Development of an Integrated Platform for the Use of Adult Human Primary Cardiomyocytes in Preclinical Safety Assessment - PROJECT SUMMARY
Current strategies for cardiac safety evaluation of drugs have shown significant limitations. Over the past
5 years, the FDA and pharmaceutical industry leaders have promoted initiatives to develop more predictive
human-relevant preclinical platforms to rectify this problem. In this context, AnaBios established an adult
human primary cardiomyocyte contractility model, which reliably predicts drug-induced pro-arrhythmia risk
with >90% accuracy, as well as contractility risks associated with positive and negative inotropic drugs and
chemotherapeutic agents. Based on such a high predictivity, the International Council for Harmonization (ICH)
of Technical Requirements for Pharmaceuticals for Human Use, recently proposed to incorporate the human
primary cardiomyocyte model in preclinical cardiac safety assessment for regulatory purposes. To address the
anticipated screening needs of the pharmaceutical industry, AnaBios has begun the development of a bright-field
imaging-based platform, MyoBLAZER™, customized towards the specific physiology of the adult human
primary cardiomyocytes; the new platform allows simultaneous contractility measurements of multiple adult
primary cardiomyocytes, significantly increasing throughput compared to commercially available instruments.
The objective of the current SBIR Direct to Phase II grant is to fully develop and optimize the MyoBLAZER™
platform, with respect to bright-field and fluorescence imaging, data analysis, and cell adhesion, in order to
effectively screen large numbers of compounds in the early stages of preclinical drug development. The addition
of fluorescence-based imaging to the MyoBLAZER™ will further enable follow up mechanistic investigations of
drug activity and allow testing of other cell pathways. Moreover, optimization of cell adhesion to the test plates,
will improve the MyoBLAZER™ performance and has a high potential to enhance cell storage and permit the
shipment and distribution of the adult human primary cardiomyocytes for industry-wide utilization. To ensure
the success of the program, AnaBios will combine its expertise in donor organ recovery, cardiomyocyte cell
isolation, bright-field microscopy, cardiac pharmacology and drug discovery, with the world class expertise of
Dr. Daniel Aharoni, an expert in imaging, microscopy, bioengineering and physics, at UCLA and with the
technologies and expertise of Live Cell Technologies LLC, a company led by Harvard’s Dr. Ramaswamy Krishnan,
an expert in biomaterials and in cell-substrate interactions.
