Evidence map›Paper›PMID 27273432›Full record

ArticleNature communications2016

Human glia can both induce and rescue aspects of disease phenotype in Huntington disease.

Abdellatif Benraiss, Su Wang, Stephanie Herrlinger, Xiaojie Li, Devin Chandler-Militello, Joseph Mauceri, Hayley B Burm, Michael Toner, Mikhail Osipovitch, Qiwu Jim Xu and 10 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04381468 (SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease), which is not on this map. Cited by 121 papers.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed
10.7field-weighted citation impact, top 1% 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.

NCT04381468 phase1 / phase2completednot on this mapstarted 2021, after this paper: background citation

SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer's Disease (AD): A Multi-center, Randomized, Double-Blind, Placebo-Controlled Safety and Biomarker Study of Pepinemab Anti-SEMA4D Antibody in Early-AD

TypeinterventionalSponsorVaccinex Inc.Ran2021 to 2024Enrolled50ConditionsAlzheimer DiseaseArmsPepinemab, Placebo
3 · Its place in the literature

Who cites it

121 citing papers in PubMed, 199 citations in OpenAlex.

  1. Review
  2. Article
  3. Psychosis in Huntington disease: a short update.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
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  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

61 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 2 countries.

Abdellatif BenraissCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Su WangCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Stephanie HerrlingerCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Xiaojie LiCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Devin Chandler-MilitelloCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Joseph MauceriCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Hayley B BurmCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Michael TonerCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Mikhail OsipovitchCenter for Basic and Translational Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark.
Qiwu Jim XuCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Fengfei DingCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Fushun WangCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Ning KangCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Jian KangDepartment of Anatomy and Cell Biology, New York Medical College, Valhalla, New York 10595, USA.
Paul C CurtinPsychogenics, Inc., Tarrytown, New York 10591, USA.
Daniela BrunnerPsychogenics, Inc., Tarrytown, New York 10591, USA.
Martha S WindremCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Ignacio Munoz-SanjuanCHDI Foundation and CHDI Management, Inc., 6080 Center Drive, Suite 100, Los Angeles, California 90045, USA.
Maiken NedergaardCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Steven A GoldmanCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
University of Rochester Medical Center · USPsychogenics (United States) · USUniversity of Copenhagen · DKCHDI Foundation · USNew York Medical College · USRigshospitalet · DK

Funding

Para-Vascular Basis of Small Vessel DiseaseR01NS100366 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2016 to 2020
$3.8M
A Humanized Mouse Model of Astrocytic Pathology in SchizophreniaR01MH099578 · NIMH · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN, NEDERGAARD, MAIKEN · 2013 to 2017
$2.8M
An iPSC based humanized mouse model of dysmyelination in schizophreniaR01MH104701 · NIMH · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN · 2014 to 2018
$2.1M
Failure of metabolite clearance in a model of multi-lacunar infarctsR01NS078167 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2012 to 2016
$1.8M
The glymphatic system, a new concept in glia biologyR01NS078304 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2012 to 2016
$1.7M
Molecular Regulation of Human Glial Progenitor Cell-Based RemyelinationR01NS075345 · NINDS · UNIVERSITY OF ROCHESTER · PI GOLDMAN, STEVEN ALAN · 2011 to 2015
$1.7M
ATP as the instigator of inflammatory responses to spinal cord injuryR01NS075177 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2012 to 2016
$1.6M
Glymphatic function in a transgenic rat model of Alzheimer's diseaseR01AG048769 · NIA · UNIVERSITY OF ROCHESTER · PI BENVENISTE, HELENE D, NEDERGAARD, MAIKEN · 2014 to 2018
$1.4M
NIA NIH HHS R01 AG048769NIMH NIH HHS R01 MH099578NIMH NIH HHS R01 MH104701NINDS NIH HHS R01 NS075177NINDS NIH HHS R01 NS075345NINDS NIH HHS R01 NS078167NINDS NIH HHS R01 NS078304NINDS NIH HHS R01 NS100366
6 · The paper itself

Abstract

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder.

Indexed as

AnimalsBehavior, AnimalChimeraCognitionCrosses, GeneticDisease ProgressionFemaleHuman Embryonic Stem CellsHumansHuntingtin ProteinHuntington DiseaseHyaluronan ReceptorsMaleMiceMotor ActivityNeostriatumHtt protein, mouseHuntingtin ProteinHyaluronan Receptors

Identifiers

PMID27273432
PMCPMC4899632
OpenAlexW2411185224

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.