Evidence map›Paper›PMID 37198883›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023

Tracking human neurologic disease status in mouse brain/plasma using reporter-tagged, EV-associated biomarkers.

Katia E Maalouf, Christine A Vaine, Dawn M Frederick, Akiko Yoshinaga, Wataru Obuchi, Shadi Mahjoum, Lisa Nieland, Jamal Al Ali, D Cristopher Bragg, Xandra O Breakefield and 1 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

6 citing papers in PubMed, 5 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

11 authors at 1 institution in 1 country.

Katia E MaaloufDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Christine A VaineDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Dawn M FrederickDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Akiko YoshinagaDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Wataru ObuchiDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Shadi MahjoumDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Lisa NielandDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Jamal Al AliDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
D Cristopher BraggDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Xandra O BreakefieldDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Collaborative Center for X-linked Dystonia-Parkinsonism, Massachusetts General Hospital, Charlestown, MA 02129, USA; Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA. Electronic address: breakefield@hms.harvard.edu.
Koen BreyneDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA. Electronic address: kbreyne@mgh.harvard.edu.
Harvard University · US

Funding

The power of extracellular vesicles in glioblastomaR35CA232103 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS · 2018 to 2024
$6.9M
NCI NIH HHS R35 CA232103
6 · The paper itself

Abstract

X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease caused by a retrotransposon insertion in intron 32 of the TAF1 gene. This insertion causes mis-splicing of intron 32 (TAF1-32i) and reduced TAF1 levels. TAF1-32i transcript is unique to XDP patient cells and can be detected in their extracellular vesicles (EVs). We engrafted patient and control iPSC-derived neural progenitor cells (hNPCs) into the striatum of mice. To track TAF1-32i transcript spread by EVs, we transduced the brain-implanted hNPCs with a lentiviral construct called ENoMi, which consists of a re-engineered tetraspanin scaffold tagged with bioluminescent and fluorescent reporter proteins under an EF-1α promoter. Alongside this improved detection in ENoMi-hNPCs-derived EVs, their surface allows specific immunocapture purification, thereby facilitating TAF1-32i analysis. Using this ENoMi-labeling method, TAF1-32i was demonstrated in EVs released from XDP hNPCs implanted in mouse brains. Post-implantation of ENoMi-XDP hNPCs, TAF1-32i transcript was retrieved in EVs isolated from mouse brain and blood, and levels increased over time in plasma. We compared and combined our EV isolation technique to analyze XDP-derived TAF1-32i with other techniques, including size exclusion chromatography and Exodisc. Overall, our study demonstrates the successful engraftment of XDP patient-derived hNPCs in mice as a tool for monitoring disease markers with EVs.

Indexed as

Extracellular VesiclesNeurodegenerative DiseasesAnimalsBiomarkersBrainDystonic DisordersGenetic Diseases, X-LinkedHumansMiceTranscription Factor TFIIDBiomarkersTranscription Factor TFIIDbiomarkersbrainExtracellular vesicleshuman iPSC-derived neural progenitor cellsneurologic diseaseTAF1-32ixenograft modelX-linked dystonia-parkinsonism

Identifiers

PMID37198883
PMCPMC10362415
OpenAlexW4376875768

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.