On the way to a personalized prognosis of side effects

Researchers at the University of California at San Diego have developed a model that can be used to predict the side effects of the drug when it is used by different patients. 

The head of the study, Professor Bernhard Palsson, notes that the side effects are very individual and taking the same drug can cause different reactions in different people. Therefore, a tool that allows you to predict the side effects of drugs is potentially able to increase the efficiency of pharmaceutical companies. Having such a tool at their disposal, they could divide patients into groups before the start of clinical trials, depending on the predisposition to the development of certain side effects.

The authors chose human erythrocytes as the object of the study, since these cells are easily isolated from whole blood samples and represent a very simple platform for identifying biomarkers associated with side effects of drugs.

Based on genomic and metabolomic data obtained by analyzing the cells of 24 people, the researchers created a personalized prognostic model for each of them. These models were used to understand at the metabolic level why some people develop side effects on the drug ribavirin, used to treat hepatitis C, while others do not cause adverse reactions. The most serious side effect of ribavirin is anemia developing in 8-10% of patients taking it, a condition characterized by a marked decrease in the number of red blood cells in the blood.

Subsequently, the authors used the developed model to identify patients at risk for this side effect, as well as genetic variation (inosine triphosphatase deficiency), potentially protecting against its development.

Diagram from an article in Cell SystemsThey note that today the model is at the stage of proof of concept.

However, the results obtained indicate the feasibility of using personalized kinetic models to predict the side effects of drugs. They also emphasize that to confirm the predictive power of the model, it is necessary to repeat the study with at least several hundred people.

In the near future, they plan to develop similar predictive models for platelets, which are a much more complex object compared to erythrocytes. The ultimate goal is to create a model for liver cells – hepatocytes, since the vast majority of drugs are metabolized in the liver and it is the place of manifestation of many side effects.

Article by Aarash Bordbar et al. Personalized Whole-Cell Kinetic Models of Metabolism for Discovery in Genomics and Pharmacodynamics is published in the journal Cell Systems.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru according to the University of California, San Diego: Researchers are on their way to predicting what side effects you'll experience from a drug.