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Basel, Switzerland

Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.19M | Year: 2016

Understanding mechanisms underlying comorbid disorders poses a challenge for developing precision medicine tools. Psychiatric disorders are highly comorbid, and are among the last areas of medicine, where classification is driven by phenomenology rather than pathophysiology. We will study comorbidity between the most frequent psychiatric conditions, ADHD, mood/anxiety, and substance use disorders, and a highly prevalent somatic disease, obesity. ADHD, a childhood-onset disorder, forms the entry into a lifelong negative trajectory characterized by these comorbidities. Common mechanisms underlying this course are unknown, despite their relevance for early detection, prevention, and treatment. Our interdisciplinary team of experts will integrate epidemiologic/genetic approaches with experimental designs to address those issues. We will determine disease burden of comorbidity, calculate its socioeconomic impact, and reveal risk factors. We will study biological pathways of comorbidity and derive biomarkers, prioritizing two candidate mechanisms (circadian rhythm and dopaminergic neurotransmission), but also leveraging large existing data sets to identify new ones. A pilot clinical trial to study non-pharmacologic, dopamine-based and chronobiological treatments will be performed, employing innovative mHealth to monitor and support patients daily life. Integration of findings will lead to prediction algorithms enhancing early diagnosis and prevention of comorbidity. Finally, we will screen to repurpose existing pharmacological compounds. Integrating complementary approaches based on large-scale, existing data and innovative data collection, we maximize value for money in this project, leading to insight into the mechanisms underlying this comorbidity triad with its huge burden for healthcare, economy, and society. This will facilitate early detection and non-invasive, scalable, and low-cost treatment, creating opportunities for substantial and immediate societal impact.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-2 | Award Amount: 3.85M | Year: 2012

OPTIMISTIC is a proposal for a European collaborative project of doctors, scientists, relevant stakeholders (TREAT-NMD, patient organizations) and SMEs with the aim to improve clinical practice for patients suffering from a rare, inherited, and neglected disease, myotonic dystrophy type 1 (DM1). It is one of the most variable human diseases with complex, multi-systemic and progressively worsening clinical manifestations. Despite the huge impact of DM1 on the daily life of both patients and their family members, DM1 patients fail to receive the quality of healthcare that is available as they are not assertive users of the health care system. There is no cure for DM1. The aim of treatment is to relieve impairments, reduce limitations and support participation in everyday activities. Based on our DM1-specific model which shows that physical activity and experienced fatigue are main determinants of DM1 health status (Kalkman 2007), OPTIMISTIC investigates the effect of cognitive behavioural therapy (CBT) in combination with exercise training to improve functional capacity and to stimulate an active lifestyle. OPTIMISTIC compares the outcome of a treatment regimen with regular management in a multi-centre, assessor-blinded, randomized controlled trial, designed to 1) result in evidence-based clinical guidelines on exercise and cognitive behavioural therapy in DM1, 2) capture clinically meaningful changes in existing and novel outcome measures, and 3) identify both individual and composite biomarkers as surrogate treatment outcome measures that are reflective of the disease state. There is an urgent need for an European clinical trial infrastructure for DM1. High prioritization of this is required to enhance the speed of clinical development of new putative DM1 therapeutics approaching the market. OPTIMISTIC will provide this and safeguard the rapid uptake of the developed clinical guidelines ensuring improvements in DM1 care and quality of life.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-3 | Award Amount: 5.84M | Year: 2014

Conduct Disorder (CD) is the key paediatric disorder characterized by severe aggression. It is heterogeneous, and our understanding of the neurobiology to subtype aggression is limited. MATRICS is a multidisciplinary consortium of academic partners and SMEs that focuses on the subtyping of aggression both within CD and of the broader cross-disorder trait of aggression. MATRICS will test the hypothesis that reactive and instrumental aggression result from aberrant autonomic reactivity coupled to the differential impairment of three basic neural functions: 1) regulation of control mechanisms of aggression, 2) emotional value rating of others, and 3) empathy and moral decision making. MATRICS will employ the same psychological tasks assessing 1), 2) and 3) in animal aggression models and human CD samples concurrent with the assessment of neural, neurochemical, (epi)-genetic and autonomic nervous system markers. These data will be integrated with matching expression profiling from neurons derived from CD IPSCs. MATRICS also examines how environmental risks, whether or not they interact with genetic factors, are translated in epigenetic and neural changes. MATRICS will data-mine existing large integrated imaging-genetics cohorts (NeuroIMAGE; IMAGEN) and prospective cohorts (TRAILS; ALSPAC) with follow-up into adulthood and the (epi)genetic profiling of the PERS CD cohort, and collect a large new CD cohort and controls for collection of MRI, (epi)-genetic, biochemical and environmental measures. Bayesian machine learning tools will integrate multi-source and multi-level data, and generate predictive algorithms of persistent aggression into adulthood. MATRICS will identify new potentially druggable targets, develop novel animal models and conduct pilot medication and neuro/biofeedback studies in high-risk and CD patients. MATRICS builds on existing fruitful EU collaborations which maximises feasibility and successful output.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 14.69M | Year: 2013

Cancers are genetic disease arising from the accumulation of multiple molecular alterations in affected cells. Large-scale genomic, transcriptomic and proteomic analyses have established comprehensive catalogues of molecules which are altered in their structure and/or abundance in malignant tumors as compared to healthy tissues. Far less developed are concepts and methods to integrate data from different sources and to directly interrogate gene functions on a large scale in order to differentiate driver alterations, which directly contribute to tumor progression, from indolent passenger alterations. As a consequence, examples of successful translation of knowledge generated from omics approaches into novel clinical concepts and applications are scarce. Pancreatic cancer is a prime example of this dilemma. Representing the 4th to 5th most common cause of cancer related deaths, it is a disease with a major socioeconomic impact. Despite enormous advances in the identification of molecular changes associated with the disease, new treatment options have not emerged. Thus, 5-year survival rates remain unchanged at a dismal 6%, the lowest for all solid tumors. Using pancreatic cancer as a model disease, the goal of this integrative project is to develop novel cellular and animal models, as well as novel strategies to generate, analyze and integrate large scale metabolic and transcriptomic data from these models, in order to systematically characterize and validate novel targets for therapeutic intervention. In addition to the general tumor cell population, special consideration will be given to sub-populations of tumor-initiating cells, a.k.a. tumor stem cells. To this end, the consortium comprises i) SMEs with strong focus on technology development, ii) clinical and academic partners with extensive experience in pancreatic cancer molecular biology and management of pancreatic cancer patients, and iii) technology and data analysis experts from academic groups.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.2-1 | Award Amount: 7.83M | Year: 2014

Background: Hyperinsulinaemic hypoglycaemia (HH) is a potentially lethal disease caused by over functioning beta cells derived from the pancreatic islets of Langerhans. Lethal HH and brain damage is a problem especially in infants with congenital HH. Current therapeutic approaches are associated with severe side effects/morbidity (diabetes, exocrine pancreas insufficiency etc.) considered acceptable in relation to the lethal outcome of HH although massively reducing quality of life and also life expectancy. Aims and objectives: In order to significantly improve therapy of this awful disorder, we propose to develop a simultaneous imaging/therapy platform allowing diagnostic imaging as well as image guided surgical, photodynamic or radiopeptide therapy to selectively resect/destroy diseased beta cells. This platform will enable delivery of patient-individual tailored therapy, increasing cure rate while significantly reducing or even avoiding side effects. The platform will integrate information from pre-clinical imaging for optimal therapy planning with intra-operative imaging for image guided surgery. By implementation of extended field optical coherence tomography, information on a histopathological level will allow increased precision of therapy. Highly innovative photodynamic therapy will enable selective (endoscopic) destruction of diseased beta cells without resection of pancreatic tissue. Outcome: Our highly-innovative integrated imaging/therapy (theranostic) platform will allow diagnosis and monitoring of disease, support and guide therapeutic intervention, predict outcome of intervention and individual prognosis. This technology will massively improve therapy, especially in infants, by improving cure rates while significantly reducing morbidity for improved quality of life and increased life expectancy. We will contribute to the goals of the International Rare Diseases Research Consortium (IRDiRC): 200 new therapies.

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