Progress in developing transgenic monkey model for Huntington's disease

• Type of Material: Article
• Authors: Brooke R. Snyder, Jefferson State Community College; Anthony Chan, Emory University
• Language: English
• Date: 2018-03-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, Springer-Verlag GmbH Austria.
• Final Published Version (URL): http://dx.doi.org/10.1007/s00702-017-1803-y
• Title of Journal or Parent Work: Journal of Neural Transmission
• ISSN: 0300-9564
• Volume: 125
• Issue: 3
• Start Page: 401
• End Page: 417
• Grant/Funding Information: 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.; The Transgenic Huntington’s Disease Monkey Resource (THDMR) and this study are supported by a grant awarded by the ORIP/NIH (OD010930) to AWSC.
• Keywords: Clinical Neurology; Life Sciences & Biomedicine; TONICALLY ACTIVE NEURONS; Nonhuman primates; Transgenic animal model; Neurosciences & Neurology; Neurosciences; NEURONAL INTRANUCLEAR INCLUSIONS; KNOCK-IN MICE; Science & Technology; PLURIPOTENT STEM-CELLS; CELLULAR PHENOTYPES; Huntington's disease; INTERNEURONS EXPRESSING CALRETININ; Comparative animal models; BASAL GANGLIA; MOUSE MODELS; STRIATAL INTERNEURONS; CAG-REPEAT LENGTH
• Research Categories: Biology, Neuroscience; Biology, Genetics; Health Sciences, Pharmacology

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.