many as 40 percent of patients die from the condition," said Christian Weber, M.D., Chair in Vascular Medicine and Director of the Institute for Cardiovascular Prevention at Ludwig-Maximilians-University (LMU) in Munich, Germany. "This study suggests that utilizing a drug such as CT-2009 to block the formation of these chemokine heteromers involved in the inflammatory pathway in acute lung injury carries much promise for treatment of the disease."
Gram-negative bacterial infections are the main cause of ALI, leading to lung neutrophil infiltration, permeability increases, deterioration of gas exchange, and lung damage. Despite all innovations in intensive care medicine, the mortality of ALI remains up to 40 percent.
The study by the group of Oliver Sohnlein, M.D., Ph.D., at LMU showed that the platelet-derived chemokines CCL5 and CXCL4 form heteromers in lung tissue samples from human patients and mice with ALI, positively correlating with neutrophil influx into the tissue as well as changes in lung permeability. Furthermore, disruption of these chemokine heteromers in lipopolysaccharide-, acid-, and sepsis-induced ALI abolished lung edema and tissue damage, revealing a casual contribution. Together, the data identify a novel function of these chemokine heteromers and predict that heteromer disruption with drug candidates such as CT-2009 may be effective as a therapeutic approach.
In the study, various antagonists were compared to determine the effect of each on platelet-related lung tissue damage. While antagonists to P-selectin and glycoprotein IIb/IIa, which play an essential role in the initial recruitment of white blood cells, did nothing to reduce edema and tissue destruction, both CT-2009 and antibodies to the platelet-derived chemokines CCL5 and CXCL4 diminished neutrophil recruitment and reduced edema and tissue damage.
CT-2009 is a selective chemokine heteromer inhibitor with potential therapeutic utility in respiratory, pulmonary, cardiovascular, renal, hepatic, and other indications. Initial focus with CT-2009 has been on idiopathic pulmonary fibrosis, pulmonary arterial hypertension, severe asthma, and chronic obstructive pulmonary disease. CT-2009 has demonstrated robust preclinical efficacy in a number of these indications and an excellent safety profile with no impairment of immune function. Carolus Therapeutics has plans for an IND filing for CT-2009 in third quarter of 2012.
About Carolus Therapeutics
Carolus Therapeutics, Inc. is a biopharmaceutical company developing innovative new drugs that will provide relief to patients suffering from a host of disorders triggered by acute and chronic inflammation. The clinical and commercialization focus of the company is on novel therapeutic strategies to noninvasively monitor and disrupt pro-inflammatory interactions of chemokines and prevent or reverse inflammation associated with a broad array of human diseases. The company's patented technology represents a promising advance in inflammation therapy where the underlying disease, as opposed to the symptoms, is treated without significant side effects. For more information about Carolus please visit www.carolustherapeutics.com
SOURCE Carolus Therapeutics, Inc.