Format

Send to

Choose Destination
Sci Rep. 2016 Aug 16;6:31652. doi: 10.1038/srep31652.

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

Author information

1
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.
2
Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore.
3
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.
4
Teva Pharmaceutical Industries Ltd., 5 Basel St., Petach Tikva, 4951033, Israel.
5
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.

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.

PMID:
27528441
PMCID:
PMC4985819
DOI:
10.1038/srep31652
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center