Sudden cardiac arrest (SCA) causes ~20% of all deaths in Europe. SCA is lethal within minutes if left untreated and survival rates are presently only 5-20%. Therefore, there is a large medical need to improve SCA prevention and treatment. Designing effective individualized prevention and treatment strategies requires knowledge on genetic and environmental risk factors. So far, these efforts have been hampered by the lack of sufficiently large study cohorts of SCA patients with detailed information. Obtaining SCA patient samples is challenging as the condition happens suddenly and unexpectedly. In this project, leading European scientific teams which have created large relevant population cohorts, mostly dedicated to SCA research, join forces to fully exploit available data towards improving SCA management. This will be done by: - Building an unique and growing database of >100.000 (DNA) samples including >20.000 SCA patient samples, by combining existing European databases and infrastructures. - Identifying risk factors (inherited, acquired, environmental) and first-response treatment strategies that may explain the differences in SCA occurrence and survival between European countries - Collaborating with professional networks, such as the European Heart Rhythm Association, and European Resuscitation Council, to translate the outcomes into changes in clinical practice and influencing European health policies on SCA management.

Tinnitus is the perception of a phantom sound and the patient’s reaction to it. Tinnitus remains a scientific and clinical enigma of iTinnitus is the perception of a phantom sound and the patient’s reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden. It affects more than 10% of the general population, whereas 1% of the population considers tinnitus their major health issue. Recent cohort studies show that tinnitus prevalence tends to increase over time and with older age. Assuming that there is no cure to be found, the prevalence estimates in Europe would double by 2050. A large variety of patient characteristics - including genotyping, aetiology, and phenotyping - are poorly understood, because integrated systems approaches are still missing to correlate patient`s characteristics to predict responses to combinatorial therapies. Although genetic causes of tinnitus have been neglected for decades, recent findings of genetic analysis in specific subgroups (gender and phenotype) have highlighted that bilateral tinnitus in men reached a heritability of 0.68. This heritability is close to autism, schizophrenia and Attention Deficit Hyperactive Disorder (ADHD). There is no current consensus on tinnitus treatment. UNITI’s overall aim is to deliver a predictive computational model based on existing and longitudinal data attempting to address the question which treatment approach is optimal for a specific patient based on specific parameters. Clinical, epidemiological, medical, genetic and audiological data, including signals reflecting ear-brain communication, will be analysed from existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance will be tested in a randomized controlled trial (RCT) in which different groups of patients will undergo a combination of therapies targeting the auditory and central nervous systems.

Type 2 diabetes will affect >500 million adults by 2040 and its secondary complications will generate enormous socioeconomic costs - in particular, diabetic kidney disease (DKD), which is already the most common cause of chronic kidney disease. DKD is associated with greatly increased mortality and frequently progresses to end stage renal failure. Pharmacotherapy, dialysis and transplantation represent the mainstay treatments for DKD but are costly and provide only limited protection against adverse outcomes. Mesenchymal Stromal Cell (MSC) therapy is a promising approach to halting the progression of DKD toward end-stage renal failure and may also have ancillary benefits in Type 2 diabetes. In preliminary research, we have demonstrated that a single dose of MSC simultaneously improves kidney function (glomerular filtration rate and albuminuria) as well as hyperglycaemia in animals with DKD. NEPHSTROM will conduct a multi-centre, placebo-controlled clinical trial of a novel MSC therapy for stabilization of progressive DKD, leading to superior clinical outcomes and long-term socioeconomic benefit. A key enabler for this trial is a novel MSC population (CD362+MSC, trade name ORBCEL-M) which delivers higher purity and improved characterisation compared to conventional plastic-adherent MSC. The NEPHSTROM Phase 1b/2a clinical trial will investigate the safety, tolerability and preliminary efficacy of a single intravenous infusion of allogeneic ORBCEL-M versus placebo in adults with progressive DKD. NEPHSTROM investigators will also determine the bio-distribution, mechanisms of action, immunological effects and economic impacts associated with ORBCEL-M therapy for DKD. This research will critically inform the optimal design of subsequent Phase 3 trials of ORBCEL-M. Stabilising progressive DKD through NEPHSTROM’s next-generation MSC therapy will reduce the high all-cause mortality and end-stage renal failure risk in people with this chronic non-communicable disease