ArticlePloS one2016
Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson's Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Construct optimization for AAV-mediated human α-syn overexpression, and validation across research settings: Development of a shared tool for the research community.Journal of Parkinson's disease · 2026Article
- Genetically Modified Primate Models for Brain Disorder Research.Neuroscience bulletin · 2026Review
- Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.Journal of medical virology · 2025Review
- Drug discovery and development for Parkinson's disease: are preclinical models good enough?Frontiers in aging neuroscience · 2025Review
- Mitophagy Upregulation Occurs Early in the Neurodegenerative Process Mediated by α-Synuclein.Molecular neurobiology · 2024Article
- An accelerated Parkinson's disease monkey model using AAV-α-synuclein plus poly(ADP-ribose).Cell reports methods · 2024Article
- Nigral ATP13A2 depletion induces Parkinson's disease-related neurodegeneration in a pilot study in non-human primates.NPJ Parkinson's disease · 2024Article
- In vivo bioluminescence imaging of the intracerebral fibroin-controlled AAV-α-synuclein diffusion for monitoring the central nervous system and peripheral expression.Scientific reports · 2024Article
- Genetically modified non-human primate models for research on neurodegenerative diseases.Zoological research · 2024Review
- The AAV-α-Synuclein Model of Parkinson's Disease: An Update.Journal of Parkinson's disease · 2024Review
- Development and characterization of a non-human primate model of disseminated synucleinopathy.Frontiers in neuroanatomy · 2024Article
- Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates.Brain : a journal of neurology · 2023Article
- Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model.Nature communications · 2023Article
- Parkinson's Disease: Exploring Different Animal Model Systems.International journal of molecular sciences · 2023Review
- Characterisation of functional deficits induced by AAV overexpression of alpha-synuclein in rats.Current research in neurobiology · 2023Article
- Visualizing advances in the future of primate neuroscience research.Current research in neurobiology · 2023Review
- Spatially resolved gene regulatory and disease-related vulnerability map of the adult Macaque cortex.Nature communications · 2022Article
- Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson's Disease.Genes · 2022Review
- AnFrontiers in neuroscience · 2022Article
- Adeno-Associated Viral Vectors as Versatile Tools for Parkinson's Research, Both for Disease Modeling Purposes and for Therapeutic Uses.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 1012 gp/ml), this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform.
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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.