{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:57:13Z","timestamp":1779364633136,"version":"3.53.0"},"reference-count":88,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JHD"],"published-print":{"date-parts":[[2022,12,16]]},"abstract":"<jats:p>Background: Huntington\u2019s disease (HD) is a fatal neurodegenerative autosomal dominant disorder with prevalence of 1\u200a:\u200a20000 that has no effective treatment to date. Translatability of candidate therapeutics could be enhanced by additional testing in large animal models because of similarities in brain anatomy, size, and immunophysiology. These features enable realistic pre-clinical studies of biodistribution, efficacy, and toxicity. Objective and Methods: Here we non-invasively characterized alterations in brain white matter microstructure, neurochemistry, neurological status, and mutant Huntingtin protein (mHTT) levels in cerebrospinal fluid (CSF) of aged OVT73 HD sheep. Results: Similar to HD patients, CSF mHTT differentiates HD from normal sheep. Our results are indicative of a decline in neurological status, and alterations in brain white matter diffusion and spectroscopy metric that are more severe in aged female HD sheep. Longitudinal analysis of aged female HD sheep suggests that the decline is detectable over the course of a year. In line with reports of HD human studies, white matter alterations in corpus callosum correlates with a decline in gait of HD sheep. Moreover, alterations in the occipital cortex white matter correlates with a decline in clinical rating score. In addition, the marker of energy metabolism in striatum of aged HD sheep, shows a correlation with decline of clinical rating score and eye coordination. Conclusion: This data suggests that OVT73 HD sheep can serve as a pre-manifest large animal model of HD providing a platform for pre-clinical testing of HD therapeutics and non-invasive tracking of the efficacy of the therapy.<\/jats:p>","DOI":"10.3233\/jhd-220526","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T12:38:32Z","timestamp":1664541512000},"page":"391-406","source":"Crossref","is-referenced-by-count":12,"title":["Brain Alterations in Aged OVT73 Sheep Model of Huntington\u2019s Disease: An MRI Based Approach"],"prefix":"10.1177","volume":"11","author":[{"given":"Toloo","family":"Taghian","sequence":"first","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA"},{"name":"Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Batcho","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Pullan","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Kuchel","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Denney","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Perumal","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamika","family":"Moore","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robb","family":"Muirhead","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Herde","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Johns","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Christou","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Gillies Plains, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Passler","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjana","family":"Pulaparthi","sequence":"additional","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Hall","sequence":"additional","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundeep","family":"Chandra","sequence":"additional","affiliation":[{"name":"Sana Biotechnology, South San Francisco, CA, USA"},{"name":"Bio Marin Pharmaceutical Inc., San Rafael, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Bio Marin Pharmaceutical Inc., San Rafael, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Gray-Edwards","sequence":"additional","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA"},{"name":"Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JHD-220526_ref1","first-page":"320","article-title":"On chorea","volume":"26","author":"Huntington","year":"1872","journal-title":"Medical and Surgery Reporter"},{"issue":"2","key":"10.3233\/JHD-220526_ref2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.31887\/DCNS.2007.9.2\/arosenblatt","article-title":"Neuropsychiatry of Huntington\u2019s 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