Approaches to Demyelination Therapy in MS and PD

    This semester, I had the privilege of hearing Dr. Yanan Chen speak about her research on the role of oligodendrocytes in multiple sclerosis. Her lab focuses on MS as a proxy for studying oligodendrocytes because MS is one of the best-characterized demyelinating disorders among other CNS disorders; thus, they use MS as a consistent model for investigating oligodendrocyte stress and cytoprotective responses to CNS inflammation while also seeking more effective therapies for slowing down or completely halting the progression of MS.

    This is where the work of authors Shihao Cui, Shengyuan Wang, Min Liu, Qian Zou, Zhiyou Cai, and Jingxi Ma becomes relevant. In their paper, “Enhancing oligodendrocytes generation and myelin renewal by vitamin C mitigate Parkinson-relevant phenotypes in a murine model of Parkinson’s disease,” they investigate the therapeutic effects of vitamin C in promoting myelin regeneration via the MPTP mouse model known for presenting key features of Parkinson's pathology. Here, Cui et al. used in vitro oligodendrocyte precursor cell differentiation systems to “confirm that vitamin C enhanced the differentiation of OPC into oligodendrocytes” (Cui et al., 2026) and ameliorated myelin damage while also protecting dopaminergic neurons, which led to significant improvements in PD-relevant symptoms. These observed effects of VC were mediated through the activation of Ten-eleven translocation, or TET, enzymes, which promote DNA hydroxymethylation and subsequent expression of genes essential for oligodendrocyte differentiation.

    However, the pathological pathway of MS differs from PD. In the case of PD, it has only recently been discovered that the damage extends beyond dopaminergic neurons and, in fact, is implicated in glial cell populations. Additionally, the oligodendrocyte damage and therapies for both diseases target different pathways: Dr. Chen’s lab previously found that AA147, a compound activator of the ATF6 signaling arm of the UPR, reduced endoplasmic reticulum stress, oligodendrocyte loss, and demyelination while also successfully suppressing T cells in the CNS without altering the peripheral immune response. In PD, the loss of dopaminergic neurons caused by myelin loss leads to tremors, bradykinesia, and postural instability, and for now, the most common treatment is prescribing dopamine replacement therapy to make up for the loss of dopaminergic neurons. 

    With this in mind, I don’t expect that the benefits of vitamin C on OPC differentiation would replicate the exact same results if used as a therapy for MS, but I am still curious as to how treatments for both MS and PD could overlap now that more research is being done on the implications of glial cells in PD. 

​​Works Cited​ 

Cui, S., Wang, S., Liu, M., Zou, Q., Cai, Z., & Ma, J. (2026). Enhancing oligodendrocytes generation and myelin renewal by vitamin C mitigate Parkinson-relevant phenotypes in a murine model of Parkinson's disease. Frontiers in cellular neuroscience, 20, 1761155. https://doi.org/10.3389/fncel.2026.1761155 

Aksu, M., Kaschke, K., Podojil, J. R., Chiang, M., Steckler, I., Bruce, K., Cogswell, A. C., Schulz, G., Kelly, J. W., Wiseman, R. L., Miller, S. D., Popko, B., & Chen, Y. (2025). AA147 Alleviates Symptoms in a Mouse Model of Multiple Sclerosis by Reducing Oligodendrocyte Loss. Glia, 10.1002/glia.70001. Advance online publication. https://doi.org/10.1002/glia.70001. 

Research. (2026). https://yananchenlab.weebly.com/research.html