title: Laquinimod rescues striatal, cortical and white matter pathology and results in modest behavioural improvements in the YAC128 model of Huntington disease.
abstract: 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.
authors.affiliation: Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia-Miralles
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Xin
authors.initials: X
authors.lastname: Hong
authors.affiliation: Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.
authors.forename: Liang Juin
authors.initials: LJ
authors.lastname: Tan
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Caron
authors.affiliation: Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Xuan Vinh
authors.initials: XV
authors.lastname: To
authors.affiliation: Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.
authors.forename: Rachel Yanping
authors.initials: RY
authors.lastname: Lin
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Franciosi
authors.affiliation: Teva Pharmaceutical Industries Ltd., 5 Basel St., Petach Tikva, 4951033, Israel.
authors.forename: Spyros
authors.initials: S
authors.lastname: Papapetropoulos
authors.affiliation: Teva Pharmaceutical Industries Ltd., 5 Basel St., Petach Tikva, 4951033, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Hayardeny
authors.affiliation: Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.|Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.|Teva Pharmaceutical Industries Ltd., 5 Basel St., Petach Tikva, 4951033, Israel.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Kai-Hsiang
authors.initials: KH
authors.lastname: Chuang
authors.affiliation: Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Pouladi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006816:Huntington Disease / Q000188:drug therapy* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D066127:White Matter / Q000187:drug effects* / Q000473:pathology
chemical_list: D015850:Interleukin-6; D015363:Quinolones; C476223:laquinimod