ArticleAnnals of clinical and translational neurology2016
α-synuclein conformational antibodies fused to penetratin are effective in models of Lewy body disease.
Article in Annals of clinical and translational neurology, 2016. 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 It has been retracted, and should not be counted.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 32 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- A bibliometric analysis of alpha-synuclein in Parkinson's disease from 2015 to 2024.Frontiers in neurologyPooled it
- Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial.JAMA neurology · 2018Trial
- Retraction Note: Neuroprotective effects of the Immunomodulatory drug FK506 in a model of HIV1-gp120 neurotoxicity.Journal of neuroinflammation · 2026Article
- RETRACTION: α-Synuclein Conformational Antibodies Fused to Penetratin are Effective in Models of Lewy Body Disease.Annals of clinical and translational neurology · 2026Article
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- ENGINEERED NANOBODIES WITH PROGRAMMABLE TARGET ANTIGEN PROTEOLYSIS (PTAP) FUSIONS REGULATE INTRACELLULAR ALPHA-SYNUCLEIN IN VITRO AND IN VIVO.Research square · 2024Article
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- 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 · 2023Review
- Reduction of αSYN Pathology in a Mouse Model of PD Using a Brain-Penetrating Bispecific Antibody.Pharmaceutics · 2022Article
- Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies.Cellular and molecular life sciences : CMLS · 2022Review
- Applications of nanobodies in brain diseases.Frontiers in immunology · 2022Review
- Therapeutics in the Pipeline TargetingPharmacological reviews · 2022Review
- Transportation of Single-Domain Antibodies through the Blood-Brain Barrier.Biomolecules · 2021Review
- Exploring the Release of Toxic Oligomers from α-Synuclein Fibrils with Antibodies and STED Microscopy.Life (Basel, Switzerland) · 2021Article
- Antibody Fragments as Tools for Elucidating Structure-Toxicity Relationships and for Diagnostic/Therapeutic Targeting of Neurotoxic Amyloid Oligomers.International journal of molecular sciences · 2020Review
- Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases.Pharmaceutics · 2020Review
- Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity.Scientific reports · 2020Article
- Characterization of novel conformation-selective α-synuclein antibodies as potential immunotherapeutic agents for Parkinson's disease.Neurobiology of disease · 2020Article
- α-Synuclein pathology in Parkinson's disease and related α-synucleinopathies.Neuroscience letters · 2019Review
Corrections and comments
- Retraction · 2025-11-30Concerns/Issues about Image · Duplication of/in Image · Investigation by Journal/Publisher · Investigation by Third Party · Unreliable Data · Unreliable Results and/or Conclusions · Upgrade/Update of Prior Notice(s) · · See also: https://pubpeer.com/publications/031CCCA7BB2F970B352E97E43E774B#0
- Correction · 2025-01-27Concerns/Issues about Image · Error in Image · Investigation by Third Party · Updated to Retraction · · See also: https://pubpeer.com/publications/031CCCA7BB2F970B352E97E43E774B#0
- Erratum issued
- Retracted
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveProgressive accumulation of α-synuclein (α-syn) has been associated with Parkinson's disease (PD) and Dementia with Lewy body (DLB). The mechanisms through which α-syn leads to neurodegeneration are not completely clear; however, the formation of various oligomeric species have been proposed to play a role. Antibody therapy has shown effectiveness at reducing α-syn accumulation in the central nervous system (CNS); however, most of these studies have been conducted utilizing antibodies that recognize both monomeric and higher molecular weight α-syn. In this context, the main objective of this study was to investigate the efficacy of immunotherapy with single-chain antibodies (scFVs) against specific conformational forms of α-syn fused to a novel brain penetrating sequence.
methodWe screened various scFVs against α-syn expressed from lentiviral vectors by intracerebral injections in an α-syn tg model. The most effective scFVs were fused to the cell-penetrating peptide penetratin to enhance transport across the blood-brain barrier, and lentiviral vectors were constructed and tested for efficacy following systemic delivery intraperitoneal into α-syn tg mice.
resultTwo scFVs (D5 and 10H) selectively targeted different α-syn oligomers and reduced the accumulation of α-syn and ameliorated functional deficits when delivered late in disease development; however, only one of the antibodies (D5) was also effective when delivered early in disease development. These scFVs were also utilized in an enzyme-linked immunosorbent assay (ELISA) assay to monitor the effects of immunotherapy on α-syn oligomers in brain and plasma.
interpretationThe design and targeting of antibodies for specific species of α-syn oligomers is crucial for therapeutic immunotherapy and might be of relevance for the treatment of Lewy body disease.
Identifiers
What OpenQuestion holds
Registered trials
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.