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Chronic inflammatory disease is causing an increasing medical and societal burden. Conditions such as inflammatory bowel disease, rheumatoid arthritis and autoimmune conditions are estimated to affect 1 in 10 people in Europe. However, at present, the treatment options available are limited and ineffective, and there are no identified pathways to finding a cure.
The EU-funded SYSCID project has developed an approach to create precise and individualised treatment options for patients with chronic inflammatory diseases. The aim is to enable biomarkers, or disease signatures, to be identified that indicate the presence of disease so that conditions can be diagnosed and treated quickly and effectively.
Initially, this will provide precision medicine and personalised treatment options which can be adjusted to an individual patient’s specific condition. The approach will also help to determine the cause of conditions and the development of cures. The project, which ends in March 2022, is continuing to develop the approach.
‘The project has revealed information about treatment options for patients with inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematodes,’ says project coordinator Philip Rosenstiel of Christian-Albrechts-Universität zu Kiel in Germany. ‘Initial studies into how disease affects the body’s cellular programming has improved our understanding of how some treatment options work.’
Understanding the molecular level
Inflammatory diseases manifest at different molecular layers within the body. SYSCID looks at disease at three of these: the epigenetic or gene expression level, the cell programming or transcriptional level, and the gut bacteria or microbiome level.
The project set out to find core disease signatures in large datasets collected over time. Initial studies monitored over 300 patients undergoing first-time treatment for chronic inflammatory diseases.
This has provided data on cellular programming that can be used to understand how cells influence gene expression. This information has already revealed that treatment with an antibody called vedolizumab modulates patients’ innate disease immunity.
Reprogramming disease
The SYSCID project is following three distinct pathways to innovation. Specifically, it focuses on big-data analysis. Complex statistics and bioinformatics enable clinical details to be derived from the huge datasets collected from patients. This simplified information can be easily interpreted and understood by both clinicians and patients.
Project researchers are also focusing on understanding disease at the single-cell level. This approach aims to enable the identification of biomarkers, easier diagnosis of chronic inflammatory diseases, and a predictive model of disease outcomes.
The project is also hoping to understand the epigenetics – changes in genetic behaviour – that govern the onset of inflammatory diseases. This could enable diseases to be cured by erasing, editing or reprogramming parts of a patient’s genome.
‘SYCID will create a prediction framework for disease outcome and guide therapy decisions on an individual patient level,’ says Rosenstiel. ‘This will mean that the right therapy is chosen at the right time. The consortium is also targeting new therapy approaches to ‘reprogramme’ disease through epigenome editing. In this way, diseases will not only be managed but cured.’
The project brings together experts from major scientific disciplines, such as genomics, with clinicians, gastroenterologists and rheumatologists from across Europe. These key players have set up collaborations to enable rapid progress.