Table 2.
Potential remyelinating and neuroprotective therapies in multiple sclerosis.
| Drug | Proposed mechanism | Results | Reference |
|---|---|---|---|
| Anti-ASIC-1 | Blockage of ASIC-1 prevents excessive intracellular accumulation of injurious Na(+) and Ca(2 +) in MS lesions | Clinical studies suggest neuroprotection as measured by brain atrophy during treatment compared with pretreatment. | (105, 106) |
| Anti-LINGO-1 | Function-blocking anti-LINGO-1 antibodies enhance OPC differentiation and myelination | Phase 2 trial in patients with a first episode of optic neuritis showed an improvement on nerve impulse conduction along the affected optic nerve. Phase 2 trial in RRMS is ongoing. | (107, 108) |
| Benztropine | Antagonism of M1/M3 muscarinic acetylcholine receptors with subsequent stimulation of oligodendrocyte differentiation | In experimental models of MS, benztropine induced the differentiation of OPCs, and enhanced remyelination. | (109) |
| Guanabenz | α2 adrenergic receptor agonist. Protects oligodendrocytes by preventing dephosphorylation of eIF2, increasing oligodendrocyte survival and prevention of myelin loss. | Preclinical studies demonstrated improvement of deficits in EAE. Phase I clinical studies are ongoing. | (110, 111) |
| Laquinimod | Modified quinolone derivative; reduces microglia and astrocyte activation; increases neuroprotection and myelin preservation | Clinical studies suggest neuroprotection as measured by brain atrophy in treated versus untreated patients. | (112–117) |
| Miconazole and clobetasol | Activates eIF2, TX/RXR, and cholesterol signaling | Promoted oligodendrocyte differentiation and enhanced remyelination in in vivo models | (118) |
| Olesoxime | Decreases oxidative stress. Promotes oligodendrocyte maturation and myelin synthesis | Accelerated oligodendrocyte maturation and enhanced myelination in vitro and in vivo without affecting oligodendrocyte survival or proliferation. Phase 1 trail in MS patients completed. | (119, 120) |
| Quetiapine fumarate | Stimulates proliferation and maturation of oligodendrocytes, increases neurotrophic factors, and inhibits activated microglia, astrocytes, and T lymphocytes | Remyelinating and neuroprotective properties in EAE | (121, 122) |
| rHIgM22 | rHIgM22 binds to the surface of oligodendrocytes promoting myelin repair | Preclinical studies indicate that it may protect oligodendrocytes and stimulate myelin repair. Phase I study demonstrated acceptable safety profile. | (123–125) |
OPC, oligodendrocyte precursor cells; eIF2, Eukaryotic Initiation Factor 2; CNS, Central Nervous System; LINGO, leucine-rich repeat and immunoglobulin-like domain-containing, Nogo receptor-interacting protein; rHIgM22, recombinant human IgM antibody 22; EAE, experimental autoimmune encephalomyelitis; ASIC-1, acid-sensing (proton gated) ion channel 1.