Congenital heart rhythm disorders are rare but potentially life-threatening. For many patients, effective treatments are not yet available. Leiden University Medical Center (LUMC) and biotech company Ncardia have now developed an automated research platform that allows thousands of potential drugs to be tested quickly and in a standardized manner on so-called mini-heart models. The platform – based on stem cell technology – was developed at the Leiden Bio Science Park.
In congenital heart rhythm disorders, the heart's electrical system malfunctions, which can lead to a heart rhythm that is too fast, too slow, or irregular. An estimated one in two thousand people worldwide has this condition. Because these individual conditions are rare, the development of targeted medication lags behind.
Mimicking the human heart
The new platform uses stem cells that are converted into different types of heart cells under laboratory conditions. These cells together form small, three-dimensional structures – so-called micro-tissues – that mimic key aspects of the human heart's function. According to LUMC researcher Richard Davis, these 3D models are considerably more informative than earlier, simpler heart cell models and therefore more suitable for drug research.
However, the increased complexity of the mini-heart models also presents practical challenges, such as reproducibility, cost, and scalability. For this reason, the LUMC sought collaboration with Ncardia, a LUMC spin-off with expertise in automated stem cell-based drug research. Ncardia has fully automated both the production of the mini-heart models and the testing process using robotics and data analysis. This allows thousands of substances to be tested in parallel in a single experiment.
In an initial application, the platform was used for research into CPVT1, a hereditary heart rhythm disorder. More than 2,000 existing drugs were screened. Approximately one hundred of these showed a potentially beneficial effect and are now being further investigated. The results were recently published in the scientific journal Trends in Biotechnology.
The platform can also be used to test the cardiac safety of new drugs and chemicals. Furthermore, the technology offers opportunities for more personalized treatment, for example, by creating mini-heart models from stem cells of individual patients who do not respond to standard therapies.
Funding
The recent collaboration with Ncardia was made possible in part by an Innovation Campus grant from the Province of South Holland and additional funding from the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW).
Bron: ICT&health