Evidence map›Paper›PMID 33250718›Full record

ArticleFrontiers in cellular neuroscience2020

Development of Neuroregenerative Gene Therapy to Reverse Glial Scar Tissue Back to Neuron-Enriched Tissue.

Lei Zhang, Zhuofan Lei, Ziyuan Guo, Zifei Pei, Yuchen Chen, Fengyu Zhang, Alice Cai, Gabriel Mok, Grace Lee, Vishal Swaminathan and 3 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cellular neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

46 citing papers in PubMed, 79 citations in OpenAlex.

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  15. In vivo neuroregenerative gene therapy to treat neurodegenerative disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
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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

13 authors at 2 institutions in 2 countries.

Lei ZhangDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Zhuofan LeiDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Ziyuan GuoDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Zifei PeiDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Yuchen ChenDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Fengyu ZhangDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Alice CaiDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Gabriel MokDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Grace LeeDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Vishal SwaminathanDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Fan WangDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Yuting BaiDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Gong ChenDepartment of Biology, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA, United States.
Pennsylvania State University · USJinan University · CN

Funding

GABAergic Synapse Assembly: Extrasynaptic GABAAR TargetingR01MH083911 · NIMH · PENNSYLVANIA STATE UNIVERSITY, THE · PI CHEN, GONG · 2010 to 2014
$1.8M
Converting Alzheimer's reactive astrocytes into functional neuronsR01AG045656 · NIA · PENNSYLVANIA STATE UNIVERSITY, THE · PI CHEN, GONG · 2013 to 2017
$1.6M
NIA NIH HHS R01 AG045656NIMH NIH HHS R01 MH083911
6 · The paper itself

Abstract

Injuries in the central nervous system (CNS) often causes neuronal loss and glial scar formation. We have recently demonstrated NeuroD1-mediated direct conversion of reactive glial cells into functional neurons in adult mouse brains. Here, we further investigate whether such direct glia-to-neuron conversion technology can reverse glial scar back to neural tissue in a severe stab injury model of the mouse cortex. Using an adeno-associated virus (AAV)-based gene therapy approach, we ectopically expressed a single neural transcription factor NeuroD1 in reactive astrocytes in the injured areas. We discovered that the reactive astrocytes were efficiently converted into neurons both before and after glial scar formation, and the remaining astrocytes proliferated to repopulate themselves. The astrocyte-converted neurons were highly functional, capable of firing action potentials and establishing synaptic connections with other neurons. Unexpectedly, the expression of NeuroD1 in reactive astrocytes resulted in a significant reduction of toxic A1 astrocytes, together with a significant decrease of reactive microglia and neuroinflammation. Furthermore, accompanying the regeneration of new neurons and repopulation of new astrocytes, new blood vessels emerged and blood-brain-barrier (BBB) was restored. These results demonstrate an innovative neuroregenerative gene therapy that can directly reverse glial scar back to neural tissue, opening a new avenue for brain repair after injury.

Indexed as

astrocyte-to-neuron conversionblood-brain-barrierbrain injurybrain repairin vivo reprogrammingNeuroD1neuroinflammationneuron to astrocyte ratio

Identifiers

PMID33250718
PMCPMC7674596
OpenAlexW3097059144

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.