New Findings May Lead to Enhanced Treatments for Multiple Sclerosis and Autoimmune Inflammation

A multidisciplinary research team of scientists from Singapore has made a breakthrough discovery of a new type of immune cells that may help in the development of a future treatment for multiple sclerosis (MS).

Led by Prof. Xin-Yuan Fu, senior lead investigator from CSI Singapore and professor at the department of biochemistry at the National University of Singapore (NUS) Yong Loo Lin School of Medicine (Singapore), and Dr. Wanqiang Sheng, postdoctoral fellow at CSI Singapore, the scientists discovered that a new type of immune T helper cells called TH-GM cells play a crucial role in the immune system and pathogenesis of neuronal inflammation. The findings offer insights into a potential new avenue for therapeutic intervention, which can be used independently or combined with other treatment options to optimize outcomes in the treatment of MS.

Working with Dr. Yong-Liang Zhang, from the department of microbiology at the NUS Yong Loo Lin School of Medicine, Prof. Fu and his team demonstrated that STAT5, a member of the STAT family of proteins, programs TH-GM and triggers the immune response to an autoantigen in responding to a signal from an interleukin, IL-7, causing neuroinflammation, pathogenesis and damage in the central nervous system. Blocking IL-7 or STAT5 would provide a substantial therapeutic benefit for this disease. The study’s findings were published online November 21, 2014, in the journal Cell Research.

MS is the most prevalent autoimmune disease of the central nervous system, affecting about 2.5 million people worldwide, with cases showing a higher prevalence in Northern Europe. In spite of many years of research, the causes of MS are mostly not known and the disease remains incurable.

This study provides vital clues into the processes behind MS. Dr. Richard Flavell, chair of the department of immunology at Yale University (New Haven, CT, USA), and a world leader in the immunology field, noted that the findings from the study may now provide a mechanistic link between IL-7/STAT5-mediated signaling and T helper cell-mediated pathogenicity.

The STAT family of proteins and their signaling pathway (called JAK-STAT) were first discovered by Prof. Fu and his colleagues in 1992. Disturbance of this pathway was shown to be a major cause for many kinds of inflammatory disorders. Innovative drugs interfering with JAK-STAT have since been approved in the United States, Europe, and Singapore for the treatment of numerous diseases, and annual sales of medicines involving JAK-STAT are expected to exceed USD 1.6 billion in 2016. The newly discovered IL-7-STAT5 by Prof. Fu and his team in neuroinflammation considerably expands this line of medical research, development, and therapeutic intervention in a variety of major diseases.

Prof. Fu and collegues are now researching the physiologic function of TH-GM to further the development of therapy for various human autoimmune diseases.

Related Links:
CSI Singapore
National University of Singapore Yong Loo Lin School of Medicine