Remyelinating strategies in multiple sclerosis

Abstract

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the CNS characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. In recent years, the importance of the neuronal compartment in the early pathology of multiple sclerosis has become increasingly clear. Direct axonal damage within the early stages of inflammation as well as neuronal injury as a result of chronic demyelination are essential factors for the development of long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has significant implications for treatment, with remyelination of denuded axons to protect neurons from damage being necessary in addition to controlling inflammation. Here, we review recent molecular insights into key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and the regenerative process of remyelination in MS and discuss the resulting options regarding remyelinating treatment strategies.

Keywords::

• drug target
• multiple sclerosis
• myelin repair
• neurodegeneration
• neuroprotection
• oligodendrocytes
• remyelination
• treatment

Financial & competing interests disclosure

F Zipp has received research grants from Teva, Novartis, Merck Serona and Bayer. F Zipp has also received consultation funds from Johnson & Johnson, Novartis, Ono and Octapharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Direct axonal damage within the early stages of inflammation as well as neuronal injury as a result of chronic demyelination are essential factors for the development of long-term disability in multiple sclerosis.

• Remyelination is a spontaneous regenerative process that can occur not only in animal models following experimental demyelination but also in multiple sclerosis patients.

• Spontaneous repair is limited due to an inhibitory microenvironment

• Quantification of remyelination by modern imaging techniques is necessary to evaluate novel treatment strategies.