Evidence map›Paper›PMID 24525765›Full record

ArticleActa neuropathologica2014

Next-generation active immunization approach for synucleinopathies: implications for Parkinson's disease clinical trials.

Markus Mandler, Elvira Valera, Edward Rockenstein, Harald Weninger, Christina Patrick, Anthony Adame, Radmila Santic, Stefanie Meindl, Benjamin Vigl, Oskar Smrzka and 3 more

Abstract read
In one paragraph

Article in Acta neuropathologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed
14.5field-weighted citation impact, top 1% 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

131 citing papers in PubMed, 220 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Review
  5. Review
  6. Review
  7. Proteolytic therapeutic modalities for amyloidoses: Insights into immunotherapy, PROTAC, and photo-oxygenation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  8. The role of amphipathic and cationic helical peptides in Parkinson's disease.Protein science : a publication of the Protein Society · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Recent Advances in Clinical Trials in Multiple System Atrophy.Current neurology and neuroscience reports · 2024
    Review
  13. Recombinant Antibody Fragments for Immunotherapy of Parkinson's Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  14. Review
  15. Review
  16. Role of neuroinflammation in neurodegeneration development.Signal transduction and targeted therapy · 2023
    Review
  17. Article
  18. Article
  19. Review
  20. Review

71 more citing papers are in PubMed but not listed here.

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

13 authors at 3 institutions in 2 countries.

Markus MandlerAFFiRiS AG, Vienna Biocenter, 1030, Vienna, Austria, markus.mandler@affiris.com.
Elvira Valera
Edward Rockenstein
Harald Weninger
Christina Patrick
Anthony Adame
Radmila Santic
Stefanie Meindl
Benjamin Vigl
Oskar Smrzka
Achim Schneeberger
Frank Mattner
Eliezer Masliah
AFFiRiS (Austria) · ATUniversity of California, San Diego · USVienna Biocenter · AT

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4M
Tissue Culture CoreP01AG022074 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MASLIAH, ELIEZER · 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
Studies on Diagnosis, Pathophysiology, and Treatment of Autonomic Failure in MSAP01NS044233 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOW, PHILLIP A · 2003 to 2014
$12.4M
Mechanisms of Neuroprotection in HIV EncephalitisR01MH062962 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2002 to 2016
$5.2M
B-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2M
Project-002P30NS076411 · NINDS · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · PI LIPTON, STUART A · 2011 to 2016
$4.5M
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
Pathophysiology of DystoniaR13NS047303 · NINDS · EMORY UNIVERSITY · PI DELONG, MAHLON R · 2004 to 2004
$19k
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 AG018440NIMH NIH HHS R01 MH062962NINDS NIH HHS NS044233NINDS NIH HHS NS047303NINDS NIH HHS NS057096NINDS NIH HHS P01 NS044233NINDS NIH HHS P30 NS057096NINDS NIH HHS P30 NS076411
6 · The paper itself

Abstract

Immunotherapeutic approaches are currently in the spotlight for their potential as disease-modifying treatments for neurodegenerative disorders. The discovery that α-synuclein (α-syn) can transmit from cell to cell in a prion-like fashion suggests that immunization might be a viable option for the treatment of synucleinopathies. This possibility has been bolstered by the development of next-generation active vaccination technology with short peptides-AFFITOPEs(®) (AFF)- that do not elicit an α-syn-specific T cell response. This approach allows for the production of long term, sustained, more specific, non-cross reacting antibodies suitable for the treatment of synucleinopathies, such as Parkinson's disease (PD). In this context, we screened a large library of peptides that mimic the C-terminus region of α-syn and discovered a novel set of AFF that identified α-syn oligomers. Next, the peptide that elicited the most specific response against α-syn (AFF 1) was selected for immunizing two different transgenic (tg) mouse models of PD and Dementia with Lewy bodies, the PDGF- and the mThy1-α-syn tg mice. Vaccination with AFF 1 resulted in high antibody titers in CSF and plasma, which crossed into the CNS and recognized α-syn aggregates. Active vaccination with AFF 1 resulted in decreased accumulation of α-syn oligomers in axons and synapses, accompanied by reduced degeneration of TH fibers in the caudo-putamen nucleus and by improvements in motor and memory deficits in both in vivo models. Clearance of α-syn involved activation of microglia and increased anti-inflammatory cytokine expression, further supporting the efficacy of this novel active vaccination approach for synucleinopathies.

Indexed as

alpha-SynucleinAnimalsAntibodiesAxonsCaudate NucleusClinical Trials as TopicDisease Models, AnimalHumansLewy Body DiseaseMemory DisordersMice, Inbred C57BLMice, TransgenicMicrogliaMotor ActivityNerve DegenerationParkinson Diseasealpha-SynucleinAntibodiesSNCA protein, humanSnca protein, mouse

Identifiers

PMID24525765
PMCPMC4034750
OpenAlexW2095442135

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.