Grant Award Details
Demonstrate that our HitFinder™ library can be screened for phenotypic changes in A53T-IPSC-derived dopaminergic neurons and use a secondary handle to identify the targets responsible.
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Grant Application Details
- A new phenotypic screening platform that identifies biologically-relevant targets and lead compounds for the treatment of Parkinson’s disease
Research Objective
Demonstrate that our HitFinder™ library can be screened for phenotypic changes in A53T-IPSC-derived dopaminergic neurons and use a secondary handle to identify the targets responsible.
Impact
This technology combines phenotypic screening and target-ID eliminating the need to bias assays and/or screening libraries permitting application directly in iPSC-derived cells.
Major Proposed Activities
- Prepare screening library including purchase of compounds and addition of chemical handles for target identification
- Screen library for phenotypic changes in iPSC-derived engineered A53T-synuclein dopaminergic neurons: single point followed by dose-response
- Large-scale preparation of compound-target complex in A53T IPSC-DA-neurons under conditions of phenotypic assay and confirm phenotypic change for target-ID.
- Process scaled-up A53T-DA neurons and attach an affinity tag to the compound-target complex. Identify number of targets that reacted with the ligand (selectivity) and the identity of these targets.
This technology has the potential for broad impact on patients. Immediately, compounds and targets identified from this screen can progress into a drug discovery program to identify new treatments for Parkinson’s disease (PD). PD is estimated to affect 36-60,000 Californians. Application of iPSC-derived neurons permits screening in patient-derived cells to determine if therapeutics/targets are relevant in all forms of PD (genetic and sporadic) and eventually expand to other diseases.