Targeting Ryk-signaling to attenuate multiple sclerosis by promoting oligodendrocyte differentiation and myelination

2015-07-30Multiple Sclerosis (MS) is a CNS degenerative disease. It is one of the most common chronic disabling CNS disease in young adults. In MS, oligodendrocytes(OLs) loss is the most important character. MS is also recognized as an autoimmune disease. Recent therapies are mainly focusing on immunomodulation and remyelination. Remyelination happens naturally, however it can be avoided in CNS. We selected three small inhibitors working towards Ryk signaling pathway, in order to stimulate remyelination. However, drug screening for MS has been strongly obstructed due to limited resources of OLs as well as a proper cell culture system. So we developed a method to differentiate neural stem cells (NSCs) into matured OLs, and we also developed an in vitro OLs culture system. Using this system, we tested three drug candidates (17-AAG, DAPT and Celastrol) for gradient concentration. Results showed the amount and ratio of OLs significantly increased. Immunomodulation is a method that can only reduce the velocity of disease progression, they does not have effects on restoring existed lesions. Remyelination using oral drugs seems to be a promising future of MS therapy, while stem cell based techniques are still far away