Table 1

Remyelinating agents recently or currently under investigation

Retinoid X receptor-γ (RXR-γ) agonistsRXR-γ is significantly upregulated in oligodendrocyte-derived cells in remyelinating lesions in experimental lysolecithin (LPC) models and in the CNS in humans. Administration of an RXR-γ agonist (9-cis-retinoic acid) upregulated endogenous OPC differentiation and increased myelination in demyelinated cerebellar slice cultures, suggesting that RXR-γ is a feasible target for CNS remyelinating therapy
Anti-LINGO-1 monoclonal antibodyLINGO-1 is a transmembrane signal-transducing molecule that is expressed on oligodendrocytes and neurons in the CNS, which inhibits oligodendrocyte differentiation, and may be a potentially important cause of remyelination failure in MS. Anti-LINGO-1 monoclonal antibody enhanced oligodendrocyte differentiation and myelination, and promoted functional recovery in EAE models, which correlated with radiological and electron microscopy metrics showing increased remyelination and axonal integrity in the spinal cord
OlexosimeOlexosime, which has a number of potentially neuroprotective and neuroregenerative properties, accelerated maturation of oligodendrocytes and promoted remyelination in vitro and in vivo in LPC and cuprizone mouse models of demyelination
Mesenchymal stem cellsAutologous mesenchymal stem cells are multipotent bone marrow-derived stromal cells that may have potential to promote myelin repair, in addition to other potential complementary effects, in MS. A phase II trial of autologous mesenchymal stem cells in secondary progressive MS patients with visual pathway disease (MSCIMS) demonstrated significant improvement in visual acuity, visual evoked potential latency and optic nerve area
Wnt signalling pathway modifiersThe Wnt signalling pathway, which is an important aetiology in a number of neoplastic conditions, also downregulates differentiation of OPCs. In experimental models, inhibiting the activity of tankyrase (a polymerase enzyme) can reduce activity in the Wnt signalling pathway, enhancing remyelination
Other agentsA number of other therapies may also promote remyelination in experimental models, such as progesterone and fingolimod
  • CNS, central nervous system; EAE, experimental allergic encephalitis; MS, multiple sclerosis; OPC, oligodendrocyte precursor cell.