Multiple sclerosis is a major neurodegenerative disease. It leads to the demyelination of neurons, in turn leading to impairment and weakness in muscle areas. Combatting this factor has been a major focus of many studies. There has been a lot of research focusing on the remyelination of axons. The process of remyelination is interrupted by the inflammatory environment surrounding the neurons. This makes it difficult for recovery because the debris left behind from the demyelination leads to obstacles for not only remyelination but also axonal growth. A possible solution for this would be to create therapies involving drugs that promote remyelination despite the inflammatory environment. As of today, there is no approved remyelination therapy. There is progress being made which can be seen in a study done by Chen et al., who tested the combination of sephin1 and bazedoxifene.
Chen et al. conducted a study on the inflammatory stress response of the CNS. During the inflammatory stress response, oligodendrocytes that are in the process of remyelinating are protected and work more efficiently (Chen et al., 2023). The integrated stress response is triggered by the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α). When phosphorylated, this factor promotes cellular survival and recovery. The sustained phosphorylation of this factor can have an important effect on the stress response of the CNS. Chen et al.’s study focused on the use of sephin1 and bazedoxifene to enhance the rate of remyelination in rats that had expression of IFN-y in the CNS. IFN-y is a cytokine that triggers the integrated stress response and does not allow for oligodendrocyte precursor cells to differentiate. The use of sephin1 enhances the effects of this cytokine. The use of bazedoxifene allows for the oligodendrocyte precursor cells to differentiate and increase remyelination. Rather than using bazedoxifene on its own, using it in addition with sephin1 has positive effects on the myelination of axons and the amount there are. Their study showed that using these drugs in combination with each other accelerates the remyelination process rather than just using them individually (Chen et al., 2023).
Another study done by Nunes et al. (2025) focused on remyelination and its effect on the function of neurons. They focused on demyelination in the visual pathway by using in vivo and neurophysiological approaches. They focused mainly on the process of remyelination. The researchers induced demyelination in the mice by exposing them to curpizone, which causes cell death, followed by treatment with LL-341070, a thyromimetic. They found that administering high doses of LL-341070 led to an increase of remyelination. Mice that had undergone more than 50% oligodendrocyte loss gained back more than double the amount (Nunes et al. 2025). The latencies of neurons in the visual pathway were also heightened. The amount of time it takes for oligodendrocyte loss also plays a factor as the faster the cells die, the harder it is to gain them back. Also, the longer that there are deficits in the oligodendrocyte population, the more difficult it is to restore previous populations (Nunes et al., 2025).
Both these articles discussed the possible solutions in mitigating demyelination. Demyelination is a serious problem that has many causes and affects a large percentage of the population. Chen et al. (2023) provides insight into combination drug therapies that can be used to promote regrowth of myelin. Similarly, Nunes et al. (2025) present research showing a hormone-based drug that proves to promote remyelination and proliferation of oligodendrocytes. The research done by these studies builds on each other, with one showing possible approaches to demyelination in multiple sclerosis, and one showing approaches to induced demyelination. These studies put with each other provide support for the idea that considering combination drug therapies following induced demyelination is important when trying to find a concrete treatment.
References
Chen, Y., Quan, S., Patil, V., Kunjamma, R. B., Tokars, H. M., Leisten, E. D., ... & Popko, B. (2023). Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. Glia, 71(9), 2180-2195.
Della-Flora Nunes, G., Osso, L. A., Haynes, J. A., Conant, L., Thornton, M. A., Stockton, M. E., ... & Hughes, E. G. (2025). Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function. Nature Communications, 16(1), 732.
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