The Preclinical Testing Core of the IU/JAX ADPMC will establish and validate a preclinical testing strategy with go/no-go decision points that allow critical and unbiased assessments of potential novel therapeutic agents for the treatment of AD. The core will use a tiered screening strategy for assessing candidate compounds with predetermined go/no-go decision points using pharmacokinetics (PK), pharmacodynamic (PD) biomarkers and functional assessments in biologically and pathologically relevant AD mouse models.
The primary screen in the pipeline is evaluation of pharmacokinetics (PK) of the compound of interest. Informed by exposure levels, secondary screening includes pharmacodynamic and biomarker studies similar to clinical endpoints including PET and MRI imaging. Compounds only advance to tertiary screens to assess functional, symptom modifying effects (e.g. cognition), and therapeutic index if compounds demonstrate disease modifying activity in the secondary screen.