Title:Recent Advances on Immunosuppressive Drugs and Remyelination Enhancers for the Treatment of Multiple Sclerosis
Volume: 27
Issue: 30
Author(s): Jennifer Cadenas-Fernández, Pablo Ahumada-Pascual, Luis Sanz Andreu and Ana Velasco*
Affiliation:
- Departamento de Bioquimica y Biologia Molecular, Instituto de Neurociencias de Castilla y Leon (INCYL), Universidad de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Salamanca,Spain
Keywords:
Multiple sclerosis, myelin sheath, remyelination, demyelination, oligodendrocyte, lipid metabolism, immunosuppressive drugs.
Abstract: Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central
nervous system, myelin sheaths consist of lipid structures that are generated from the membrane of oligodendrocytes
(OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In
response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating
lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding
the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability
in young adults in many countries, and its incidence has been increasing in recent decades. Related to its
etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective
treatments for this disease and the immunomodulatory therapies that currently exist have proven limited
success since they only delay the progress of the disease. Nowadays, one of the main goals in MS research is to
find treatments which allow the recovery of neurological disabilities due to demyelination. To this end, different
approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being
considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response
against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in
MS patients and their use may be interesting as potential therapeutic agents in MS disease. To this end, we
compile specific treatments against MS that are currently in the market with remyelination strategies that have
entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic
literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow
down the search results in databases, more specific keywords, such as “myelin sheath”, “remyelination”, “demyelination”,
“oligodendrocyte” and “lipid synthesis” were used to focus the search. We preferred papers published
after January 2015, but did not exclude earlier seminal papers.
