Cardiovascular diseases are the number 1 cause of death worldwide, killing more than 18 million people annually. This figure demonstrates that there is still a high unmet medical need for new medicines to treat patients in this therapeutic area. Both academia and the pharmaceutical industry are actively trying to develop novel cardiac drugs. Unfortunately, these are not reaching patients, due to a 91.8% failure rate during clinical development. This data strongly suggest that there is a lack of functionally relevant pre-clinical models of cardiovascular diseases being used during the drug discovery process.
Strides have been made in addressing this issue through the development of cardiovascular engineered heart tissues models using human induced pluripotent (hiPSC)-derived cardiomyocytes and tissue engineering. These models are in the correct species (humans) and have more physiologically relevant read-outs and in this way are more representative of the clinical setting. These 3D cardiac strips are formed by cardiomyocytes and supporting cells compacting around two hanging pillars. Once the cells start contracting, they deflect the pillars and this deflection can be used to quantifiably measure relaxation and contraction, forces and rates of the cardiomyocytes; a readout which has relevance across all cardiovascular diseases.
To efficiently use these models to de-risk failure in clinical trials, they need to be compatible with common workflows in the drug discovery process, such as high throughput screening (HTS) and use of robotics. To enable current 3D cardiac strips to be used in the way the system needs, miniaturisation (reduce cell numbers required and thereby the cost per data point), scalability (large-scale production of the plates used to form the tissues), and automation (compatible with drug discovery robots and/or microfluidic automation) are key aspects. River BioMedics is therefore developing a microtiter plate with a microfluidic layer which is capable of supporting miniaturized versions of the 3D cardiac strip, termed µ3D cardiac strips. These strips can still deliver a physiological readout, but only require 20.000 cells to make, thereby reducing the cost per datapoint sufficiently to make the use of human 3D cardiac strips commercially viable in drug discovery. These plates are designed to be compatible with large-scale production techniques and conform to the standard microtiter plate format. The µ3D cardiac strip technology will be suitable for use in both 1) target-based drug discovery to radically increase compound throughput while maintaining a good level of predictability and 2) phenotypic drug discovery to uncover novel drugs alongside novel pathways and novel targets.
