The cost of drug discovery and development has been skyrocketing over the past decade, yet the number of new drug approvals has fallen. Scientists are looking into new technologies and strategies to meet this challenge. Drug repositioning is one of such strategies and has been growing in importance in the last few years. On July 29, 2011, Journal of Immunology published online the new progress of a collaborative research between Tongji University and Shanghai Institute of Materia Medica (SIMM) about the new use of old drugs.
Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system and is one of the foremost causes of nontraumatic neurological disability in young adults. Under the supervision of Dr. XIE Xin, young scientists from Tongji University (WANG Liefeng, DU Changshen and et al.) discovered that CysLT1, a G protein-coupled receptor, is up-regulated in the immune tissue and spinal cord of experimental autoimmune encephalomyelitis (EAE) mice. CysLT1 is a known drug target. Antagonists targeting CysLT1, such as montelukast and zafirlukast, are currently marketed as anti-asthmatic drugs. Montelukast (trade name Singulair) is among the 20 top selling drugs worldwide. But whether CysLT1 is involved in EAE or MS has never been reported. They found that montelukast and zafirlukast can effectively block the CNS infiltration of inflammatory cells and thus reduce the incidence, peak severity, and cumulative disease scores. Further study indicated that CysLT1 signaling might affect the pathogenesis of EAE by increasing the permeability of blood-brain barrier (BBB) and inducing chemotaxis of T cells, which can be block by CysLT1 antagonists. These findings indicate that the anti-asthmatic drugs against CysLT1 can also be used to treat multiple sclerosis.
Dr. XIE Xin is a Principle Investigator from Shanghai Institute of Materia Medica (SIMM), CAS, and the Head of Assay Development Department II of the National Center for Drug Screening. She is also an Adjunct Professor of School of Life Sciences and Technology, Tongji University. Her research is mainly focused on GPCR-based drug discovery and chemical biology of stem cells. Her group recently reported that anti-psychotic drug LiCl can greatly promote iPSC induction (Cell Research, 2011）。
This work was supported by grants from the National Natural Science Foundation of China, Ministry of Science and Technology of China, and Shanghai Commission of Science and Technology.
Original Article：http://www.jimmunol.org/content/early/2011/07/29/jimmunol.1100333.full.pdf+html

(Image by SIMM)

A-D, CysLT1 antagonists (montelukast and zafirlukast) alleviate clinical scores in EAE (black arrows indicate the starting point of drug application). E, HE staining indicates montelukast reduces immune cell infiltration into the spinal cord of EAE mice. F, Luxol fast blue staining indicates montelukast prevents demyelination of the spinal cord in EAE mice.