Organ-Specific Autoimmune and Rare Diseases: Quantitative Modeling Approaches in Support of the Biology, Disease Progression, Pharmacology, and Developments of Therapies

Autoimmune diseases (AD) feature a number of unique challenges which further manifest themselves in the research and development of novel therapies and effective drugs. Many of these challenges relate directly to the complex etiology of ADs, with a corresponding poor understanding of the actual causes underlying autoimmune reactions. ADs exhibit multi-phase dynamics with involvement of multiple organ systems, often combined with long-term developments into clinical symptoms and difficult-to-predict clinical crises or events. The clinical development of novel treatments against ADs can be further challenged by limited numbers of patients eligible for trials, given the rare – or even ultra rare - disease status for many of these ADs. Given the high interest and multiple unmet medical needs in ADs, we sought to review and exchange on innovative, quantitative, experimental and data analytics methods and approaches which support, accelerate, or streamline the development of novel therapies in organ-specific ADs.

One key goal is to address the need for developing and applying principles of rational drug development in ADs, e.g., addressing translational issues from nonclinical to clinical development of therapies, the identification and validation through quantification of novel biomarkers and clinical endpoints in support of tailored, more personalized treatments and therapy administration / dosing regimens. Towards this goal, we aim at compiling a Research Topic featuring state-of-art examples of various experimental and computational techniques and methodologies, with practical applications in the development of novel AD therapies as well as a discussion relative to current limitations of such approaches (and perspectives on how to overcome these).

For this Research Topic, we welcome submission of articles in the following formats: Brief Research Report, Case Report, Clinical Trial, Conceptual Analysis, General Commentary, Hypothesis and Theory, Methods, Mini Review Opinion, Original Research, Perspective, Reviews and Systematic Reviews that cover, but need not be limited to the following topics:

• Novel experimental nonclinical (in vitro, in vivo) models showing potential for translation into clinical development, in organ-specific ADs such as scleroderma, myositis, inflammatory bowel disease, and idiopathic pulmonary fibrosis;
• Applications of model-informed drug development techniques and methodologies, including but not limited to pharmacometrics and quantitative systems pharmacology (QSP), in support of various aspects pertinent to the development strategy of clinical trials of organ-specific AD treatments;
• Innovations in the design of AD clinical trials, including practical uses of adaptive and model-based designs as well as platform / basket trials with specific focus on rare organ-specific diseases, such as Grave’s disease, sarcoidosis, and vitiligo;
• The search and qualification of novel, informative, predictive biomarkers and clinical endpoints relevant for the treatment of organ-specific ADs, e.g. scleroderma, myositis, inflammatory bowel disease, and idiopathic pulmonary fibrosis;
• The development and applications of ML/AI-based computational methods, in support of network biology and disease progression relevant to ADs and of any of the endeavors listed above.

Please note that Dr Kirill Peskov is affiliated with and and founder of "Modeling & Simulation Decisions FZ-LLC"; Dr Gabriel Helmlinger is a shareholder of Dyne Therapeutics; Dr. Zinnia Parra-Guillen has a part time job as Pharmacometrician at BioInvent International AB and receives research fundings from Roche and Janssen Pharmaceuticals.