Researchers Identify Drugs That Promote Remyelination in Mice
In a recent publication in Nature, titled “Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo” a team of researchers from Case Western University and Northwestern University screened a library of small molecules to assess their ability to drive the conversion of oligodendrocyte precursor cells (OPCs) into oligodendrocytes. Initially, these experiments were performed solely in cultured OPCs, revealing seven potential drugs that could enhance the production of oligodendrocytes.
Multiple sclerosis (MS) is characterized by both demyelination (damage to the myelin sheath) and a failure to remyelinate (repair the damaged myelin). Whereas both of these processes provide attractive therapeutic targets, currently available therapies all work by targeting the immune system to stop the autoimmune response and prevent further demyelination. More recently, a lot of research focus has shifted to attempt to find treatments that work by promoting repair of the damaged myelin, thus providing recovery from symptoms.
Remyelination is performed by a type of cell known as an oligodendrocyte. Oligodendrocytes mature from OPCs, which are a type of stem cell found in the central nervous system (CNS). While these OPCs can be found in large numbers in people with MS, they fail to convert into oligodendrocytes and so cannot help to repair the damaged myelin. Therefore, finding a way to promote this process is of particular interest for the development of novel therapeutic options for the treatment of MS.
In this study, the researchers tested the potential of the newly identified drugs to enhance the production of oligodendrocytes in a mouse model of MS. In the model used, a toxin (lysolethicin) is used to create demyelination to mimic that seen in MS. Two of the drugs identified, miconazole and clobetasol, were able to promote the repair of damaged myelin in these mice. Indeed, animals that exhibited severe symptoms showed remarkable recovery after the drugs were administered at the peak of the disease process. While both drugs promote remyelination, clobetasol also functions to suppress the immune system.
These results provide evidence to test miconazole and clobetasol as potentially new therapeutic agents to promote the repair of damaged myelin in people with MS.