Evidence map›Paper›PMID 25369767›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015

Enhanced efficacy of the CDNF/MANF family by combined intranigral overexpression in the 6-OHDA rat model of Parkinson's disease.

Óscar Cordero-Llana, Benjamin C Houghton, Federica Rinaldi, Hannah Taylor, Rafael J Yáñez-Muñoz, James B Uney, Liang-Fong Wong, Maeve A Caldwell

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Hydrogel-based neural engineering for skin wound healing.Frontiers in cell and developmental biology · 2026
    Review
  4. Recent developments in gene therapy for Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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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

8 authors at 2 institutions in 1 country.

Óscar Cordero-LlanaSchool of Clinical Sciences, Medical Sciences Building, University Walk, Bristol, UK.
Benjamin C HoughtonSchool of Clinical Sciences, Medical Sciences Building, University Walk, Bristol, UK.
Federica RinaldiSchool of Clinical Sciences, Medical Sciences Building, University Walk, Bristol, UK.
Hannah TaylorSchool of Clinical Sciences, Medical Sciences Building, University Walk, Bristol, UK.
Rafael J Yáñez-MuñozSchool of Biological Sciences, Royal Holloway, University of London, Egham, UK.
James B Uney1] School of Clinical Sciences, Medical Sciences Building, University Walk, Bristol, UK [2] Regenerative Medicine Laboratory, Medical Sciences Building, University Walk, Bristol, UK.
Liang-Fong Wong1] School of Clinical Sciences, Medical Sciences Building, University Walk, Bristol, UK [2] Regenerative Medicine Laboratory, Medical Sciences Building, University Walk, Bristol, UK.
Maeve A Caldwell1] School of Clinical Sciences, Medical Sciences Building, University Walk, Bristol, UK [2] Regenerative Medicine Laboratory, Medical Sciences Building, University Walk, Bristol, UK.
University of Bristol · GBRoyal Holloway University of London · GB

Funding

Medical Research Council MC_G0901331Medical Research Council MC_PC_09002Parkinson's UK G-0915Parkinson's UK K-1104
6 · The paper itself

Abstract

Cerebral Dopamine Neurotrophic Factor (CDNF) and Mesencephalic Astrocyte-derived Neurotrophic factor (MANF) are members of a recently discovered family of neurotrophic factors (NTFs). Here, we used intranigral or intrastriatal lentiviral vector-mediated expression to evaluate their efficacy at protecting dopaminergic function in the 6-OHDA model of Parkinson's disease (PD). In contrast to the well-studied Glial-Derived Neurotrophic Factor (GDNF), no beneficial effects were demonstrated by striatal overexpression of either protein. Interestingly, nigral overexpression of CDNF decreased amphetamine-induced rotations and increased tyroxine hydroxylase (TH) striatal fiber density but had no effect on numbers of TH(+) cells in the SN. Nigral MANF overexpression had no effect on amphetamine-induced rotations or TH striatal fiber density but resulted in a significant preservation of TH(+) cells. Combined nigral overexpression of both factors led to a robust reduction in amphetamine-induced rotations, greater increase in striatal TH-fiber density and significant protection of TH(+) cells in the SN. We conclude that nigral CDNF and MANF delivery is more efficacious than striatal delivery. This is also the first study to demonstrate that combined NTF can have synergistic effects that result in enhanced neuroprotection, suggesting that multiple NTF delivery may be more efficacious for the treatment of PD than the single NTF approaches attempted so far.

Indexed as

Gene ExpressionAnimalsBehavior, AnimalCell LineDisease Models, AnimalGene OrderGenetic VectorsHumansImmunohistochemistryLentivirusNerve Growth FactorsNeuronsOxidopamineParkinson DiseaseRatsRecombinant Fusion ProteinsCDNF protein, ratMANF protein, ratNerve Growth FactorsOxidopamineRecombinant Fusion ProteinsTyrosine 3-Monooxygenase

Identifiers

PMID25369767
PMCPMC4445614
OpenAlexW2093248461

What OpenQuestion holds

Textmetadata
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.