Evidence map›Paper›PMID 31678095›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2019

GDNF-expressing macrophages restore motor functions at a severe late-stage, and produce long-term neuroprotective effects at an early-stage of Parkinson's disease in transgenic Parkin Q311X(A) mice.

Yuling Zhao, Matthew J Haney, Yeon S Jin, Olga Uvarov, Natasha Vinod, Yueh Z Lee, Benjamin Langworthy, Jason P Fine, Myosotys Rodriguez, Nazira El-Hage and 2 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
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  17. Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Yuling ZhaoCenter for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Matthew J HaneyCenter for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yeon S JinEshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Olga UvarovCenter for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Natasha VinodCenter for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yueh Z LeeDepartment of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Benjamin LangworthyDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jason P FineDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Myosotys RodriguezDepartment of Immunology and Nano-medicine, Florida International University, Herbert Wertheim College of Medicine, Miami, FL, 33199, USA.
Nazira El-HageDepartment of Immunology and Nano-medicine, Florida International University, Herbert Wertheim College of Medicine, Miami, FL, 33199, USA.
Alexander V KabanovCenter for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Elena V BatrakovaCenter for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: batrakov@ad.unc.edu.
University of North Carolina at Chapel Hill · USFlorida International University · US

Funding

Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
Cell-based Platform for Gene Delivery to the BrainR01NS102412 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BATRAKOVA, ELENA · 2018 to 2022
$1.7M
Extracellular Vesicles for CNS Delivery of Therapeutic Enzymes to Treat Lysosomal Storage DisordersR01NS112019 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BATRAKOVA, ELENA · 2019 to 2023
$1.5M
Inflammatory Cells for Transport of Therapeutic Polypeptides Across the BBBR01NS057748 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BATRAKOVA, ELENA · 2008 to 2012
$1.5M
NCATS NIH HHS UL1 TR002489NINDS NIH HHS R01 NS057748NINDS NIH HHS R01 NS102412NINDS NIH HHS R01 NS112019
6 · The paper itself

Abstract

There is an unmet medical need in the area of Parkinson's disease (PD) to develop novel therapeutic approaches that can stop and reverse the underlying mechanisms responsible for the neuronal death. We previously demonstrated that systemically administered autologous macrophages transfected ex vivo to produce glial cell line-derived neurotrophic factor (GDNF) readily migrate to the mouse brain with acute toxin-induced neuroinflammation and ameliorate neurodegeneration in PD mouse models. We hypothesized that the high level of cytokines due to inflammatory process attracted GDNF-expressing macrophages and ensured targeted drug delivery to the PD brain. Herein, we validated a therapeutic potential of GDNF-transfected macrophages in a transgenic Parkin Q311X(A) mice with slow progression and mild brain inflammation. Systemic administration of GDNF-macrophages at a severe late stage of the disease leaded to a near complete restoration of motor functions in Parkin Q311X(A) mice and improved brain tissue integrity with healthy neuronal morphology. Furthermore, intravenous injections of GDNF-macrophages at an early stage of disease resulted in potent sustained therapeutic effects in PD mice for more than a year after the treatment. Importantly, multiple lines of evidence for therapeutic efficacy were observed including: diminished neuroinflammation and α-synuclein aggregation, increased survival of dopaminergic neurons, and improved locomotor functions. In summary, GDNF-transfected macrophages represent a promising therapeutic strategy for PD at both late- and early-stages of the disease.

Indexed as

AnimalsBrainDisease ProgressionDopaminergic NeuronsFemaleGlial Cell Line-Derived Neurotrophic FactorHumansMacrophagesMiceMice, TransgenicNeuroprotectionParkinsonian DisordersTime FactorsTransfectionUbiquitin-Protein LigasesGDNF protein, humanGlial Cell Line-Derived Neurotrophic Factorparkin proteinUbiquitin-Protein LigasesGDNFMacrophagesNeuroinflammationParkinson’s diseaseTransgenic mice

Identifiers

PMID31678095
PMCPMC6927551
OpenAlexW2982637385

What OpenQuestion holds

Textmetadata
LicenceTDM
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.