Laquinimod Supports Remyelination in Non-Supportive Environments

Cells

Christoph Schmitz¹  Joel Kaye²  Uta Chrzanowski³  Cordian Beyer³  Stella Nyamoya⁴  Markus Kipp⁵  Julia Steinle⁵ 

[1] Nonclinical Development, Rehovot 7670104, Israel;;AyalaPharma, VP Research &Department of Anatomy II, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany;Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany;Institute of Neuroanatomy and JARA-BRAIN, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany;

关键词: multiple sclerosis;    remyelination;    cuprizone;    neurodegeneration;    laquinimod;   

DOI  :  10.3390/cells8111363

来源: DOAJ

【 摘 要 】

Inflammatory demyelination, which is a characteristic of multiple sclerosis lesions, leads to acute functional deficits and, in the long term, to progressive axonal degeneration. While remyelination is believed to protect axons, the endogenous-regenerative processes are often incomplete or even completely fail in many multiple sclerosis patients. Although it is currently unknown why remyelination fails, recurrent demyelination of previously demyelinated white matter areas is one contributing factor. In this study, we investigated whether laquinimod, which has demonstrated protective effects in active multiple sclerosis patients, protects against recurrent demyelination. To address this, male mice were intoxicated with cuprizone for up to eight weeks and treated with either a vehicle solution or laquinimod at the beginning of week 5, where remyelination was ongoing. The brains were harvested and analyzed by immunohistochemistry. At the time-point of laquinimod treatment initiation, oligodendrocyte progenitor cells proliferated and maturated despite ongoing demyelination activity. In the following weeks, myelination recovered in the laquinimod- but not vehicle-treated mice, despite continued cuprizone intoxication. Myelin recovery was paralleled by less severe microgliosis and acute axonal injury. In this study, we were able to demonstrate that laquinimod, which has previously been shown to protect against cuprizone-induced oligodendrocyte degeneration, exerts protective effects during oligodendrocyte progenitor differentiation as well. By this mechanism, laquinimod allows remyelination in non-supportive environments. These results should encourage further clinical studies in progressive multiple sclerosis patients.

【 授权许可】

Unknown