Bipolar disorder (BD) is a prevalent mental disorder and a leading cause of suicide. Lithium (Li) is the key mood stabilizer for prevention of BD relapse and suicide. Whilst many cases become asymptomatic with Li treatment, the majority show sub-optimal response. Identifying biomarkers for predicting Liresponse would enable personalization of treatment, define criteria for stratification of BD cases and further refine the clinical response phenotype. The objectives of this proposal are to (i) improve outcomes of bipolar I disorder (BDI) cases prescribed Li through the application of stratified approaches; (ii) optimize the early prediction of lLi response using a set of multi-modal biomarkers (“blood omics”, Magnetic Resonance Imaging and Li7-Magnetic Resonance Imaging derived-markers); (iii) develop a multidisciplinary multinational network of experts to undertake this and future projects on personalized diagnostics and therapeutics; and (iv) implement new, powerful technologies to characterize brain Li distribution and the blood molecular signature of Li in responders and non-responders. This cutting edge approach will identify the eligibility criteria for treatment with Li in BD in terms of response, safety and tolerability. The assessment of each putative biomarker (singly and combined) will be guided by preliminary findings already obtained by R-LiNK; our expertise will allow exploratory analyses and innovative modelling of multi-modal data. Likely impacts include improved outcomes and quality of life for BDI cases; development of a screening tool for clinicians; and an evaluation of the cost-effectiveness of this stratified approach. The network will develop new avenues of research on Li mechanisms of action and disease mechanisms; our industrial partnerships will enable development of medical devices to improve treatment adherence and patient’s autonomy, diagnostic kits, and tools based on the molecular signature in treatment responders.

Leishmania causes devastating human diseases – leishmaniases - representing an important public health problem in the Mediterranean basin and declared as emerging diseases in the EU due to climate change and population displacement. The LeiSHield-MATI consortium will for the first time investigate in an integrative fashion the complex parasite-vector-host interplay in cutaneous leishmaniasis affecting Morrocco, Algeria, Tunisia, and Iran (MATI), using field isolates and human clinical samples. The ultimate goal of our project is to identify genetic factors selected during natural infection and to understand how the complex parasite-vector-animal interaction impacts clinical outcome in infected patients. This goal will be achieved through a highly ambitious secondment plan between all partners, and the organization of courses and workshops to train the next generation of scientists generating a long-term impact on the research capacities in endemic areas. Capitalizing on complementary infrastructures of its EU, African and Asian partners and their expertise in molecular parasitology, epidemiology, systems level analyses, bioinformatics, computational biology, immunology, dermatology, field studies, and public health, our project will drive important innovation in clinical research, strengthen capacities in disease endemic regions, inform authorities on control measures, and raise awareness in all partner countries on this emerging EU public health problem. The highly inter-disciplinary and inter-sectorial structure of LeiSHield-MATI, and its powerful integrative and comparative approach is novel in parasitic systems and will drive a unique bio-marker discovery pipeline for the future development of new prognostic and diagnostic tools, as well as novel preventive and therapeutic measures that will ensure long-term collaboration, promote scientific and commercial self-sustainability of its partners, and will have an important impact to improve public health.

Acobiom is a French Biotech SME (SAS, 8 employees). Since its foundation, June 1999, Acobiom has always been at the forefront of medical innovation, in particular in biomarker discovery and diagnostic development, thanks to its expertise and knowledge in genomics, transcriptomics, bioinformatics, and data science. In 2011, Acobiom began working to address the problem of pancreatic cancer. Pancreatic cancer is currently the 4th leading cause of cancer death in Western Countries. If no action is taken, it will rise to be second in 2020. For nearly 80% of patients (~51K and ~150K in USA and EU patients in 2017), diagnosis occurs at an advanced, non-surgical stage, making them incurable. The high mortality rate, with more than 95% of patients dead at 5 years, versus 13% for breast cancer, is partly due to the difficulty to diagnose, but also because of the lack of stratification of patients and a limited choice for treatments in the current decision-making process. There are currently three major chemotherapy regimens for the pancreatic cancer, and up until now, the decisional algorithm in metastatic pancreatic ductal adenocarcinoma (PDAC) management does not mention pharmacogenomics biomarkers, needed to stratify patient populations and to choose the best treatment with the best clinical effectiveness for a given patient. These regimens have very different toxicities profiles which factors in to which regimen is recommended. Through ImOPac project, Acobiom aims to implement an innovative approach to improve personalized pancreatic cancer management in the decision-making process of PDAC, by using biomarkers to help in the patient stratification. This approach is the GemciTest, a non-invasive test based on an 11-gene blood signature score. Thanks to this innovation, Acobiom has an opportunity to create an EU new market estimated at 360 M€, and leading to a 34 M€ turnover by 2024.