Periodic Reporting for period 1 - SIGNATURE (SInGle cells iN AuToimmUne inflammatoRy disEases)
Periodo di rendicontazione: 2023-01-01 al 2024-12-31
Autoimmune disorders are highlyImmune-mediated disorders are highly heterogenenous entities for which the mechanisms of disease progression and therapeutic responses are only recently beginning to be understood. The patterns of transcriptome are the reflection of distinct cell types that are involved in the development of the disease process. Our plan is to approach the diseases beginning from a global view that allows us to then come down to the most relevant cell types in tissues and blood. In addition, by understanding disease heterogeneity and diseases similarities, we can also identify the best pathways to be targeted with specific biological treatments.
The diseases involved are systemic lupus erythematosus, rheumatoid arthritis, asthma. Based on a unique ongoing platform of clinical groups across Europe and specialists in cell and molecular profiling, imaging analyses, single cell sequencing and analysis, we will identify the molecular basis of each of the diseases heterogeneity, the mechanisms of treatment non responsiveness, and develop a specialized training program where students will be able to visualize the overall work from design to analysis of the data and become engaged in the unique multi-disciplinariry of this platform.
The platform will have available existing clinical studies and clinical trials, but will be also producing new data from prospective studies where samples and tissues for each disease, based on the appropriate indications will be obtained with special protocols, for the study. The engaged students will be permeated by the latest advances in not one, but several new approaches and systems biology modelling, and develop out-of-the-box concepts where diseases can be viewed not as separate clinical entities but as novel groups of shared molecular and cellular patterns that impinge on specific tissues by specialized cell types.
The diseases involved are systemic lupus erythematosus, rheumatoid arthritis, asthma. Based on a unique ongoing platform of clinical groups across Europe and specialists in cell and molecular profiling, imaging analyses, single cell sequencing and analysis, we will identify the molecular basis of each of the diseases heterogeneity, the mechanisms of treatment non responsiveness, and develop a specialized training program where students will be able to visualize the overall work from design to analysis of the data and become engaged in the unique multi-disciplinariry of this platform.
The platform will have available existing clinical studies and clinical trials, but will be also producing new data from prospective studies where samples and tissues for each disease, based on the appropriate indications will be obtained with special protocols, for the study. The engaged students will be permeated by the latest advances in not one, but several new approaches and systems biology modelling, and develop out-of-the-box concepts where diseases can be viewed not as separate clinical entities but as novel groups of shared molecular and cellular patterns that impinge on specific tissues by specialized cell types.
The driving concept of the network SIGNATURE is the identification of the mechanisms of response and non-response to therapy in autoimmune diseases, mainly systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA), using single-cell technologies and advanced bioinformatics. SIGNATURE network is training 10 doctoral candidates (DC) in the essential enabling technologies that are urgently needed in the field: single cell technologies, liquid biopsy, deep profiling, spatial data analysis, multi-omic data integration and systems immunology. Within this action the DC are acquiring a global view of these diseases with the aim of understanding the heterogeneous molecular nature of the clinical diseases and to predict the best treatment for every single patient based on the experimental evidence. This training network is integrated into the European consortium 3TR (www.3tr-imi.eu ). This multicentric project is financed under the Innovative Medicine Initiative, bringing together 59 partners from 15 countries and 8 big pharma companies. This unique research environment brings together clinical centers, academia, biotech companies, pharma industry and patient associations, thus providing a quite unique international, interdisciplinary and intersectional collaborative framework, exposing the ERs to academic and non-academic environments.
Scientific impact.
● Better understanding of the link between the molecular characteristics of disease and non-response to target drug treatments. This will increase the likelihood of treatment success and thus decrease costs to patients (side effects) and society.
● Advances in the establishment of early markers of response, allowing the identification of disease endotypes that may be responsive to different therapies.
Economy/technological impact.
SIGNATURE is inclusive and recognizes the advantages of small-medium enterprises (SME), their importance to the European economy and their views and perspectives. For this reason, it has included several SMEs: Altra-Bio, AtrysHealth, OmniScope, Fluidigm. They are enterprises with very specific expertise and knowledge, and whose input at this point is important. Thus, the impact of SIGNATURE is not only limited to the pharmaceutical industry and academia, but also is improving the advancement perspectives of these SMEs. SIGNATURE has become a proof-of-concept of the integration of medicine into molecular entities, creating a new paradigm never seen before, and new as detailed information is being gained on what mechanisms are relevant for treatment responses in 3 diseases. The combination of excellent academic institutions with world-leading industrial partners through the IMI public private partnership 3TR is enabling a substantial increase in the competitiveness of the involved partners.
Societal impact.
Autoimmune and inflammatory diseases are difficult to diagnose. Many patients remain for years without a diagnosis. The progression of these diseases is unpredictable, and when damage ensues it is, at times, fatal (SLE), directly lethal (MS) or chronically disabling (RA), leading to a combined substantial impact on premature mortality. As patients are usually in their mid-ages or even very young when diagnosed, this results in an enormous cost/patient for the European health systems and an important reduction in patient quality of life, endangering their social and working relations, everyday life, and their self-esteem. Understanding molecular trajectories to guide treatment selection is essential to ensure least toxicity, be able to predict relapses to limit their appearance, and to predict the patients who are at greater risk to develop severe damage, and prevent such damage. Our project participants are working to provide Europeans, including the increasing numbers of older people, with more efficient and effective medicines and treatments. By better targeting available therapies to those most likely to respond, SIGNATURE will substantially decrease costs associated with treatments which do not show the desired effect. Furthermore, we will decrease co-morbidities through targeted treatment, which in turn decreases costs by reducing expensive additional health care.
● Better understanding of the link between the molecular characteristics of disease and non-response to target drug treatments. This will increase the likelihood of treatment success and thus decrease costs to patients (side effects) and society.
● Advances in the establishment of early markers of response, allowing the identification of disease endotypes that may be responsive to different therapies.
Economy/technological impact.
SIGNATURE is inclusive and recognizes the advantages of small-medium enterprises (SME), their importance to the European economy and their views and perspectives. For this reason, it has included several SMEs: Altra-Bio, AtrysHealth, OmniScope, Fluidigm. They are enterprises with very specific expertise and knowledge, and whose input at this point is important. Thus, the impact of SIGNATURE is not only limited to the pharmaceutical industry and academia, but also is improving the advancement perspectives of these SMEs. SIGNATURE has become a proof-of-concept of the integration of medicine into molecular entities, creating a new paradigm never seen before, and new as detailed information is being gained on what mechanisms are relevant for treatment responses in 3 diseases. The combination of excellent academic institutions with world-leading industrial partners through the IMI public private partnership 3TR is enabling a substantial increase in the competitiveness of the involved partners.
Societal impact.
Autoimmune and inflammatory diseases are difficult to diagnose. Many patients remain for years without a diagnosis. The progression of these diseases is unpredictable, and when damage ensues it is, at times, fatal (SLE), directly lethal (MS) or chronically disabling (RA), leading to a combined substantial impact on premature mortality. As patients are usually in their mid-ages or even very young when diagnosed, this results in an enormous cost/patient for the European health systems and an important reduction in patient quality of life, endangering their social and working relations, everyday life, and their self-esteem. Understanding molecular trajectories to guide treatment selection is essential to ensure least toxicity, be able to predict relapses to limit their appearance, and to predict the patients who are at greater risk to develop severe damage, and prevent such damage. Our project participants are working to provide Europeans, including the increasing numbers of older people, with more efficient and effective medicines and treatments. By better targeting available therapies to those most likely to respond, SIGNATURE will substantially decrease costs associated with treatments which do not show the desired effect. Furthermore, we will decrease co-morbidities through targeted treatment, which in turn decreases costs by reducing expensive additional health care.