Current orthopaedic treatments permit spontaneous bone regeneration to unite and heal 90% bone injuries. Non-union associates pain and disability, often requiring biological enhancement. Regenerative medicine research suggests to the general public that alternative treatments based on advanced therapy medicinal products (ATMP) are already available. However, early clinical trials only explore its potential benefit. Underreported results and absence of early trial confirmation in adequately powered prospective randomized clinical trials (RCT) indicate that evidence is not available to transfer any technique into routine clinical application. This ORTHOUNION Project was developed from FP7-Project (REBORNE). Its results confirmed 92% bone healing rate (Gómez-Barrena et al, 2016 submitted manuscript) with an autologous ATMP of GMP expanded bone marrow derived human MSC in non-unions, where the reported bone healing rate after surgery with standard bone autograft is 74%. Any further development requires adequately powered prospective RCTs. This will be the main aim of ORTHOUNION: to assess clinically relevant efficacy of an autologous ATMP with GMP multicentric production in a well-designed, randomized, controlled, three-arm clinical trial under GCP, versus bone autograft, gold-standard in fracture non-unions. A non-inferiority analysis will evaluate if cell dose can be lowered. ATMP has been authorized by the National Competent Authorities of the participating countries in 3 previous trials (REBORNE) and will be monitored by ECRIN-ERIC to ensure quality and credibility of RCT results. Secondary aims include innovative strategies to increase manufacturing capacity and lower costs to pave translation into routine clinical treatments, biomaterial refinement to facilitate surgery, personalized medicine supportive instruments for patient selection and monitoring, and health economic evaluation. Results in this project may help define the future of bone regenerative medicin

The objective of the project is to develop novel curative concepts for chronic hepatitis B (CHB). Specific aims will be to: 1) improve the rate of functional cure of CHB by boosting innate immunity with immune modulators and stimulating adaptive immune responses with a novel therapeutic vaccine; ii) characterize immune and viral biomarker signatures for patient stratification and treatment response monitoring; iii) integrate biological and clinical data to model the best combination treatment for future trials; iv) model the effectiveness of novel curative therapies with respect to disease spectrum, patient heterogeneity, and constraints of National Health Systems. The project organization will combine: i) a Proof of Concept clinical trial of a combination of 2 novel compounds stimulating innate immunity; ii) a preclinical immune therapy platform in humanized mice combining immune-modulatory strategies to stimulate innate immunity, rescue exhausted HBV-specific T cells and generate anti-HBV adaptive responses; iii) extensive virologic and immune profiling to identify correlates of cure in patients, iv) the integration of large biological and clinical datasets, v) a cost-effectiveness modelling of new therapeutic interventions, vi) project management, vii) results exploitation and dissemination. The proposal responds to the work program by: i) including the evaluation of emerging concepts in drug and vaccine development to discover a curative strategy for CHB, a major public health concern for Europe, ii) capitalizing on knowledge of host-pathogen interactions to develop novel immune-based therapies, iii) considering age, gender and viral genetic variations, iv) comprising a clinical trial and a pre-clinical platform for the discovery of novel immune interventions, and selection of relevant biomarkers for validation in established clinical cohorts, v) addressing conditions for effective uptake of the new curative interventions by National Health Systems.

Neurodegenerative diseases (NDs), such as Dementia, Parkinson’s and motor neuron diseases, are a major and continuously growing worldwide health issue, particularly devastating for patients and their families. Yet, no cures are available, largely due to the lack of knowledge of ND pathogenic mechanisms. Strikingly, co-occurrence of several NDs in the same patient or family, and evidence that mutations in the same gene lead to several NDs are indicating that common molecular pathways are involved across NDs. Elucidating these shared mechanisms could have a major impact for the treatment and the prevention of this spectrum of NDs. Leveraging on our expertise in studying autonomous and non-autonomous mechanisms of NDs, we propose an innovative, multinational and multidisciplinary collaborative research project to perform network analyses across NDs and identify key common underlying mechanisms. The CROSS-NEUROD project is focused on: 1) the development of integrative in vitro 3D disease models (mini-brains, mini-spinal cords, and motor unit) to elucidate common cellular and molecular pathways across NDs; 2) the validation in animal models of the therapeutic targets identified. To achieve these aims we will consolidate research partnerships through staff exchanges and networking activities between 3 European research organizations, two of which from Italy, one from Greece, and a partner, USA. The project is based on a 4 years coordinated joint program of exchanges of researchers for short periods. It has been developed from active bilateral cooperation between individual countries and partners and represents the natural progression of our previously funded and successfully completed EU 7PQ IRSES grant “No-MND” (2013 call). Our ongoing research programs are well supported by funding. The RISE scheme provides a unique opportunity to integrate ongoing collaboration activities into a coherent program addressing an issue of high priority for public health both in EU and USA.

Erythrocytes represent an estimated 84% of all cells in the human body. During circulation, they experience a huge variety of physical and chemical stimulations, such as pressure, shear stress, hormones or osmolarity changes. These signals are translated into cellular responses through ion channels that modulate erythrocyte function. Ion channels in erythrocytes have only recently been recognised as the utmost important players in physiology and pathophysiology. Despite this awareness, their signalling, interactions and concerted regulation, such as the generation and effects of 'pseudo action potentials', remain elusive. INNOVATION proposes a systematic, conjoined approach using molecular biology, in vitro erythropoiesis, state-of-the-art electrophysiological techniques, methods to detect erythrocyte functionality and patient samples (channelopathies and other red blood cell-related diseases) to decipher and make use of ion channel functions in terms of disease treatment concepts. We need to overcome the challenges that hinder the gain of knowledge within the field, using genetic manipulation of progenitors, cell differentiation into erythrocytes, statistically efficient electrophysiological recordings of ion channel activity that are limited by the heterogeneity of the cell population (120 days of lifespan without any protein renewal) or access to large cohorts of patients. Our multidisciplinary team includes biophysicists and cell biologists to investigate erythrocyte characteristics and bioengineers to develop diagnostic devices. INNOVATION involves academic research centres as well as diagnostic labs providing patient samples, blood bank research centres developing cultured transfusion products and SMEs that provide and develop diagnostic tools or innovative therapeutic red blood cell products. The consortium offers on-site training, secondments and a variety of courses in transferrable and complementary skills to 10 doctoral candidates.