Grant Award Details

A new phenotypic screening platform that identifies biologically-relevant targets and lead compounds for the treatment of Parkinson’s disease
Grant Number: 
DISC1-10674
Project 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.

Investigator: 
Institution: 
Type: 
PI
Disease Focus: 
Neurological Disorders
Parkinson's Disease
Human Stem Cell Use: 
iPS Cell
Award Value: 
$150,000
Status: 
Active

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

  • 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.