Abstract
Background
Pelizaeus Merzbacher disease (PMD) is a dysmyelinating disorder of the central nervous system caused by impaired differentiation of oligodendrocytes. This study was prompted by findings that antimuscarinic compounds enhance oligodendrocyte differentiation and remyelination in vitro. One of these compounds, clemastine fumarate, is licensed for treatment of allergic conditions. We tested whether clemastine fumarate can promote myelination in two rodent PMD models, the myelin-deficient and the PLP transgenic rat.
Methods
Pups were treated with daily injections of clemastine (10–30 mg/kg/day) on postnatal days 1–21. Neurologic phenotypes and myelination patterns in the brain, optic nerves, and spinal cords were assessed using histological techniques.
Results
No changes in neurological phenotype or survival were observed even at the highest dose of clemastine. Postmortem staining with Luxol fast blue and myelin basic protein immunohistochemistry revealed no evidence for improved myelination in the CNS of treated rats compared to vehicle-treated littermates. Populations of mature oligodendrocytes were unaffected by the treatment.
Conclusion
These results demonstrate lack of therapeutic effect of clemastine in two rat PMD models. Both models have rapid disease progression consistent with the connatal form of the disease. Further studies are necessary to determine whether clemastine bears a therapeutic potential in milder forms of PMD.
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This project was supported by research funds from the Department of Neurology, University of Wisconsin, Madison
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This project was supported by research funds from the Department of Neurology, University of Wisconsin, Madison
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Turski, C., Turski, G., Chen, B. et al. Clemastine effects in rat models of a myelination disorder. Pediatr Res 83, 1200–1206 (2018). https://doi.org/10.1038/pr.2018.45
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DOI: https://doi.org/10.1038/pr.2018.45
