MIPT: i-Cardio Way of testing drugs for cardiotoxicity

2024: Presentation of the i-Cardio method

MIPT scientists have developed a way to test drugs for cardiotoxicity using neural networks. The university announced this on September 19, 2024.

The method makes it possible to identify deliberately cardiotoxic substances at the stage of preclinical studies. The system developed by the staff of the Experimental and Cell Medicine Laboratory of MIPT was called i-CARDIO. 

The proposed protocol for testing drugs for cardiotoxicity consists of 4 stages. The first is the isolation of stem cells from a blood sample and their introduction into the germinal state. These stem cells are then differentiated into cardiomyocytes (heart cells) and maintained viable. Next, the test substance is added to them in different concentrations and the cells are stimulated with an electric pulse. At the final stage, the optical mapping method (using computer vision and neural networks) detects the excitation wave with the help of a potential-dependent dye, and the pat-clamp method (stimulation of cells with an electric pulse, where currents from cells are obtained in response) records changes in the currents of ion channels. Based on the data obtained, the researcher draws conclusions about the likelihood of certain outcomes: cell death, arrhythmia, fibrillation, etc.

In the protocol, concentration ranges or signal recording parameters may vary depending on the properties of the substance, but the general algorithm is the same. The research group of the Laboratory of Experimental and Cellular Medicine of MIPT released several scientific works, which demonstrated the proposed method of testing substances for cardiotoxicity and presented the results of testing some substances, including, in particular, a mixture of botulinotoxin with novohytosol, "said Vitaly Dzhabrailov, engineer of the laboratory of experimental and cellular medicine of MIPT.

source = MIPT

Cardiotoxicity is the ability of a drug to influence the occurrence and development of arrhythmia and other heart pathologies. Preclinical trials were conducted in animal models and then clinical trials in humans. However, the nature of animals and human heart cells are not equivalent to each other. That is why testing the drug is unsafe for people. According to Sandaara Kovalenko, a junior researcher at the Laboratory of Experimental and Cell Medicine at the Moscow Institute of Physics and Technology, up to 20 drugs are excluded from the list of drugs allowed for clinical use in Russia due to cardiotoxicity. Therefore, an extremely important stage in the development of testing was the transition from animals to human cells already at the stage of preclinical tests. 

The proposed method (i-CARDIO technology) allows the detection of known cardiotoxic substances before the start of clinical trials. Initially, we conducted an experiment in the culture of human cardiomyocytes using patch clamps (for recording single cell currents) and optical mapping (for recording the conduct of the excitation wave on the cell monolayer). Further, having received a sufficient experimental base, they developed a method by using computer vision and neural networks to predict conduction in the heart tissue under the influence of the substance under study, "continued Sandaara Kovalenko, Candidate of Physical and Mathematical Sciences, Junior Researcher, Laboratory of Experimental and Cellular Medicine, MIPT.

source = MIPT

Several drugs have already been tested for cardiotoxicity: cyclophosphamide (an antitumor drug), erythromycin (an antibiotic for the treatment of bacterial infections), as well as a mixture of botulinum toxin and novochitosol. The latter drug can be used in the future for the treatment of postoperative arrhythmias. 

By the end of 2024, the research team of the Experimental and Cell Medicine Laboratory of MIPT plans to undergo the patenting procedure of the i-CARDIO method.