Date: 2014-09-04
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the annual European Respiratory Society International Congress in Munich and at the XXV International Complement Workshop in Rio de Janeiro
Company: Noxxon Pharma (Germany
Product: NOX-D19 (Spiegelmer® neutralizing the complement component C5a)
Action
mechanism: NOX-D19, a PEGylated L-RNA aptamer (Spiegelmer®) binds and neutralizes the complement fragment C5a, a major mediator of the complement system which is involved in the immune response against infections but also contributes to hyperinflammation, vascular barrier dysfunction, microcirculatory failure, and organ failure. Hypothetically the inhibition of C5a-signaling by NOX-D19 in pneumococcal pneumonia could prevent pulmonary vascular barrier failure and protect against extrapulmonary organ failure.
Disease: pneumococcal pneumonia-induced sepsis
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news: * On September 4, 2014, Noxxon Pharma announced that scientists of Charité - Universitätsmedizin Berlin and Noxxon Pharma are invited to present new preclinical data about effects of NOX-D19, a Spiegelmer® neutralizing the complement component C5a, in pneumococcal pneumonia-induced sepsis. The talks with the title “Neutralizing the Complement Component C5a Protects Against Lung Injury and Extrapulmonary Organ Injury in Pneumococcal Pneumonia-Induced Sepsis” will be held by Dr. Holger Mueller-Redetzky on Sunday, September 7 (Session 150) at the annual European Respiratory Society International Congress in Munich and by Dr. Axel Vater at the XXV International Complement Workshop in Rio de Janeiro on Tuesday, September 16 during Session V. The preclinical studies involving Streptococcus pneumoniae-infected mice were performed by Dr. Holger Mueller-Redetzky, Prof. Dr. Martin Witzenrath and coworkers at the Department of Infectious Diseases and Pulmonary Medicine at the Charité - Universitätsmedizin Berlin in cooperation with the Institute of Anatomy and Cell Biology and the Institute for Clinical and Experimental Surgery at the Faculty of Medicine of Saarland University in Homburg. Mice were infected with Streptococcus pneumoniae and the Spiegelmer® NOX-D19 was applied at the time of infection and 24 hours later. The pulmonary permeability, pulmonary and blood leukocyte count, and levels of IL-1β, G-CSF, KC and IL-6, bacterial load in lung, spleen and blood, markers of liver and kidney function (AST, BUN) and histological analyses of fibrin deposition and apoptosis in the liver were analyzed. 24 hours after infection, C5a levels reached a maximum in lung and blood. Lung failure and septic extrapulmonary organ injury developed within 48 hours post infection, as well as apoptosis of hepatocytes and microcirculatory failure. In contrast, in mice that received NOX-D19, neutralization of the pro-inflammatory factor C5a attenuated pulmonary permeability and reduced blood cytokine levels. Furthermore protection from liver injury was observed. The senior investigator of the study Prof. Dr. Martin Witzenrath from from Charité - Universitätsmedizin Berlin, concluded: “These first results in animal models are very promising. NOX-D19 seems to effectively neutralize C5a and have an effect on the overwhelming immune response that leads to unnecessary damage. NOX-D19 could thus give protection against lung and extra-pulmonary organ failure in pneumococcal pneumonia-induced sepsis and may offer an important adjuvant treatment strategy for improved survival in pneumococcal sepsis.”
