A new phenotypic screening platform that identifies biologically-relevant targets and lead compounds for the treatment of Parkinson’s disease
Grant Award Details
Grant Type:
Grant Number:
DISC1-10674
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$112,500
Status:
Closed
Progress Reports
Reporting Period:
Year 1
Grant Application Details
Application Title:
A new phenotypic screening platform that identifies biologically-relevant targets and lead compounds for the treatment of Parkinson’s disease
Public Abstract:
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
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.
Statement of Benefit to California:
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.
