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L8 Laquinimod rescues striatal, cortical and white matter pathology and results in modest behavioural improvements in the YAC128 model of huntington’s disease
  1. Marta Garcia Miralles1,
  2. Xin Hong2,
  3. Nicholas S Caron3,
  4. Liang Juin Tan1,
  5. Yihui Huang1,
  6. Xuan Vinh To2,
  7. Rachel Yanping Lin1,
  8. Sonia Franciosi3,
  9. Spyros Papapetropoulos4,
  10. Liat Hayardeny4,
  11. Michael R Hayden1,3,4,5,
  12. Kai-Hsiang Chuang2,
  13. Mahmoud A Pouladi1,5
  1. 1Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Singapore
  2. 2Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore
  3. 3Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
  4. 4Teva Pharmaceuticals, Netanya, Israel
  5. 5Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Abstract

Background Increasing evidence supports a role for abnormal immune activation and inflammatory responses in Huntington’s disease (HD).

Aim and method 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.

Results 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.

Conclusion Taken together, these results suggest that laquinimod may improve some features of pathology in HD.

  • YAC128
  • Laquinimod

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