Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.31M | Year: 2012
Chronic liver diseases (CLD) and their end-stages, cirrhosis and hepatocellular carcinoma (HCC), are leading causes of morbidity and mortality worldwide with enormous socio-economic costs. Patients with liver cirrhosis are at high risk of deadly hepatic failure and over 80% of HCC develop on a cirrhotic background. HCC ranks as the 5th most common cancer and with >600,000 deaths per annum it constitutes a major global health problem. The main etiologies of CLD are chronic HCV and HBV infections, alcohol abuse and nonalcoholic steatohepatitis (NASH) as a result of the metabolic syndrome taking epidemic proportions. Liver transplantation is currently the only available therapy for terminal liver failure. It is well recognized that the cytokine TGF-Beta plays a pivotal role in the sequence of events leading to end-stage CLD, but the complexity of the underlying aberrant responses in the cells and the organ that lead to the drastic changes seen in CLD and HCC is poorly understood. A broad spectrum of scientific and technological capacities is needed to accomplish the goal of discovering drugs and treatment modalities for CLD and HCC.As a result, there is a lack in academia and industry alike - of internationally oriented researchers and research leaders, capable of seamless and bi-directional transfer of goal-oriented scientific knowledge and technologies between the basic, translational and clinical research and industrial capacities; a conditio sine qua non for effectively and efficiently combating CLD and HCC and alleviate its medical and socio-economic burdens. Consequently, the ITN formulated the mission to provide a multidisciplinary and intersectorial Research Training Programme for talented young researchers, so as to prepare them for leading roles in CLD research and drug discovery in European industry and academia.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.4-1 | Award Amount: 4.35M | Year: 2011
Acute intermittent porphyria (AIP) is a rare genetic disease in which mutations in the porphobilinogen deaminase (PBGD) gene produce insufficient activity of a protein necessary for heme synthesis. This leads to an accumulation of toxic intermediates resulting in a wide variety of problems including acute, severe abdominal pains, psychiatric and neurological disorders, and muscular weakness. Acute porphyric attacks can be life-threatening and the long-term consequences include irreversible nerve damage, liver cancer and kidney failure. AIP affects 1/10,000 people in the EU and the therapies currently available do not prevent the symptoms or consequences of acute porphyric attacks. The only curative therapy is liver transplantation and thus, new curative options are clearly needed. In 2009, the European Medicines Agency granted Orphan Drug Designation to AAV5-AAT-PBGD for the treatment of AIP. AAV is a replication-incompetent virus that has been modified to deliver genes or genetic material into human tissues or cells. AAV5-AAT-PBGD acts by delivering the PBGD expression cassette directly into hepatocytes. In heterozygous AIP patient that show 50% of the normal activity the additional PBGD activity will be sufficient to prevent the accumulation of toxic metabolites and thus, to prevent porphyric attacks. the aim of this project is the clinical development of the orphan drug AAV-AAT-PBGD for use to treat AIP. The project will be performed in three different phases. In the first phase, we will develop a GMP-compliant process to produce sufficient AAV5-AAT-PBGD for clinical trials, and we will constitute the largest possible cohorts to improve the follow-up of patients and determine the clinical criteria to select patients for gene therapy. In the second phase, the safety and efficacy of AAV5-AAT-PBGD will be explored in a dose escalation clinical phase I/II trial.
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.4.2-4 | Award Amount: 15.96M | Year: 2011
More than 50% of heart failure (HF) patients present without a major deficit of left ventricular (LV) systolic function and are presumed to suffer from diastolic HF (DHF) because diastolic LV distensibility is usually impaired in these patients. The vast majority (~80%) of DHF patients is exposed to metabolic risk factors. The MEDIA consortium therefore investigates:1) how metabolic derangements contribute to DHF; 2) how diagnostic algorithms for DHF can be improved by assessing metabolic risk; 3) how correction of metabolic risk can open new therapeutic perspectives for DHF.Hereto MEDIA will: 1) Expose animal models of DHF to intense metabolic risk in order to accelerate DHF development. 2) Perform mechanistic studies in cardiomyocytes derived from DHF animal models or from DHF patients. Because of the acquired nature of metabolic risk, these studies will focus on posttranslational modifications of proteins and on epigenetic control of hypertrophy development. Their relevance for global LV function will also be appraised; 3) Perform mechanistic studies on myocardial collagen synthesis, which is enhanced by metabolic risk, and execute a phase II trial in DHF with cardiac specific antifibrotic therapy; 4) Explore the use of biomarkers as premorbid identifiers of DHF in existing cohorts of patients exposed to metabolic risk; 5) Prospectively test biomarkers and arterial stiffening, which is accelerated by metabolic risk, for their diagnostic potential in a large DHF cohort; 6) Assess myocardial metabolic substrate preference with modern imaging techniques and improve diastolic LV dysfunction through modified substrate utilization in a phase II trial. Expected results of MEDIA are: 1) Identification of metabolic risk-related mechanisms as therapeutic targets; 2) Improved diagnostic algorithms through inclusion of biomarkers and arterial stiffness tests. 3) Novel treatments consisting of modified myocardial substrate utilization and myocardial antifibrotic therapy.
Digna Biotech and Proyecto De Biomedicina Cima S.L. | Date: 2011-02-21
The invention refers to the use of transforming growth factor-beta 1 (TGF-1) inhibitor peptides or polynucleotides encoding said peptides for the prevention and/or treatment of corneal fibrosis and/or corneal haze.
Digna Biotech | Date: 2011-01-31
A process for producing an interferon alpha 5 (IFNa5) protein by expression in an IFNa5 producing