14/03/2024
A study of existing mathematical models to describe the mechanisms of autoimmune diseases was carried out by our specialists. This work allows us to systematically evaluate existing approaches to the quantitative pharmacology of autoimmune pathologies.
Mathematical modeling is an important tool in modern drug development. Thus, it is the models that make it possible to transform heterogeneous experimental data from numerous sources into a system of quantitative knowledge and use them to accelerate the creation of new medicines. The indispensability of this tool is especially noticeable in therapeutic areas such as autoimmune diseases, with non-trivial pathogenesis and etiology.
Systems pharmacology models can be used to answer numerous questions in drug development, such as target selection, animal-to-human translation, and indirect comparison of the efficacy and safety of different types of therapy. These models represent a cross-section of existing knowledge and data for individual pathologies. The creation of new mathematical models begins with the study of existing works in this area. This is precisely the main purpose of the published review.
Although the systematic search included more than 180 autoimmune diseases, the results found models for only 13 individual pathologies, with models for 2 systemic pathologies (systemic lupus erythematosus and rheumatoid arthritis) and 11 for organ-specific pathologies. Consequently, the mechanisms of more than 150 other autoimmune pathologies, such as psoriasis, scleroderma, Sjögren’s syndrome, are not currently described using mathematical models.
Approximately one third of all models described systemic activation of T-cell immunity, which is not surprising given that autoimmune diseases are characterized by a response to a self-antigen. Most models have examined the T-cell immune response with an emphasis on T helper cells. In turn, despite their key contribution to the pathology of a number of diseases, B cells are modeled only in selected cases, even in autoimmune diseases that are classified as B cell-mediated, such as systemic lupus erythematosus. Surprisingly, that just under a third of the models are not based on experimental data. The use of such models in clinical drug development is very limited and requires significant improvement.
Taken together, in the work emphasize the need to create new systemic pharmacological models for most autoimmune diseases in order to accelerate the development of new therapeutic agents, including for rare diseases, where rational design of clinical programs is especially in demand due to the small number of patients available for participation in clinical trials.
