TLR4 Antagonist

About

Overview Invasive Gram-negative bacteria and necrotizing enterocolitis cause life threatening disease by stimulating intense cytokine-induced and neutrophil-mediated gut wall damage. Global antimicrobial resistance means that alternatives to antibiotics are urgently needed. Polypropyletherimine dendrimer glucosamine (DG) is a small, orally administered Toll-like receptor-4 (TLR4) antagonist to treat bacterial gastroenteritis by maintaining gut wall integrity and preventing sepsisinduced tissue damage. It acts locally on the gut wall and is not systemically absorbed.   Technology A team at Imperial College London, led by Professor Shaunak, has designed a dendrimer (DG) molecule that: DG protects the colon and rectum from pro-inflammatory cytokineinduced vasculitis and gut wall necrosis. This prevents tissue invasion by bacterial pathogens. Reduces colon CD4+ and CD8+ lymphocyte activation without disturbing the cytokine response in gut lymph nodes and blood. Significantly reduces severity of clinical disease. Preserves commensal bacteria and accelerates patient recovery time.   Development stage DG treatment was successfully tested in non-human primates for Shigella dysenteriae infection (no antibiotics) treatment. DG reduced diarrhoea by 54%, colon inflammation by 71%, and neutrophil infiltration rate by 75%.   Intellectual property The DG technology is protected by awarded patent in UK, Germany, France, US, India and China.