Synthetic molecule for new asthma treatment

A novel molecule which prevents T-cells from coordinating asthma bought on by allergens has been identified by an international team of researchers. The findings, published in Proceedings of the National Academy of Sciences, could point towards a potent therapeutic agent to treat the chronic lung disease. In mouse models, researchers showed that a synthetic molecule, a sulphate monosaccharide, blocks the interaction between chemokine CCL20, a T-cell signalling protein, and heparin sulphate, a molecule that protects and immobilises CCL20 on epithelial cells in the lung. Blocking this interaction stalled the recruitment of the T-cells that trigger inflammation, and researchers showed this could be achieved when the model was administered intravenously and by inhalation. “We have identified a synthetic molecule, a sulphate monosaccharide, that inhibits the signal that recruits T-cells to the lungs to start and asthma attack,” said Minoru Fukuda, adjunct professor in the Tumour Mincroenvironment and Metastasis Program at Sandford-Burnham Medical Research Institute in America. “Heparan sulphate is critical as a receptor for chemokines, which activates leukocytes which adhere to endothelial cells. We have shown that upon abrogation of endothelial heparin sulphates, lymphocyte recruitment to lymph nodes is dramatically impaired,” Fukuda told Laboratory News. “In the current PNAS paper, we showed that inflammation in asthma also depends on T-cell recruitment to lung endothelial cells.  Moreover, novel 2,4-disulphate  L-iduronic acid interferes with this process by binding chemokine CCL20,  which is crucial for asthma inflammation in the lung.” The molecule substantially lessened asthma symptoms such as inflammation, mucus production and airway constriction, he added. Pulmonary inhalation of this new molecule may help reduce asthma symptoms by suppressing chemokine-mediated inflammatory responses. “We look forward to the further development of the molecule to treat millions of people who suffer from this chronic disease,” Fukuda said. “Future research directions are to determine if 2,4-disulfo L-iduronic acid attenuates inflammation where asthmatic response already took place and 2,4-disulffor L-iduronic acid is useful in asthma model of higher animals.” The work also included researchers from the Max Planck Institute for Colloids and Interfaces, the Free University of Berlin, UC San Diego and Shinsu University. www.pnas.org