Development of glycomolecules as novel therapeutics for the treatment of multiple sclerosis

Multiple sclerosis (MS) is a major cause of persistent disability. One of the characteristic features of MS is a loss of the insulating myelin sheath around nerve processes known as axons and the subsequent relative failure to remyelinate the demyelinated axons. A key pathological feature of MS lesions is the presence of reactive astrocytes which have been proposed to modify the ability of the myelinating capacity of the environment. Reactive astrocytes, become enlarged, proliferate, change shape and secrete many factors. The mechanisms by which astrocytes become reactive are not known. However, recently we have identified that the level of sulphated heparan sulphates (HS) around astrocytes can affect their ability to become reactive. Moreover, we have previously shown that HS modified to have reduced levels of sulphation not only prevents characteristics of astrocyte reactivity but also can promote myelination and nerve outgrowth in mixed neural cells in a Petri dish, properties important in the repair of MS. The aim of the proposed research is to identify novel specific therapeutic targets for the treatment of MS based on previous observations that modified heparan sulphate and related molecules (glycomolecules) with reduced levels of sulphation can influence many aspects of CNS repair. Thus this project will allow us to validate glycomolecules as potential therapeutic agents for MS using our cultures that mimic the intact CNS environment/damaged CNS prior to using animal models of MS