A Novel, Robust and Comprehensive Predictive Tool Using Human Disease-Specific Induced Pluripotent Stem Cells for Preclinical Drug Screening
Grant Award Details
Grant Type:
Grant Number:
TRAN4-09884
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Cell Line Generation:
Award Value:
$975,000
Status:
Closed
Progress Reports
Reporting Period:
Final Operational Milestone #3
Grant Application Details
Application Title:
A Novel, Robust and Comprehensive Predictive Tool Using Human Disease-Specific Induced Pluripotent Stem Cells for Preclinical Drug Screening
Public Abstract:
Translational Candidate
A library of induced pluripotent stem cell-derived cardiomyocytes from healthy subjects as well as patients with common hereditary cardiac disorders
Area of Impact
Preclinical toxicity screening and drug discovery
Mechanism of Action
Patients with pre-existing cardiac conditions are more susceptible to drug-induced cardiotoxicity than general population. Including iPSCs derived from this subset of patients along with control iPSC-CMs in an in vitro assay will likely represent the heterogeneity of random population in a clinical trial and will help titrate the threshold for cardiotoxicity in high-risk patients.
Unmet Medical Need
The current preclinical assays are suboptimal and lead to elimination of many potentially promising candidates . Use of this industry-standard patient-specific iPSC-CM library will help accelerate clinical trials by accurate prediction of proarrhythmic liability in high-risk population
Project Objective
Readiness for transfer to manufacturing
Major Proposed Activities
A library of induced pluripotent stem cell-derived cardiomyocytes from healthy subjects as well as patients with common hereditary cardiac disorders
Area of Impact
Preclinical toxicity screening and drug discovery
Mechanism of Action
Patients with pre-existing cardiac conditions are more susceptible to drug-induced cardiotoxicity than general population. Including iPSCs derived from this subset of patients along with control iPSC-CMs in an in vitro assay will likely represent the heterogeneity of random population in a clinical trial and will help titrate the threshold for cardiotoxicity in high-risk patients.
Unmet Medical Need
The current preclinical assays are suboptimal and lead to elimination of many potentially promising candidates . Use of this industry-standard patient-specific iPSC-CM library will help accelerate clinical trials by accurate prediction of proarrhythmic liability in high-risk population
Project Objective
Readiness for transfer to manufacturing
Major Proposed Activities
- Generation of iPSC-CMs from 40 patients with diverse genetic and disease background.
- Detailed molecular and functional characterization of iPSC-CMs using immunofluorescence, patch clamp, calcium imaging, and other tools.
- Validation of iPSC-CMs using a panel of high, intermediate, and low risk proarrhythmic drugs by high throughput multielectrode array (MEA).
Statement of Benefit to California:
California has many pharmaceutical and biotech companies. Currently, a major challenge faced by these companies is the increasing rate of drug withdrawal from market due to unpredictable cardiotoxicity, which is largely due to inefficient screening assays. The proposed predictive tool comprising of human iPSC-CMs from patients with diverse genetic background will revolutionize drug toxicity screening by accurately predicting cardiotoxicity in clinical trials and will reduce the overall cost.