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Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2011.2.2.1-2 | Award Amount: 24.91M | Year: 2012

The goal of this proposal (INMiND) is to carry out collaborative research on molecular mechanisms that link neuroinflammation with neurodegeneration in order to identify novel biological targets for activated microglia, which may serve for both diagnostic and therapeutic purposes, and to translate this knowledge into the clinic. The general objectives of INMiND are: (i) to identify novel mechanisms of regulation and function of microglia under various conditions (inflammatory stimuli; neurodegenerative and -regenerative model systems); (ii) to identify and implement new targets for activated microglia, which may serve for diagnostic (imaging) and therapeutic purposes; (iii) to design new molecular probes (tracers) for these novel targets and to implement and validate them in in vivo model systems and patients; (iv) to image and quantify modulated microglia activity in patients undergoing immune therapy for cognitive impairment and relate findings to clinical outcome. Within INMiND we bring together a group of excellent scientists with a proven background in efficiently accomplishing common scientific goals (FP6 project DiMI,, who belong to highly complementary fields of research (from genome-oriented to imaging scientists and clinicians), and who are dedicated to formulate novel image-guided therapeutic strategies for neuroinflammation related neurodegenerative diseases. The strength of this proposal is that, across Europe, it will coordinate research and training activities related to neuroinflammation, neurodegeneration/-regeneration and imaging with special emphasis on translating basic mechanisms into clinical applications that will provide health benefits for our aging population. With its intellectual excellence and its crucial mass the INMiND consortium will play a major role in the European Research Area and will gain European leadership in the creation of new image-guided therapy paradigms in patients with neurodegenerative diseases.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.3-1 | Award Amount: 8.25M | Year: 2012

Background: A significant proportion of pre-diabetics, show macro and micro vascular complications associated with hyperglycaemia. Although many trials have demonstrated the efficacy of lifestyle and pharmaceutical interventions in diabetes prevention, no trial has evaluated the extent to which mid- and long-term complications can be prevented by early interventions on hyperglycaemia. Aims: To assess the long-term effects on multiple complications of hyperglycaemia of early intensive management of hyperglycaemia with sitagliptin, metformin or their combination added to lifestyle intervention (LSI) (diet and physical activity), compared with LSI alone in adults with non-diabetic intermediate hyperglycaemia (IFG, IGT or both). Study Design: Long-term, multi-centre, randomised, partially double blinded, placebo controlled, phase-IIIb clinical trial with prospective blinded outcome evaluation. Participants will be randomised to four parallel arms: 1) LSI \ 2 placebo tablets/day; 2) LSI \ 2 Metformin tablets of 850 mg/day; 3) LSI \ 2 Sitagliptin tablets of 50 mg/day; 4) LSI \ 2 tablets of a fixed-dose combination of Sitagliptin 50mg and Metformin 850 /day. Active intervention will last for at least 3 years, and additional follow-up up to 5 years. Setting and population: Males and Females with pre-diabetes (IFG, IGT or both) aged 45 to 74 years selected from primary care screening programs in 15 clinical centres from 12 countries: Australia, Austria, Bulgaria, Germany, Greece, Italy, Lithuania, Poland, Serbia, Spain, Switzerland and Turkey. (N=3000) Main Outcomes: The primary endpoint is a combined continuous variable: the microvascular complication ndex (MCI) composed by a linear combination of the Early Treatment Diabetic Retinopathy Study Scale (ETDRS) score (based on retinograms), the level of urinary albumin to creatinine ratio, and a measure of distal small fibre neuropathy (sudomotor test by SUDOSCAN), measured during baseline visit and at 36th and 60th month visits after randomisation. In addition, this project will include the evaluation of early novel serological biomarkers of systemic inflammation, early micro-vascular damage, non-alcoholic fatty liver disease, insulin sensitivity and insulin secretion, and measures of quality of life, sleep quality (somnograms) and neuropsychological evaluation. Vascular function and structure will be evaluated in a subset of participants (n=1000), including cIMT and microvascular endothelial function measured by EndoPAT. Expected results: By evaluating the effect of aggressive treatments in pre-diabetes for the early prevention of diabetes complication, this project has the potential of changing the current paradigm of early management of hyperglycaemia. The ultimate goal is the development of a standardized core protocol for the early prevention of microvascular and other complications, impacting social cost as a result not only in health care, but also in disabilities at work.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 4.19M | Year: 2014

Knee Osteoarthritis (KOA) is the most common chronic musculoskeletal disorder, currently affecting over 8 million people within the EU, for which currently no cure is available. Adverse biomechanics, affected through some of the major health issues of our time (ageing, obesity, sedentary lifestyle) lie at the heart of the disease. The research theme of the KNEEMO ITN is towards targeted and tailored interventions for KOA, and focuses on identifying the right patients for the right treatment at the right time. Research areas include anatomy, musculoskeletal modelling, prevention and early identification of patients, epidemiology, biomechanical mechanisms, and intervention studies. The KNEEMO training programme combines existing best practices from consortium members and is designed to equip researchers with skills and knowledge specific to the research field (KOA anatomy, pathology and disease mechanisms, musculoskeletal modelling, functional assessment, KOA interventions), generic research skills (epidemiology, methodology, statistics, clinimetrics, ethics), and complementary training (entrepreneurship, project management, product development, intellectual property issues). At the individual level, training will be provided through direct research project supervision and intersectoral exchange visits and secondments. At the network level, regular workshops, courses, and summer schools will be scheduled. Additionally, web-based seminars will be provided and a social media virtual learning environment will be available for continuous supervision, peer-support and expert help. Dissemination and outreach activities will also be undertaken to showcase project results and to communicate with both the scientific community and the general public to promote the importance of research and to raise public awareness of the Marie Curie Actions.

PACE aims to transform the treatment of patients suffering from critical limb ischemia (CLI), a disease with high medical need, because of limited treatment options and poor outcome by applying a novel, off-the-shelf allogeneic placenta-derived stromal cell product (PLX-PAD). Despite improvements in medical care and revascularization, patients with CLI continue to have a high risk of major amputation (below the knee or higher) and cardiovascular death (1-year amputation-free survival <60%; 10-year mortality 70%). CLI has a strong social impact and its incidence is rising worldwide, including in Europe. The prevalence of CLI in the population aged 6090 years is estimated as 1% (0.51.2%) with male to female ratio around 3:1. We will evaluate the efficacy, tolerability and safety of multiple intramuscular injections of HLA-unmatched allogeneic PLX-PAD for the treatment of CLI patients who are unsuitable for revascularization, in a randomized, double-blind, multicentre, placebo-controlled, parallel group phase II study. The European Medicine Agency (EMA) accepted PLX-PAD as pilot project for the new Adaptive Pathways to Patients to force timely access for patients to the new therapeutic option. The PACE consortium will go beyond the traditional clinical trial endpoints of safety and efficacy, by state-of-the-art characterizing molecular and functional signature of the PLX-PAD product(s), in depth investigating mechanisms-of-action of PLX-PAD therapy, and exploring biomarkers for understanding response/non-response in particular patients (stratification and therapy response markers). PACE partners are world-leading experts in scalable, clinical grade 3D-cell manufacturing approved by authorities, preclinical and clinical cell therapy, and biomarker analyses with well recognized expertise in designing and performing clinical trials, including those with Advanced Therapy Medicinal Products (ATMPs) integrated with in-patient biomarker and mechanistic side-studies.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.3-2 | Award Amount: 7.90M | Year: 2012

The number of individuals with obesity and type 2 diabetes mellitus (T2DM) is increasing. An alarming aspect is decline in age of onset of T2DM, which is coupled to rise in childhood obesity. Accentuated insulin secretion is observed early in young obese individuals. In many subjects insulin hypersecretion is evident when insulin sensitivity is essentially normal. Based on these observations we propose insulin hypersecretion as an etiological factor promoting lipid deposition, insulin resistance, cellular dysfunction and death in insulin-producing beta-cells and insulin-target brown adipocytes. Pharmacology-based treatment strategies are limited for this growing patient group and the aim of the proposal is to identify novel strategies reducing insulin hypersecretion, which has not been considered a target for intervention in young obese individuals. To address the issue, pediatric obesity clinics and academic centres with focus on beta-cell biology, brown adipocyte imaging, transcript and protein profiling, genetics, epidemiology and bioinfomatics have formed a consortium with two SMEs specialized on biomarker discovery and clinical trials and one large drug company. In the project well-characterized European patient cohorts of more than 3000 obese children will be further characterized with regard to insulin secretion and brown adipocyte mass. Currently used drugs and new principles of intervention based on novel genes, idenitifed in the project and linked with insulin hypersecretion, will be examined for effects on insulin hypersecretion in translational work including the young obese subjects and isolated human islets. Following comprehensive analysis candidate compounds/principles attenuating insulin hypersecretion will be selected, from which novel therapeutic strategies are expected to emerge. Such therapeutic strategies will be of importance for afflicted individuals and European health economy and lead to new opportunities for European industry.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-16-2015 | Award Amount: 5.97M | Year: 2016

Cardiovascular diseases including myocardial infarction (MI), which entails the irreversible loss of heart muscle tissue, constitute a major socio-economic burden in global healthcare. With whole organ transplantation as the only treatment option for end-stage heart failure, MI patients could particularly benefit from advanced cell therapies aimed at the functional reconstitution of damaged hearts. Human induced pluripotent stem cells (hiPSCs) can be derived by reprogramming patients somatic cells. In contrast to adult (stem) cells e.g. from blood, bone marrow or the heart, hiPSCs have unlimited expandability and differentiation potential into all relevant cell types including cardiomyocytes, endothelial cells, pericytes and connective tissue-forming cells, making them highly attractive as a universal cell source for organ repair. However, technologies for the robust therapeutic scale production of hiPSC-derived progenies in line with GMP standards and at reasonable cost are currently lacking. TECHNOBEATs ultimate objectives are 1) to advance therapeutic scale cell production through innovative bioreactor technologies and novel cell monitoring tools, and 2) to develop regulatory compliant bioprocessing of innovative iPSC-based cardiac -tissue. The clinical translation of cardiac -tissue will require 3) the development and application of tools for improved cell delivery and longitudinal in vivo monitoring of cell grafts, and 4) proof-of-concept for safety and functional integration in physiologically relevant preclinical models of cellular heart repair. Through its interdisciplinary excellence, TECHNOBEATs consortium of leading European stem cell researchers, clinicians, tissue-, bioprocess-, and technical- engineers in industry and academia is ideally positioned to address these ambitious objectives. It will provide new treatment options for suffering patients and increase Europes attractiveness as a hub for innovative medical technologies.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.4.2-1 | Award Amount: 7.44M | Year: 2013

Children are often treated as small adultsnot as the special patients they are. Regulations exist to encourage the development of drugs and formulation for children. However, off-patent drugs are often administered to children without appropriate formulations or systematic investigations. Therefore, the paediatric use marketing authorisation (PUMA) has been designed. The EMA Paediatric Working Party has prioritized the unmet need for the cardiovascular off-patent drug enalapril in the European paediatric population. Enalapril is an ACE inhibitor commonly used for cardiac failure in children under 1 year of age, although it is not labelled for any condition in patients <20 kg in European countries. Current problems with the use of enalapril in children include: no appropriate formulation and insufficient stability of the liquid soluble formulation for young paediatric patients; insufficient paediatric pharmacokinetic (PK) data for any formulation; insufficient safety data in neonates, infants, and young children; and limited pharmacodynamics (PD) and efficacy data for paediatric cardiological indications. The aim of the LENA (Labeling of Enalapril from Neonates up to Adolescents) project is to address these shortcomings and provide a basis for a future PUMA of enalapril by developing an age-appropriate solid oral formulation suitable for all paediatric subsets; generating PK and PD data; collecting data on the safety of enalapril in young paediatric patients; and providing dose recommendations based on PK/PD modelling and bridging from adult data. The international collaboration of the LENA investigators will provide the required expertise to develop and evaluate drug formulation, investigate dosing, and recruit paediatric patients for clinical trials while respecting current legislation, regulatory considerations, and ethical aspects, with the aim of applying for a PUMA.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-11-2016-2017 | Award Amount: 6.62M | Year: 2017

Stress Urinary Incontinence (SUI) is a disease affecting over 200 million people worldwide. It represents a condition with a prevalence of 20-50% in women, thereby creating an immense socio-economic burden. The currently available treatment strategies entail various complications and offer only short-term relief to the patients. Tissue engineering using autologous cells offers a feasible alternative for functional restoration of the damaged urinary sphincter muscle and represents an ideal treatment option that could reverse the underlying pathologic conditions. MUSIC aims at translating basic knowledge on regenerative medicine (RM) and stem cell therapy into the clinic by undertaking a first-in-man multisystem study using autologous muscle precursor cells (MPCs) in a combination with neuromuscular electromagnetic stimulation (NMES) in 40 female patients. We will carry out the specific tasks to prove safety and efficacy of the proposed novel multilevel treatment as well as reproducibility of the therapeutic effect. Additional objectives are optimization of the advanced-therapy medicinal product (ATMP) towards totally xeno-free and facilitated manufacturing as well as the introduction of a novel injection technique for more efficient and precise implantation of the final product. Combining expertise, MUSIC features a unique infrastructure, including the knowledge of experts in the fields of RM, urology, cellular biology and biomaterials throughout Europe (CH, NL, UK, A, D). The MUSIC consortium has an exclusive opportunity to determine the validity of this MPC cellular treatment in combination with NMES and to further improve its feasibility and clinical efficacy. The ultimate goal is to significantly improve the patients` quality of life and to exploit a future commercial opportunity by expanding the know-how to various smaller RM centers and companies within Europe, thus, making personalized medicine using autologous cells a more feasible SUI treatment option.

Trinka E.,Paracelsus Medical University
Epilepsia | Year: 2011

Current standard treatment of established status epilepticus after failure of benzodiazepines is intravenous phenytoin/fosphenytoin, phenobarbital, or valproate. Since 2006 two new antiseizure drugs have become available as intravenous formulation: levetiracetam (2006) and lacosamide (2008). Both drugs have been taken up very rapidly by the clinicians to treat acute seizures and status epilepticus, despite lack of evidence from randomized controlled trials. The favorable pharmacokinetic profile and the good tolerability, especially the lack of sedating effects of both drugs make them promising potential alternatives to the standard antiseizure drugs. Future randomized controlled trials are needed to inform clinicians better about the best choice of treatment in established status epilepticus. The experimental evidence as well as the current clinical experience with levetiracetam and lacosamide are summarized in this review. © Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Tauber M.,Paracelsus Medical University
Archives of Orthopaedic and Trauma Surgery | Year: 2013

Acromioclavicular joint (ACJ) injuries represent a common injury to the shoulder girdle. In the management algorithm of acute ACJ injuries complete radiological evaluation represents the key to a successful therapy. According to the classification of Rockwood the presence of a horizontal component in addition to vertical instability has to be detected. Using axillary functional views or Alexander views dynamic horizontal ACJ instability can be diagnosed in a simple, efficient and cost-effective manner reducing the number of mis-/underdiagnosed ACJ injuries. MRI should not be the imaging modality of first choice. The treatment of ACJ dislocations must consider two aspects. In addition to the correct type of injury therapy strategies should be adapted to patient's demands and compliance. Low grade AC injuries types I and II are treated non-operatively in terms of skilful-neglect. High-grade injuries types IV-VI should be treated operatively within a time frame of 2-3 weeks after injury. A certain debate is still ongoing regarding type III injuries. Out from the literature, non-operative treatment of type III injuries results to provide at least equal functional outcomes as compared to surgical treatment associated with less complications and earlier return to professional and sports activities. If surgical treatment is indicated, open surgical procedures using pins, PDS-slings or hook plates are still widely used concurring with recently raising minimally invasive, arthroscopic techniques using new implants designed to remain in situ. Combined coracoclavicular and acromioclavicular repair are gaining in importance to restore horizontal as well as vertical ACJ stability. © 2013 Springer-Verlag Berlin Heidelberg.

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