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The MODEL-AD consortium preclinical testing pipeline: pharmacokinetics and pharmacodynamics of prophylactic treatment with levetiracetam on the 5XFAD mouse model of Alzheimer’s Disease
EP28949
Poster Title: The MODEL-AD consortium preclinical testing pipeline: pharmacokinetics and pharmacodynamics of prophylactic treatment with levetiracetam on the 5XFAD mouse model of Alzheimer’s Disease
Submitted on 14 Aug 2018
Author(s): SJ Sukoff Rizzo1, SK Quinney2, KD Onos1, KJ Keezer1, DR Jones2, AR Masters2, IF Metzger2, JA Meyer2, J Peters2, SC Persohn2, BR McCarthy2, AA Riley2, M Sasner1, G Howell1, H Williams1, AJ Oblak2, BL Lamb2, and PR Territo2
Affiliations: 1The Jackson Laboratory, Bar Harbor, Maine USA; 2Indiana University School of Medicine, Indianapolis, Indiana USA
This poster was presented at AAIC 2018
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Poster Information
Abstract: The preclinical testing core (PTC) of the Model Organism Development for Late Onset Alzheimer’s Disease (MODEL-AD) consortium has established a streamlined preclinical drug testing strategy with go/no-go decision points that allow critical and unbiased assessments of potential therapeutic agents. The goals of the PTC are to develop a testing strategy that maximizes the therapeutic potential of all drug candidates by initiating the dosing strategy prior to the onset of disease relevant biomarker readouts.
The PTC strategy includes a primary screen to determine: 1) drug formulation; 2) drug stability; and 3) in vivo pharmacokinetics and target tissue concentrations in models at disease-relevant ages. A secondary screen evaluates target engagement and disease modifying activity utilizing non-invasive PET/MRI as a pharmacodynamic (PD) readout matched to known disease pathology in the model. Compounds demonstrating positive PD effects in the secondary screen are further interrogated via a tertiary screen of functional assays that assess the compounds ability to normalize a disease-related phenotype in cognition and neurophysiological tests. For the present studies, we selected levetiracetam (LEV), a compound currently in clinical trials for the treatment of cognitive impairment associated with AD, for testing in 5XFAD mice.
Summary: The PTC pipeline for MODEL-AD using levetiracetam as a pipeline testing compound.Report abuse »
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