Non-alcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, associated with metabolic and cardiovascular complications and morbid mortality. The disease spectrum covers from a simple steatosis to non-alcoholic steatohepatitis (NASH). With estimated 25% of population having NAFLD, it makes it the most common liver disease in the world. While diagnosing and stratifying NAFLD and NASH is of high priority to identify subjects with increased risk for cardio-vascular complications, the gold standard of current diagnostics is an invasive liver biopsy. Recently discovered extracellular vesicles (EVs) have shown high potential to become novel source of non-invasive biomarkers as they are loaded with the same molecular information as their parental cells (proteins, metabolites, RNAs). Molecular information of liver-derived EVs could be a great source of liver specific biomarkers, that are obtainable in circulation and are suitable for non-invasive diagnostics. However, analysing biochemical/omics profiles of tissue specific EVs in biofluids is an unsolved challenge and has not been realized in routine clinical diagnostics yet. In this project ALIVE we propose to develop a technology capable of isolating cell and organ specific EVs from biological samples and perform their omics analysis and to apply this technology in the proof-of-concept investigation of potential biomarkers of liver disease in blood. ALIVE is a great opportunity for the experience researcher Dr. Andrea Capuano to gain new technical and transferable skills, exchange knowledge with the host, an innovative European startup EXIT071 and secure a leadership position in innovative ecosystem of Europe.

GRIP on MASH will address the unmet public health need of reducing disease burden and comorbidities associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD). Together with seven medical technology, pharmaceutical and biotechnology companies, we will devise a sustainable and scalable GRIP on MASH Platform that will enable access to at-risk patients developing or having MASLD through the early detection of this condition at the primary care level. This Platform will allow A) the early detection of patients with MASLD: distributed in 12 European Centers of Excellence (CoEs), 10,000 patients at high risk of MASLD - defined as patients with type-2 diabetes mellitus, metabolic syndrome, obesity or arterial hypertension - will be screened and characterized; B) better patients’ stratification: the Platform will comprise artificial intelligence-based decision support tools that will make use of existing and novel biomarkers/biomarker combinations. Their predictive accuracy will be tested at the primary care level; there we will perform multi-OMICs analysis (proteomics, lipidomics, metabolomics, genomics, metagenomics and fluxomics) in fasted blood samples and we will explore imaging biomarkers/organ-on-a-chip to find future non-invasive diagnostic alternatives for the current standard (liver biopsies); and C) personalized lifestyle advice, by exploring evidence-based lifestyle features and the effect of nutritional recommendations: among the cohorts at the CoEs, we will use validated questionnaires to assess physical activity, diet, sleep, smoking, alcohol consumption, and perception of stress. Integrating patients’ perspectives with the participation of two patient organizations, the trustworthiness and sustainability of our GRIP on MASH Platform will be assessed by investigating potential economic, ethical and regulatory barriers to its future adoption. GRIP on MASH will change healthcare practice in MASLD and reduce the disease burden for patients.

EXIT071 (EXosome Isolation Tool) is a Leiden based startup developing pioneering technology for the analysis of novel biomarkers exosomes. We are a young yet experienced startup with great motivation and ambition to bring a very much needed technological solution to a highly potential exosomes market. This funding opportuning Women TechEU from Horizon Europe comes at the perfect time for EXIT071. The technology is already proven to perform, plan, partners and finances for technological development are secured and the team is coming together. In this project EXO4EU – EXOsome analysis business for inclusive innovation ecosystem in EU, we propose activities for in-depth makeover of our business plan and strategy enhancement. The networking opportunities offered by InvestEU and the Enterprise Europe Network are very appealing for our early integration into the European ecosystem of innovation. Being mentored and coached under the Women Leadership Programme will have a bespoken value for the passionate founder and quickly learning CEO, Dr. Yuliya Shakalisava, who is making a challenging yet exciting career transitioning from research to business.