Evidence map›Paper›PMID 25008355›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014

ESCRT-mediated uptake and degradation of brain-targeted α-synuclein single chain antibody attenuates neuronal degeneration in vivo.

Brian Spencer, Sharareh Emadi, Paula Desplats, Simona Eleuteri, Sarah Michael, Kori Kosberg, Jay Shen, Edward Rockenstein, Christina Patrick, Anthony Adame and 3 more

RetractedOpen access · bronzeAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 82 citations in OpenAlex.

  1. Review
  2. Article
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  4. Recombinant Antibody Fragments for Immunotherapy of Parkinson's Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
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  18. Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Brian SpencerNeuroTransit, Inc., San Diego, California, USA.
Sharareh EmadiDepartment of Chemical Engineering, Arizona State University, Tempe, Arizona, USA.
Paula DesplatsDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Simona EleuteriDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Sarah MichaelDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Kori KosbergDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Jay ShenDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Edward RockensteinDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Christina PatrickDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Anthony AdameDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Tania GonzalezDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Michael SierksDepartment of Chemical Engineering, Arizona State University, Tempe, Arizona, USA.
Eliezer MasliahDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA; Department of Pathology, University of California, San Diego, La Jolla, California, USA. Electronic address: emasliah@ucalsd.edu.
University of California, San Diego · USArizona State University · US

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
Tissue Culture CoreP01AG022074 · NIA · J. DAVID GLADSTONE INSTITUTES · PI FINKBEINER, STEVEN M · 2003 to 2012
$27.0M
La Jolla Interdisciplinary Neuroscience Center Cores - Vital VP30NS057096 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI LIPTON, STUART A · 2006 to 2010
$12.7M
B-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2M
a-synuclein clearance strategies for the treatment of Lewy body disease.R37AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2006 to 2014
$2.7M
Clearance Pathways in the CNS in Aging and HIVR01AG043384 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DESPLATS, PAULA ALEJANDRA · 2012 to 2016
$1.9M
NIA NIH HHS AG022074NIA NIH HHS AG18440NIA NIH HHS P01 AG022074NIA NIH HHS P50 AG005131NIA NIH HHS R01 AG018440NIA NIH HHS R01 AG043384NIA NIH HHS R37 AG018440NINDS NIH HHS NS057096NINDS NIH HHS P30 NS057096
6 · The paper itself

Abstract

Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy.

Indexed as

alpha-SynucleinAmino Acid MotifsAnimalsApolipoproteins BAutophagyBehavior, AnimalBrainCell LineEndosomal Sorting Complexes Required for TransportGene OrderGenetic VectorsLentivirusMiceMice, TransgenicNerve DegenerationNerve Tissue Proteinsalpha-SynucleinApolipoproteins BCHMP2B protein, mouseEndosomal Sorting Complexes Required for TransportNerve Tissue ProteinsSingle-Chain Antibodies

Identifiers

PMID25008355
PMCPMC4428402
OpenAlexW2156463301

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.