Description:
Anti-inflammatory action through chromatin modulation
Market Need
Inflammation is a hallmark of diseases such as sepsis, endotoxaemia, arthritis, acute respiratory disease, and multiple organ failure. Steroidal and non-steroidal anti-inflammatory medications (NSAIDS) both carry different risks, including risk of infection due to immune suppression with steroid use and increased risk of heart attack or stroke that has recently been highlighted by the FDA in regards to NSAIDs. Other anti-inflammatory drugs, such as anti-TNF-alpha antibodies, can be costly and not appropriate for all indications. Thus, it is of interest to discover new pathways by which inflammation can be mediated that would have less side effects and could be translated cost effectively.
Technology Overview
Recently it has been shown that high mobility group box 1 (HMGB1), a chromatin organizer protein, is released into the cytosol and mediates inflammation in response to stress in many of inflammatory disease states. Thus, blocking HMGB1 activity could provide a novel pathway to target inflammation. The Weitzman lab has discovered that protein VII can bind and neutralize HMGB1 and associated inflammatory markers. The discovery stems from the labs interest in how viruses interact with host DNA in order to evade detection. The inventors have shown that the virally-encoded protein VII can bind HMGB1 to alter cellular host chromatin state and decrease neutrophil count in bronchoaveolar lavage fluid in a mouse model of inflammation. Future plans include identifying the necessary amino acids in protein VII that are required to have this anti-inflammatory effect.
Advantages
• Chromatin rearrangements could lead to a longer lasting anti-inflammatory effect
• Potential for small molecule or small peptide therapeutic
Application
• Treatment for sepsis, endotoxaemia, arthritis, acute respiratory disease, and multiple organ failure
• Treatment for diseases which are caused by inflammation
Stage of Development: In vivo proof of concept