Laquinimod rescues striatal, cortical and white matter pathology and results in modest behavioural improvements in the YAC128 model of Huntington disease

• Published in: Scientific reports Vol. 6; no. 1; p. 31652
• Main Authors: Garcia-Miralles, Marta, Hong, Xin, Tan, Liang Juin, Caron, Nicholas S., Huang, Yihui, To, Xuan Vinh, Lin, Rachel Yanping, Franciosi, Sonia, Papapetropoulos, Spyros, Hayardeny, Liat, Hayden, Michael R., Chuang, Kai-Hsiang, Pouladi, Mahmoud A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-08-2016; Nature Publishing Group
• Subjects: 59; 59/57; 631/378/1689; 64/110; 692/617/375; Animals; Atrophy; Behavior, Animal - drug effects; Corpus callosum; Corpus Striatum - drug effects; Corpus Striatum - pathology; Cortex; Diffusion Tensor Imaging; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Humanities and Social Sciences; Huntington Disease - drug therapy; Huntington Disease - physiopathology; Huntington's disease; Huntingtons disease; Immune response; Immunomodulation; Interleukin 6; Interleukin-6 - blood; Magnetic resonance imaging; Male; Mice; Motor task performance; multidisciplinary; Neostriatum; Pathology; Quinolones - pharmacology; Quinolones - therapeutic use; Rodents; Science; Science (multidisciplinary); Substantia alba; White Matter - drug effects; White Matter - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep31652

Increasing evidence supports a role for abnormal immune activation and inflammatory responses in Huntington disease (HD). In this study, we evaluated the therapeutic potential of laquinimod (1 and 10 mg/kg), a novel immunomodulatory agent shown to be protective in a number of neuroinflammatory conditions, in the YAC128 mouse model of HD. Treatment with laquinimod for 6 months rescued atrophy in the striatum, in certain cortical regions, and in the corpus callosum of YAC128 HD mice. Diffusion tensor imaging showed that white matter microstructural abnormalities in the posterior corpus callosum were improved following treatment with low dose (1 mg/kg) laquinimod, and were paralleled by reduced levels of interleukin-6 in the periphery of YAC128 HD mice. Functionally, treatment with laquinimod (1 and 10 mg/kg) led to modest improvements in motor function and in depressive-like behaviour. Taken together, these results suggest that laquinimod may improve some features of pathology in HD, and provides support for the role of immune activation in the pathogenesis of HD.