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
public, private, and non-profit sectors, each bringing unique expertise to tackle immunemediated inflammatory diseases (IMIDs). Among these, the Vall d’Hebron Research Institute (VHIR) in Catalonia stands out for its expansive research from basic science to clinical trials. The National Center for Genomic Analysis (CNAG-CRG) in Spain is also included in this project. It is known for its leading-edge genomic sequencing capabilities. Cardiff University contributes with its advanced medical education and research programs, enhancing the health and wealth of populations globally.
The Consorci Institut D’Investigacions Biomediques August Pi Sunyer (IDIBAPs, Spain) integrates basic and clinical research, aiming for groundbreaking advancements in biomedicine. The University of Verona (Italy) brings its extensive expertise in dermatology and Charité – Universitätsmedizin Berlin (Germany) is a top-tier medical research center in gastroenterology. Across the Atlantic, the non-profit organization HudsonAlpha Institute furthers the project with its commitment to genomic medicine and scientific discoveries in health. The biotechnology company IMIDomics specialized in drug discovery and precision
medicine for IMIDs, is a key factor that is fostering the translation of the findings of the project into the healthcare sector. Finally, Zabala enhances the project with specialized consultancy in R&D and innovation management, ensuring efficient technology transfer and project execution. Together, these partners form a powerful consortium equipped to make significant advancements in the treatment of IMIDs.
where systems biology methods are used to integrate this detailed data to identify the most complementary pairs of drugs for single-cell analysis, which are revolutionary in biotechnology. These methods allow us to examine each cell individually, providing a deeper understanding of biology and enabling us to tailor treatments more effectively,” explains Antonio Julià, Chief Data Scientist at IMIDomics.
“Our goal is to employ advanced data analysis and systems biology to identify drug combinations that can effectively bring patients into remission”
Advancing Genomic and Single-Cell Technologies
Among other advanced methods, the researchers in DoCTIS are using established bulk transcriptomes omic as well as cutting-edge single-cell technologies to analyze vast datasets from IMID patients. These methods allow an unprecedented characterization of the biological processes and cellular dynamics occurring in inflammatory diseases. This dual approach is critical in Work Package 5,
Transitioning into The Critical Phase of Preclinical Validation and Clinical Trials
Building on the technological and clinical advancements, the DOCTIS project is now transitioning into the critical phase of preclinical validation and clinical trials as part of Work Package 8 (WP8). This stage is essential to provide a proof of concept of the strategy used to identify combination therapies is powerful but, mostly, to provide a new and better way to treat IMID patients.
The clinical trial is designed to validate the effectiveness of the drug combinations in achieving remission. Also, while the drugs that are being combined are secure and have been used safely in many millions of patients, it is important to evaluate the presence of side effects. The outcomes of these trials have the potential to significantly alter treatment protocols for IMIDs, shifting from a one-size-fits-all approach to a more individualized approach.
Impact on Healthcare, Policies, and Regulatory Changes
The introduction of DOCTIS’s combinatorial therapies is projected to significantly lower healthcare costs. This therapeutic strategy is designed to be more effective, have fewer side effects, and reduce treatment failures, thereby alleviating the financial strain on healthcare systems.
The results of the DOCTIS project may also lead to changes in healthcare policies. This would ensure that new and effective treatments reach patients faster and without bureaucratic delays.
The techniques developed through the DOCTIS project hold promise for application to other chronic conditions. By applying the project’s methodologies to other common diseases, there’s potential to spark a wave of new research and innovative treatments across various medical fields.
DOCTIS also emphasizes the importance of a multidisciplinary approach in medical education. Future training programs might integrate genetics, systems biology, and personalized medicine more deeply, equipping new healthcare professionals with the skills needed to implement these advanced treatment strategies.
Over the next two years, DOCTIS plans to expand its research and forge new partnerships, aiming to reinforce its impact on medical research and patient care. This long-term vision underscores the project’s commitment to pioneering new standards in healthcare, redefining how diseases are treated and managed globally. DOCTIS is not only transforming the treatment landscape for IMIDs, but also demonstrating what’s possible in modern medicine.
DocTIS
Decision on optimal combinatorial Therapies in IMIDS using Systems Approaches
Project Objectives
DOCTIS utilizes good-quality human samples from IMID patients and healthy controls, curated real-world clinical data, different sources of high-quality omics data, state of the art animal model testing, and advanced computational and systems biology to discover synergistic drug pairings to be tested in an innovative clinical trial.
Project Funding
The DoCTIS project has received funding from the European Union’s H2020 research and innovation program under grant agreement 848028.
Project Consortium
Coordinator:
• Vall d’Hebron Institut de Recerca (VHIR) Partners:
• Centro Nacional de Análisis Genómico (CNAG-CRG) • Cardiff University • Consorci Institut D’Investigacions Biomediques August Pi i Sunyer (IDIBAPS) • Karolinska Institutiet • University of Verona • Charité –Universitätsmedizin Berlin • HudsonAlpha Institute for Biotechnology • IMIDomics • Zabala Innovation https://doctis.eu/project/consortium/
Contact Details
Project Coordinator, Vall d’Hebron Institut de Recerca (VHIR) Barcelona, Spain info@doctis.eu
Contact: https://doctis.eu/contact/
Dr. Sara Marsal, MD PhD, is the Head of the Rheumatology Service at Vall Hebron University Hospital, founder and director of the Rheumatology Research Group and the IMID-Biobank at Vall Hebron Research Institute, and professor of Rheumatology at the Autonomous University of Barcelona. She is Co-Founder and Chief Medical Officer of IMIDomics, Inc.
Antonio Julià, PhD is the Head of the Rheumatology Group at Vall d’Hebron Research Institute and Chief Data Scientist at IMIDomics. He is an expert in using genomic approaches to characterize the basis of IMIDs. He has coordinated bioinformatics and clinical data analysis for several largescale public-private partnership projects focused on translational research in IMIDs, utilizing high-throughput technologies and nationwide patient collections.
