Evidence map›Paper›PMID 26666562›Full record

ArticleActa neuropathologica communications2015

Cyclosporin promotes neurorestoration and cell replacement therapy in pre-clinical models of Parkinson's disease.

Anna Tamburrino, Madeline J Churchill, Oi W Wan, Yolanda Colino-Sanguino, Rossana Ippolito, Sofie Bergstrand, Daniel A Wolf, Niculin J Herz, Michelle D Sconce, Anders Björklund and 2 more

Open access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 34% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Amyloid-beta glycation induces neuronal mitochondrial dysfunction and Alzheimer's pathogenesis via VDAC1-dependent mtDNA efflux.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. A Mouse Model to Test Novel Therapeutics for Parkinson's Disease: an Update on the Thy1-aSyn ("line 61") Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  10. Article
  11. Repurposing Pomalidomide as a Neuroprotective Drug: Efficacy in an Alpha-Synuclein-Based Model of Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Article
  12. Article
  13. Article
  14. The Molecular Basis of the Interaction of Cyclophilin A with α-Synuclein.Angewandte Chemie (International ed. in English) · 2020
    Article
  15. Article
  16. Microbiome changes: an indicator of Parkinson's disease?Translational neurodegeneration · 2019
    Review
  17. Review
  18. Executive functions in sarcoidosis: a neurocognitive assessment study.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2018
    Article
  19. Article
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

12 authors at 4 institutions in 3 countries.

Anna TamburrinoTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
Madeline J ChurchillVeterans Hospital/Research Services/Portland and Department of Behavioral Neuroscience Oregon Health &, Science University, Portland, OR, USA.
Oi W WanWallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Yolanda Colino-SanguinoWallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Rossana IppolitoTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
Sofie BergstrandTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
Daniel A WolfWallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Niculin J HerzBaylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Houston, USA.
Michelle D SconceVeterans Hospital/Research Services/Portland and Department of Behavioral Neuroscience Oregon Health &, Science University, Portland, OR, USA.
Anders BjörklundWallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Charles K MeshulVeterans Hospital/Research Services/Portland and Department of Behavioral Neuroscience Oregon Health &, Science University, Portland, OR, USA.
Mickael DecressacTelethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy. m.decressac@tigem.it.
Lund University · SETelethon Institute Of Genetics And Medicine · ITOregon Health & Science University · USNeurological Research Institute · US

Funding

Role of the subthalamic nucleus and TrkB following dopamine lossI01BX000552 · VA · PORTLAND VA MEDICAL CENTER · PI MESHUL, CHARLES KENNETH · 2011 to 2018
–
BLRD VA I01 BX000552Telethon TGM11S01
6 · The paper itself

Abstract

backgroundThe early clinical trials using fetal ventral mesencephalic (VM) allografts in Parkinson's disease (PD) patients have shown efficacy (albeit not in all cases) and have paved the way for further development of cell replacement therapy strategies in PD. The preclinical work that led to these clinical trials used allografts of fetal VM tissue placed into 6-OHDA lesioned rats, while the patients received similar allografts under cover of immunosuppression in an α-synuclein disease state. Thus developing models that more faithfully replicate the clinical scenario would be a useful tool for the translation of such cell-based therapies to the clinic.

resultsHere, we show that while providing functional recovery, transplantation of fetal dopamine neurons into the AAV-α-synuclein rat model of PD resulted in smaller-sized grafts as compared to similar grafts placed into the 6-OHDA-lesioned striatum. Additionally, we found that cyclosporin treatment was able to promote the survival of the transplanted cells in this allografted state and surprisingly also provided therapeutic benefit in sham-operated animals. We demonstrated that delayed cyclosporin treatment afforded neurorestoration in three complementary models of PD including the Thy1-α-synuclein transgenic mouse, a novel AAV-α-synuclein mouse model, and the MPTP mouse model. We then explored the mechanisms for this benefit of cyclosporin and found it was mediated by both cell-autonomous mechanisms and non-cell autonomous mechanisms.

conclusionThis study provides compelling evidence in favor for the use of immunosuppression in all grafted PD patients receiving cell replacement therapy, regardless of the immunological mismatch between donor and host cells, and also suggests that cyclosporine treatment itself may act as a disease-modifying therapy in all PD patients.

Indexed as

Disease Models, Animalalpha-SynucleinAnimalsCells, CulturedCell TransplantationCognition DisordersCyclosporineDopamine Plasma Membrane Transport ProteinsEnzyme InhibitorsFemaleHumansMesencephalonMiceMice, Inbred C57BLMice, TransgenicMotor Activityalpha-SynucleinCyclosporineDopamine Plasma Membrane Transport ProteinsEnzyme InhibitorsNerve Tissue ProteinsOxidopamineTyrosine 3-Monooxygenase

Identifiers

PMID26666562
PMCPMC4678733
OpenAlexW2218649651

What OpenQuestion holds

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Registered trials

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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.