Brain Cell Death May Trigger Multiple Sclerosis

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Brain Cell Death May Trigger Multiple Sclerosis
Brain Cell Death May Trigger Multiple Sclerosis

A novel mouse model may provide new clues as to how multiple sclerosis initiates, according to data published in Nature Neuroscience.

A team from the University of Chicago and Northwestern University Feinberg School of Medicine developed the oligodendrocyte ablation Plp1-CreERT;ROSA26-eGFP-DTA (DTA) mouse model in order to examine whether oligodendrocyte death triggers the autoimmune response that attacks myelin.

Approximately 30 weeks after recovering from oligodendrocyte loss and demyelination, the DTA mice developed multiple sclerosis)MS)-like symptoms that were observed in conjunction with extensive myelin and axonal loss, as well as increased numbers of T lymphocytes in the central nervous system and myelin oligodendrocyte glycoprotein (MOG)-specific T cells in lymphoid organs. When those T cells were transferred to naïve mice, the recipients demonstrated neurological defects that correlate with white matter inflammation.

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“To our knowledge, this is the first evidence that oligodendrocyte death can trigger myelin autoimmunity, initiating inflammation and tissue damage in the central nervous system during MS," study author Maria Traka, PhD, of the University of Chicago, said in a statement.

The researchers also used novel nanoparticles to induce immune tolerance to the myelin antigen, which ameliorated symptoms of MS. The nanoparticles, which have been licenced to Cour Pharmaceutical Development Company for development for human trials, performed as well in the model of chronic MS as it did in progressing-remitting models, the authors said.

"It's likely that therapeutic strategies that intervene early in the disease process will have greater impact," study author Stephen Miller, PhD, of Northwestern University Feinberg School of Medicine, said in a statement.

Based on the study results, the authors believe that oligodendrocyte death is a very possible trigger of the autoimmune response seen in MS. This conclusion, however, challenges the prevailing theory that an outside event triggers MS in people who are genetically predisposed. Instead, the authors suggest that an initial brain injury that triggers oligodendrocyte death may result in the development of MS years later.

Reference

Traka M, Podojil JR, Mccarthy DP, Miller SD, Popko B. Oligodendrocyte death results in immune-mediated CNS demyelination. Nat Neurosci. 2015; doi:10.1038/nn.4193.

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