CINAPS is a standardized animal model screening contract to support preclinical assessment of neuroprotective agents for Parkinson’s disease. In the initial phase of this contract, compounds considered for screening were suggested by basic and clinical Parkinson’s disease investigators. Read more >>
CINAPS has developed standardized animal model protocols for both toxin and transgenic models of Parkinson’s disease. Standardized protocols for acute MPTP and 6-OHDA can be found under "CINAPS Animal Models" (below). Experimental design strategies for compound efficacy, pharmacokinetic (PK) analysis, compound stability testing and in vitro assay development include the following:
Isradipine pharmacokinetics – gavage delivery protocol (.pdf 127KB)
Isradipine A53T alpha-synuclein transgenic experimental design (pellet administration) (.pdf 417KB)
Pioglitazone A53T alpha-synuclein transgenic experimental design (gavage administration) (.pdf 165KB)
In considering pathogenic mechanisms associated with Parkinson’s disease, the compound advisory committee for CINAPS identified reagents that could potentially target: 1) enhanced alpha-synuclein degradation or increased misfolded protein clearance through enhancement of chaperone expression or stabilization--candidate compounds include rapamycin (sirolimus), celastrol, geldanamycin; 2) reagents that could lead to reduced oxidative stress--candidate compounds include CDP choline, celastrol, melatonin, R-lipoic acid 3) reagents that could reduce excitotoxic cell death--candidate compounds include memantine, isradipine; 4) reagents that reduce neuroinflammation--candidate compounds include melatonin, celastrol, perindopril, pioglitazone; 5) reagents that diminish mitochondrial dysfunction--compounds include mitoQ, an enantiomer of pramipexole, R-lipoic acid, isradipine, dimebon; and 6) reagents that specifically address pathways associated with genetic forms of Parkinson’s disease. Details for each mechanistic pathway identified are provided below:
The National Institute for Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) offer a number of translational research funding opportunities and resources, to facilitate preclinical compound efficacy testing, validation, optimization, and ADMET (absorption, distribution, metabolism, elimination, and toxicity) studies. NINDS through the Office of Translational Research offers translational R21, U01, and U54 Funding Opportunity Announcements (FOAs) that enable both exploratory/discovery projects (R21) as well as cooperative agreement FOAs designed to facilitate the successful advancement of one (U01) or more (U54) therapeutic compounds to IND (Investigational New Drug) filing. For small businesses interested in therapeutic development, NINDS participates in the SBIR/STTR Small Business Grant Program, which supports translational innovations at different stages of the drug development pipeline. The NIH Blueprint Neurotherapeutics program enables the advancement of promising therapeutic compounds through access to a “virtual” pharma setting supported through contract research organizations that offer compound optimization and ADMET capabilities to Blueprint Neurotherapeutics funded researchers. The NIH Common Fund Molecular Libraries program offers investigators access to large-scale small molecule screening facilities to facilitate identification of chemical probes related to genes, cells, and biochemical pathways of interest. The Therapeutics for Rare and Neglected Disease (TRND) program provides an opportunity to partner with and gain access to rare and neglected disease drug development capabilities, expertise and clinical/regulatory resources in a collaborative environment with the goal of moving promising therapeutics into human clinical trials. Resources offering information on assay development, high-throughput screening strategies and toxicology assessments are also available on the NIH Assay Development and High-Throughput Screening and Tox21 Initiative websites, respectively.
Parkinson’s Disease translational research tools have been developed through support of the National Institutes of Health (NIH) and Non-Profit Research Foundations to facilitate pre-clinical drug-discovery research activities. These research tools include: 1) monoclonal antibodies to specific proteins associated with Parkinson’s Disease such as LRRK2, α-synuclein, Pink1, etc. developed through the NIH sponsored NeuroMab Program and through the Michael J. Fox Foundation (MJFF) LRRK2 antibody project; 2) knockout mouse models and mouse ES cells for Park2, Park 7, Pink1, GBA, LRRK2, α-synuclein, etc. are available through the NIH Knockout Mouse Project (KOMP), the International Mouse Consortium, the MJFF Research Models project, and the Jackson Laboratory Parkinson’s Disease Mouse Model Resource; 3) transgenic mouse models for various genes associated with Parkinson’s Disease are available through the MJFF Research Models project and the Jackson Laboratory Parkinson’s Disease Mouse Model Resource; and 4) Parkinson’s Disease related fibroblast and induced pluripotent stem cell (iPSC) lines are available through the NINDS Repository at Coriell.
CINAPS reports and other information related to the CINAPS mission.
Animal models used by CINAPS for testing potential Parkinson's disease therapeutics.
Compound dossiers of potential neuroprotective agents to treat Parkinson's disease.
Innovative clinical studies using compounds identified by CINAPS.
Database of current Parkinson's disease clinical trials.
NINDS PD website containing information for researchers.
Last Modified September 16, 2014