Revolutionizing Treatment for Immune-Mediated Inflammatory Diseases We spoke to Dr Sara Marsal, MD PhD, coordinator of the DocTIS project, which aims to drastically improve the prognosis of immune-mediated inflammatory diseases (IMIDs) by identifying highly effective combinatorial therapies for these patients. The DOCTIS project (Development of Combinatorial Therapies for ImmuneMediated Inflammatory Diseases) represents a pioneering research initiative aimed at revolutionizing the treatment landscape for immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, psoriasis, ulcerative colitis, systemic lupus erythematosus, psoriatic arthritis, and Crohn’s disease. These conditions, which result from the chronic, inappropriate activation of the immune system, significantly diminish the quality of life for millions and pose a heavy burden on healthcare systems. Despite advances in therapy over the last two decades, many patients continue to see poor results or eventual loss of response, leading to the discontinuation of treatments. Led by a consortium of international experts across clinical, biological, computational, and epidemiological domains, DOCTIS aims to transform treatment approaches in IMIDs by identifying synergistic combinations of existing drugs. By strategically combining
current approved treatments, the project seeks not only to suppress disease activity to the point of remission but also to decrease the necessary dosages, thereby reducing potential toxicity and the likelihood of therapeutic resistance. This strategy intends to enhance the efficacy of treatments, reduce side effects, and prevent resistance. “Our goal is to employ advanced data analysis and systems biology to identify drug combinations that can effectively bring patients into remission,” explains Dr. Sara Marsal, MD PhD, coordinator of the DOCTIS project. The DOCTIS project not only promises to extend the effective lifespan of current therapies but also represents a costeffective strategy that could alleviate the financial strain on healthcare providers. “Our approach could fundamentally alter how we treat IMIDs by shifting the paradigm from single-drug treatments to tailored combinatorial therapies that are precisely matched to a patient’s specific condition,” Dr. Marsal adds, highlighting the project’s potential to set new standards in personalized
medicine. With a robust framework for clinical trials and collaborations across various European and North American institutions, the DOCTIS project is poised to make substantial contributions to the field of immunology and patient care. Central to the DOCTIS project is its use of high-quality human samples from both IMID patients and healthy controls, combined with curated real-world clinical data and diverse sources of high-quality omics data. This comprehensive approach enables the project to employ advanced computational and systems biology methods to discover synergistic drug pairings. These pairings will subsequently be tested in clinical trials, beginning with detailed patient and sample selection processes as outlined in Work Package 3 (WP3). The clinical data gathered is of granular quality, and the samples are stored in the IMID-Biobank at the Vall d’Hebron Research Institute, which has collected samples from over 17,000 IMID patients. The DOCTIS project is a collaborative effort involving ten leading partners from
Map of millions of blood cells analyzed using single cell sequencing technology in DoCTIS. Each dot represents a cell and they are colored according to the main cell lineages (legend). ScRNAseq allows to analyze the expression of all the 20,000 human genes in each cell type.
Image credit: Vall d’Hebron, Insitut de Recerca for DOCTIS Project.
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