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Progress in developing transgenic monkey model for Huntington’s disease

  • Translational Neurosciences - Review Article
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Abstract

Huntington’s disease (HD) is a complex neurodegenerative disorder that has no cure. Although treatments can often be given to relieve symptoms, the neuropathology associated with HD cannot be stopped or reversed. HD is characterized by degeneration of the striatum and associated pathways that leads to impairment in motor and cognitive functions as well as psychiatric disturbances. Although cell and rodent models for HD exist, longitudinal study in a transgenic HD nonhuman primate (i.e., rhesus macaque; HD monkeys) shows high similarity in its progression with human patients. Progressive brain atrophy and changes in white matter integrity examined by magnetic resonance imaging are coherent with the decline in cognitive behaviors related to corticostriatal functions and neuropathology. HD monkeys also express higher anxiety and irritability/aggression similar to human HD patients that other model systems have not yet replicated. While a comparative model approach is critical for advancing our understanding of HD pathogenesis, HD monkeys could provide a unique platform for preclinical studies and long-term assessment of translatable outcome measures. This review summarizes the progress in the development of the transgenic HD monkey model and the opportunities for advancing HD preclinical research.

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Acknowledgements

We thank the Yerkes National Primate Research Center (YNPRC) veterinarian staff, primate enrichment team, and animal care personnel for providing superior medical and daily care to HD monkeys as disease progressed. Editorial assistance provided by Ms. Leslee Sinclair. The Transgenic Huntington’s Disease Monkey Resource (THDMR) and this study are supported by a grant awarded by the ORIP/NIH (OD010930) to AWSC. YNPRC is supported by the National Center for Research Resources P51RR165 and is currently supported by the Office of Research and Infrastructure Program (ORIP)/OD P51OD11132.

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  1. Biology Department, Jefferson State Community College, 2601 Carson Road, Birmingham, AL, 35215, USA

    Brooke R. Snyder

  2. Department of Human Genetics, Emory University School of Medicine, Atlanta, USA

    Anthony W. S. Chan

  3. Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Transgenic Huntington’s Disease Monkey Resource, 954 Gatewood Road N.E., Atlanta, GA, 30329, USA

    Anthony W. S. Chan

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Snyder, B.R., Chan, A.W.S. Progress in developing transgenic monkey model for Huntington’s disease. J Neural Transm 125, 401–417 (2018). https://doi.org/10.1007/s00702-017-1803-y

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