Optimizing the Action Potential of Stem Cell-derived Human Cardiomyocytes for Car

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$1,184,308.00
Award Year:
2012
Program:
SBIR
Phase:
Phase II
Contract:
2R44HL104948-02
Award Id:
n/a
Agency Tracking Number:
R44HL104948
Solicitation Year:
2012
Solicitation Topic Code:
NHLBI
Solicitation Number:
PA11-096
Small Business Information
14656 NEO PKY, CLEVELAND, OH, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
41419487
Principal Investigator:
ANDREW BRUENING-WRIGHT
(503) 494-7732
abrueningwright@chantest.com
Business Contact:
ARTHUR BROWN
(216) 332-1665
abrown@chantest.com
Research Institution:
Stub




Abstract
DESCRIPTION (provided by applicant): Stem Cell-derived Human Cardiomyocytes (SC-hCMs) offer great potential for improving the accuracy of pre- clinical cardiac safety testing. We have characterized a population of SC-hCMs and have demonstrated that these cells show sensitive pharmacology that accurately predicts clinical responses. However, due to low assay throughput and limited resources, only 15 reference compounds were tested. We now propose to increase throughput in preclinical electrophysiology (EP) screens by utilizing a higher-throughput automated EP instrument. We will expand our preclinical in vitro testing to 77 compounds that have been carefully selected based on their known torsadogenic and/or QT prolonging effects. Results from SC-hCM-based assays will be referenced against complete (8 concentration, 8 replicate) concentration-curves of the same compounds generated from high-throughput screens of cell lines expressing each of the major cardiac ion channels. A statistics-based model will be created in collaboration with the U.S. Food and Drug Administration and a leading in silico modeling firm, Leadscope. This model will be based on the unique databases we create which, together the development of software dedicated to mining public and proprietary cardiac databases will dramatically increase productivity of pre-clinical cardiac safet screening. The set of services and products that will result from this project have the potential t save millions of dollars annually by reducing attrition of marketed but cardiotoxic drugs, to improve the safety of drugs in development, and to increase efficiency of drug development by allowing companies to focus on the most promising and safe drug candidates. PUBLIC HEALTH RELEVANCE: The recent availabilityof human myocytes derived from stem cells (SC-hCMs) provides an opportunity to develop pre-clinical cardiac safety assays with better predictive value compared to conventional assays. The benefits to public health are: 1) Improved productivity in pre-clinical cardiac safety screening, thereby reducing risk of adverse cardiac events in clinical trials, and 2) Added cost-efficiencies in the pharmaceutical drug development process.

* information listed above is at the time of submission.

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