Neurology

Patient sample and mouse studies suggest inhibiting HMGB1 or reactive oxygen species (ROS) could help treat necrotizing enterocolitis-associated cognitive impairments. In infants with necrotizing enterocolitis, serum levels of HMGB1 and brain levels of ROS were higher than in healthy infants. In a mouse model of necrotizing enterocolitis, intestinal epithelium-specific HMGB1 knockout increased myelin basic protein (MBP) levels in the hippocampus and periventricular region of the brain compared with normal expression. Also in the mouse model, an activated microglia-targeting polyamidoamine dendrimer conjugated to the antioxidant N-acetyl cysteine decreased cognitive deficits and brain levels of ROS compared with no treatment. Next steps include testing HMGB1 or ROS inhibition in infants with necrotizing enterocolitis.

Applied Immunotherapeutics Inc. and Feinstein Institute for Medical Research have two small molecule inhibitors of HMGB1, K557 and K883, in preclinical testing for autoimmune diseases...