Sechenov University has identified promising approaches for treating autoimmune diseases.

The researchers published their findings in the highly-cited international scientific journal Frontiers in Immunology. Autoimmune diseases represent one of the most complex and pressing areas of research today. Type 1 diabetes, systemic lupus erythematosus, and rheumatoid arthritis are just a few examples of diseases that arise from a pathological immune response against healthy tissues in the body.

Despite the social significance of these diseases and the extensive amount of research conducted by scientists, achieving sustained remission with existing medications is not always possible. Developing new pharmaceuticals presents a considerable challenge due to the diversity of autoimmune disorders and numerous "white spots" in understanding the pathophysiology of autoimmunity, which hinder the identification of necessary causal relationships and the formulation of strategies for future research.

A unique tool that significantly enhances the effectiveness of developing new drugs is mathematical modeling. The importance of creating such models has been repeatedly demonstrated by the scientific community and the pharmaceutical industry. Most international pharmaceutical companies actively use mathematical modeling to select the optimal design for clinical trials, expedite the drug development process, and tailor the most effective therapies based on individual patient characteristics. This includes the development of medications for treating autoimmune diseases.

In their work, the staff of the Center for Mathematical Modeling in Drug Development at First Moscow State Medical University, along with their foreign colleagues, conducted a systematic study of all available models of autoimmune diseases to date. The team meticulously analyzed their structure and the underlying hypotheses for alignment with contemporary understandings of the pathophysiology of autoimmunity, as well as evaluated the predictive capability and potential of the models for drug development applications.

“As a result, we concluded that existing models cover only a small number of diseases and consider a very limited range of pathophysiological processes,” said Yaroslav Ugolkov, a junior researcher at the Center for Mathematical Modeling in Drug Development at Sechenov University. “We also found that most innovative therapies and several biological mechanisms are not represented in these models at all. Additionally, many studies provide qualitative rather than quantitative descriptions of biological processes, which limits their application in real clinical trials.”

The systematic search conducted by the research team identified over 180 autoimmune diseases. Ultimately, models were found for 13 individual pathologies, two systemic diseases (systemic lupus erythematosus and rheumatoid arthritis), and 11 organ-specific diseases. The mechanisms of more than 150 autoimmune pathologies, such as psoriasis, scleroderma, Sjögren's syndrome, and many others, are currently not described using mathematical models.

Consequently, the authors of the study concluded that there is a need to develop new models for autoimmune diseases. These models should encompass the most comprehensive set of clinical data, their predictive capabilities must be rigorously validated, and their structure should include mechanisms relevant to new therapeutic targets, such as the interferon-mediated inflammatory pathway or B-cell response.

“Creating such models will accelerate the development of new drugs, including those for rare diseases, where the assistance of mathematical modeling is particularly needed due to the small number of patients,” emphasized Yaroslav Ugolkov.

Currently, the staff at the Center for Mathematical Modeling in Drug Development at Sechenov University is actively working on creating a mathematical platform that thoroughly describes the pathophysiology of autoimmune pathologies for the development of new targeted therapies. For example, a mathematical model of interferon-mediated inflammation in systemic lupus erythematosus has already been created, and a model of B-cell immune behavior in autoimmune pathologies is in development. In addition, researchers are conducting a meta-analysis of clinical trials for scleroderma and myositis for the future development of mechanistic models of these diseases.