Parkinson's Disease Research Tools Consortium
Researchers rely on critical tools, such as laboratory reagents and pre-clinical models, to understand the causes and mechanisms underlying disease and to develop effective treatments. When such tools are unavailable, investigators often must make their own, dedicating time and resources that would be better spent studying disease. Many existing tools lack sufficient quality control data, are difficult to obtain by the wider research community, or may come with restrictive license terms and fees that hinder drug-makers' ability to use them. Promoting the generation and availability of critical research tools is a key way to accelerate therapeutic development for Parkinson's patients.
To drive tool development toward the greatest needs of the field, the Foundation is spearheading the Parkinson's Disease Research Tools Consortium. Via this precompetitive consortium, MJFF and industry partners work to better understand existing tools and their use in laboratory experiments, as well as to develop new tools to address unmet challenges.
Industry groups interested in joining the consortium are invited to contact us for more information at firstname.lastname@example.org .
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CONSORTIUMĖSPONSORED TOOLS AND ANIMAL MODELS
Alpha-Synuclein Filament-Specific Antibody
Generation of an alpha-synuclein (aSyn) filament-specific antibody was a project initiated in the first term of the Tools Consortium with Biogen acting as the project co-lead. The protein was generated as an non-Tools Consortium endeavor at Proteos Inc under the guidance of Dr. Poul Henning Jensen at Aarhus University and is available in the Proteins tab of the Tools Catalog. The Tools Consortium-sponsored antibody was generated by Abcam with validation performed by Dr Jensen and is currently available in the Antibodies tab of the Tools Catalog. This antibody is a rabbit monoclonal antibody that recognizes filamentous aSyn in a conformation-specific manner, making it suitable for non-denatured experimental conditions.
Alpha-Synuclein Oligomer-Specific Antibody
Generation of an alpha-synuclein (aSyn) oligomer-specific antibody was a project initiated in the third term of the Tools Consortium with Biogen acting as the project co-lead. The antibody will be generated by Crossbeta Biosciences. More information can be found in the Antibodies tab of the Tools Catalog when viewing the In Development tools.
Alpha-Synuclein Knockdown Viral Vectors
Generation of alpha-synuclein (aSyn) knockdown viral vectors was a project initiated in the second term of the Tools Consortium with Bristol Myers-Squibb as the project co-lead. Three aSyn knockdown viral vectors were generated by GeneDetect Ė a mouse aSyn-specific vector (Mouse SNCA 3xmiR/GFP), a human aSyn-specific vector (Human SNCA 3xmiR/GFP), and a scrambled control vector (Scrambled Control 3xSCRmiR/GFP). More information and a link to access these viral vectors can be found in the Viral Vectors or Alpha-Synuclein tab of the Tools Catalog.
Alpha-Synuclein Aggregation Assay
Generation of an alpha-synuclein (aSyn) aggregation assay was a project initiated in the second term of the Tools Consortium with Pfizer as the project co-lead. The assay is a†high-throughput in vitro†assay designed for screening compounds for inhibition of alpha-synuclein aggregation in a dopamine neuron-like cell line of human origin. This assay was developed by Charles River Discovery (formerly BioFocus) and is available as a fee-for-service assay.†More information and a link to access this assay can be found in the Assay or Alpha-Synuclein tab of the Tools Catalog.
CSF Reference Pools for Alpha-Synuclein Assays
Generation of CSF reference pools for alpha-synuclein (aSyn) assays was a project initiated in the fourth term of the Tools Consortium with Abbvie as the project co-lead in collaboration with the Michael J. Fox Foundation Investigating Synuclein Consortium (ISC). This project involves collection of CSF from Parkinsonís disease patients and measurement of aSyn levels in the CSF samples. CSF will then be pooled into high aSyn and low aSyn groups for use in aSyn assays as reference samples. This project is led by Dr. Brit Mollenhauer at University Medical Center, Goettingen. Storage of the CSF samples will by provided by Dr. Tatiana Foroud at Indiana University. Due to the precious nature of CSF samples, these reference pools will only be available to members of the Research Tools Consortium and members of the ISC.
Alpha-Synuclein KO and Alpha-Synuclein A53T KI Rats
Alpha-synuclein (aSyn) knockout and aSyn A53T knockin rats were generated as a second term project of the Tools Consortium, with Amicus as the project co-lead. Rats were generated by Horizon and are distributed through Horizon. Characterization of the aSyn KO and aSyn A53T KI rats is a fourth term Tools Consortium project, with AstraZeneca as the project co-lead. These rats will be phenotyped across the lifespan to analyze aSyn protein levels and pathology, SNCA mRNA levels, numbers of substantia nigra dopamine neurons, dopaminergic signaling, and behavior, along with other relevent outcome measures. A full description of the characterization plan can be found here. Results of this characterization will be made available once complete.†More information on these rats can be found in the Animal Models or Alpha-Synuclein tab of the Tools Catalog.
GBA D409V KI and GBA D409V KI x Thy-1 aSyn Mice
GBA D409V KI and double mutant GBA D409V KI x Thy-1 alpha-synuclein (aSyn) mice were generated and characterized as a first/second term project of the Tools Consortium, with Amicus as the project co-lead. Mice were generated by Jackson Laboratories, with the GBA D409V KI mice currently distributed through Jackson Laboratories and the GBA D409V KI x Thy-1 aSyn mice to be distributed by Jackson Laboratories once complete. Characterization of GCase levels in these two GBA mouse models was performed by Pfizer and Amicus, with additional characterization by NeuroScience Associates and WIL Research. Results of this characterization will be made available once complete. A second characterization study investigating the impact of the GBA D409V mutation on the aSyn pre-formed fibril model is a fourth term Tools Consortium project, with Merck as the project co-lead. This characterization will be performed by PsychoGenics and NeuroScience Associates. Results of this characterization will be made available once complete. More information on these mice can be found in the Animal Models tab of the Tools Catalog when viewing the Currently Available tools.
Parkin W402A KI Mice
Parkin W402A KI mice were generated as a third term project of the Tools Consortium, with Biogen as the project co-lead. Mice were generated by Taconic and are available through Jackson Laboratories. Validation of this animal model is ongoing with Dr. Matt Goldberg at the University of Alabama and Dr. Howard Fox at the University of Nebraska. More information on the Parkin W402A KI mouse can be found in the Animal Models tab of the Tools Catalog.
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