The road to remyelination in demyelinating diseases: current status and prospects for clinical treatment

Abstract

Within CNS disorders, demyelinating diseases are among the most devastating and cost intensive due to long-term disabilities affecting relatively young patients. Multiple sclerosis, a chronic inflammatory demyelinating disease in which the persistent inhibitory microenvironment of the resident oligodendrocyte precursor cells abrogates regeneration of myelin sheaths, is the most prominent disease in the spectrum of demyelinating diseases. The essential goal is to stimulate creation of new myelin sheaths on the demyelinated axons, leading to restoration of saltatory conduction and resolving functional deficits. The past few decades witnessed significant efforts to understand the cellular interactions at the lesion site with studies suggesting efficient remyelination as a prerequisite for functional repair. Despite its proven efficacy in experimental models, immunosuppression has not had profound clinical consequences in multiple sclerosis, which argued for a paradigm shift in the design of therapeutics aiming to achieve remyelination. For example, targeting oligodendrocytes themselves may drive remyelination in the CNS. This group and others have demonstrated that natural autoreactive antibodies directed at oligodendrocyte progenitors participate in remyelination. Accordingly, the authors developed a recombinant autoreactive natural human IgM antibody with therapeutic potential for remyelination.

Keywords::

• animal models of MS
• antibodies
• CNS injury
• demyelination
• multiple sclerosis
• myelin
• natural autoantibodies
• remyelination
• therapeutic strategies

Acknowledgements

The authors thank L Dacy for editorial assistance.

Financial & competing interests disclosure

The technology for remyelination-promoting antibody rHIgM22 has been licensed to Acorda Therapeutics, Inc. No royalties have accrued to M Rodriguez or Mayo Clinic to date, but both have rights to receive future royalties. 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.