Evidence map›Paper›PMID 36189602›Full record

ArticleJournal of Huntington's disease2022

Brain Alterations in Aged OVT73 Sheep Model of Huntington's Disease: An MRI Based Approach.

Toloo Taghian, Jillian Gallagher, Erin Batcho, Caitlin Pullan, Tim Kuchel, Thomas Denney, Raj Perumal, Shamika Moore, Robb Muirhead, Paul Herde and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Huntington's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 2 countries.

Toloo TaghianHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Jillian GallagherHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Erin BatchoDepartment of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA.
Caitlin PullanSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Tim KuchelSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Thomas DenneyDepartment of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA.
Raj PerumalSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Shamika MooreSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Robb MuirheadSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Paul HerdeSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Daniel JohnsSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Chris ChristouSouth Australian Health and Medical Research Institute, Gillies Plains, SA, Australia.
Amanda TaylorDepartment of Clinical Sciences, Auburn University, Auburn, AL, USA.
Thomas PasslerDepartment of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA.
Sanjana PulaparthiHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Erin HallHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
Sundeep ChandraSana Biotechnology, South San Francisco, CA, USA.
Charles A O'NeillBio Marin Pharmaceutical Inc., San Rafael, CA, USA.
Heather Gray-EdwardsHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
South Australian Health and Medical Research Institute · AUUniversity of Massachusetts Chan Medical School · USAuburn University · USBioMarin (United States) · USSana Biotechnology (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuntington's disease (HD) is a fatal neurodegenerative autosomal dominant disorder with prevalence of 1 : 20000 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

methodsHere 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.

resultsSimilar 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.

conclusionThis 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.

Indexed as

Huntington DiseaseWhite MatterAgedAnimalsBrainFemaleHumansMagnetic Resonance ImagingMutant ProteinsSheepTissue DistributionMutant Proteinsclinical translationdiffusion tensor imagingHuntington’s diseaselarge animal modelmagnetic resonance spectroscopytransgenic OVT73 sheep model of Huntington’s disease

Identifiers

PMID36189602
PMCPMC9837686
OpenAlexW4298147665

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.