Disorders of the brain are a major source of disability, and place an enormous burden on society. Currently, many first-line treatments are non-specific, invasive, or cause side-effects. Non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), have been shown to offer a safe treatment alternative, with rTMS first clinically approved for major depression in 2007. Unfortunately since then, translation to other disorders has been slow, mainly due to the lack of reliable methods to identify where in the brain to stimulate. Lesion network mapping (LNM) is a method recently introduced to address this problem. LNM works by mapping the connections of causative brain lesions, converging upon a small number of commonly connected locations in the brain. LNM has localised abnormal networks in over 40 different disorders. However, as yet no study has tested whether these networks respond to treatment. Therefore, the aim of this study is to conduct a clinical trial testing whether rTMS delivered to a specific site in the somatosensory cortex identified in our previously published LNM study (Corp et al., 2019, Brain) results in treatment benefit for cervical dystonia patients. Cervical dystonia is an ideal test case, as changes in abnormal neck movement symptoms are easily measurable, and this somatosensory location is on the surface of the brain, so easily reachable with rTMS. We will employ a randomised, sham-controlled, double-blind, crossover clinical trial, with 30 patients receiving 10 daily sessions of real and sham rTMS. Before and after the brain stimulation, we will collect clinical, behavioural, and physiological data to measure patients’ response to the intervention. Improvement in cervical dystonia symptoms after brain stimulation would serve as proof of the principle that LNM can effectively identify therapeutic targets, potentially unlocking safe and effective treatment protocols for a range of brain disorders.

The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 1 and 2a trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement. To develop the world’s first rigorously proven, effective treatment of DDD, RESPINE aims to assess, via a multicentre, randomized, controlled, phase 2b clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly (within 3 months) and sustainably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised. The transfer to the clinic will be prepared at a cost below 10k€ thanks to the strategy of production of allogenic cells, automation & EU standardisation. At the end of the RESPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs.

The GRACE integrated solution aims to transform the healthcare ecosystem by providing essential knowledge and innovative public-private partnership for (1) reorganizing healthcare services (2) with embedded innovative technologies and tools, helping identifying and overcoming barriers and gaps that are now hindering CVD management, ensuring a seamless continuum of care and optimized care pathways. Our vision is that introducing effective health technology and interventions is economically, societally and environmentally sustainable if and only accompanied by a substantial healthcare service re-organization. Accordingly, GRACE will focus on an end-to-end clinical pathway CVD, considering an holistic view of the patient and optimizing healthcare services leveraging on advanced technological solutions. GRACE intervention will be multifold aiming at: (1) guiding strategic policies, (2) drive market innovation, and (3) foster effective healthcare delivery practices in CVD, generating value for patients, healthcare workers and system. GRACE will enable early and personalized interventions, fostering coordination of multidiscipline healthcare teams, triggering more intense and person-specific management using innovative technologies, AI and digital solutions for early detection of red flags, promoting patient empowerment, while comprehensively containing CVD risk factors and burden. A multidisciplinary consortium of experienced and competitive partners will implement this vision and implement the proposed solution in a novel multidiscipline manner.

The healthcare sector is hindered by several barriers that hamper the application of circular economy principles (e.g. the safety restrictions of the domain limit the use of recycled materials due to the need of materials biocompatibility, and safety in products to be used in the human body). Led by a multidisciplinary consortium of 39 partners (plus 13 industry affiliates) from 15 EU countries plus UK and USA, ENKORE aim to tackle challenges and develop an ecoDesign framework that supports the development of safe and environmental compliant devices eco-responsible packaging, which minimize the environmental impact, reduce the carbon footprint, and maximize the use and preservation of resources. The main goal is to connect the design of the medical devices packages with the end-of-life stage, thus the technologies that support circularity are taken into account at the medical device conception stage. ENKORE framework will be validated in 5 Reference Use Cases (RUCs), led by 5 different health regions that bring HPCs and policy maker, 3 large EU hospitals and the reference network for European Regional and Local Health Authorities (EUREGHA). The project developments and RUCs are supported by several associations and NGOs, a packaging manufacturer and a group of SMEs and researchers, specialists in circularity, LCA, social sciences, environment, circularity, and materials. The validation of the framework shall provide evidence to work with policymakers, creating new or revised standards and create tangible/quantitative evidence. Policy making and regulatory engagement will be strongly performed. The methods and tools comprise Environmental and Social Life Cycle Assessment (ELCA/SLCA), Circularity Calculator (CC) and Digital Product Passport (DPP) approaches, which could be adapted during the second stage of the proposal.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly form of cancer that is on the rise due to various factors, including an aging population and unhealthy lifestyles. Regrettably, PDAC is among the top cancer killers, with a dismal five-year survival rate of less than 10%. The lack of adequate screening programs is a significant factor contributing to this dire statistic. However, the identification of PDAC in its early stages could help reduce the mortality rate by as much as 80%. The project LASERBLOOD (Biophotonic Nanoparticle-enabled Laser Blood Test for Early Detection of Pancreatic Cancer) aims to develop an in vitro diagnostic test based on the fluorescence lifetime fingerprint of the personalized protein corona, offering critical information at every stage of PDAC progression. The protein corona (PC) is a coating of bio-molecular substances surrounding nanoparticles when exposed to biofluids. It is both personalized and disease-specific, making it an ideal marker to monitor the variation of nanoparticle PC and correlate it to the development of PDAC. The analysis will use fluorescence lifetime (FL) analysis, a non-invasive, reactant-free, and real-time technique. In the initial phase, the consortium will utilize a mouse model (MKC) to identify the FL fingerprint of protein corona at each stage of PDAC development. The MKC mouse model is genetically engineered to be bioluminescent and develop PDAC in a controlled manner. By linking the development of PDAC observed through bioluminescent imaging to the FL response of PC in blood samples, the consortium will provide an unprecedented fingerprint of the disease's progression from its first occurrence. At a second stage, the project will validate on humans the use of the FL fingerprint of protein corona as a tool for the early diagnosis of PDAC. The findings will provide the scientific and technological foundation for the development of an in vitro PDAC test for large scale screening of the population.