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WIEN, Austria

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.5-2 | Award Amount: 7.86M | Year: 2010

Chronic inflammatory diseases associated with allergy, including asthma and rhinitis, constitute a major and continuously growing public health concern for Europe. However, the causative factors and mechanisms converting a physiological inflammatory reaction to a chronic response triggering allergic disease remain elusive. Viral infections, particularly those caused by human rhinoviruses (RV) are the most frequent triggers of acute asthma exacerbations. RV infections have more recently been associated with asthma initiation; there is evidence suggesting that such infections may also contribute to respiratory allergy persistence. The strategic aims of PreDicta are to evaluate the hypothesis that repeated infections reprogram the immune system towards a persistent inflammatory pattern leading to respiratory allergies by (i) dissecting the molecular and cellular mechanisms involved in the lack of resolution of inflammation in the context of a human disease, (ii) identifying specific infectious agents and underlying altered host-pathogen interactions, and develop relevant prognostic and therapeutic strategies. PreDicta follows three interconnected workflows: models, mechanisms and translational output. Models include a longitudinal cohort in children, mouse models of repeated virus infection, primary epithelial cultures from patients, viral-bacterial interaction models, and models of epithelial-T-cell-dendritic cell interactions. These will be used to look into disease persistence, inflammation patterns, dysbiosis, immune regulation and resolution of inflammation. Translational outputs include prognostic use of subtype-specific antiviral antibodies, DNAZymes for therapeutic use and delivery technologies targeted to the bronchial epithelium. This interdisciplinary Consortium with strong track record, unique resources and strong translational focus, aims to produce new knowledge and technologies that can rapidly and effectively reach clinical care.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.3-3 | Award Amount: 9.59M | Year: 2014

Allergy is the most prevalent chronic inflammatory disease, having great socio-economic impact. Chronic lifelong dependency on symptomatic drugs is an expensive reality for the vast majority of allergy sufferers. Allergen-specific immunotherapy is the only causal and effective treatment targeting the underlying immune mechanism in a more cost-effective way. Yet, long treatment duration and risk of anaphylactic side-effects have prevented this treatment from becoming the first choice. BM4SIT aims at providing an escape from its current niche position by making the treatment safer, more effective and patient friendlier, i.e. developing a therapy with negligible side-effects but improved efficacy, achieved by less injections. The concept of BM4SIT is based on two innovations: replacing current natural allergen extracts by mutated recombinant allergens having been designed to be hypo-allergenic but hyper-immunogenic, and adding an adjuvant to support rapid and effective induction of an anti-inflammatory immune response. The allergen derivative chosen to bring this concept from bench to bedside is BM4, a mutant of the culprit allergen of birch pollen allergy, Bet v 1. Pre-clinical data have demonstrated strongly reduced allergenicity, significantly increased immunogenicity and efficacy in a mouse model for birch pollen allergy. The selected adjuvant is vitamin D3, which has been shown to promote active suppression of inflammation, both in vitro and in a mouse model. The product-focused, IP-protected consortium of BM4SIT will bring BM4 and vitamin D3 to the start of Phase III clinical trials via the stages of GMP production, toxicity studies, and Phase I and II clinical trials. Addition of vitamin D3 will first be evaluated against placebo and a current product, followed by a safety and dose-range-finding study using BM4 and vitamin D3. BM4SIT will pave the way towards a better more attractive therapy that will improve the cost-benefit ratio compared to symptomatic drugs.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.4.5-1 | Award Amount: 15.66M | Year: 2010

Causes explaining the epidemic of IgE-associated (allergic) diseases are unclear. MeDALL (Mechanisms of the Development of Allergy) aims at generating novel knowledge on mechanisms of allergy initiation, in particular in childhood. To understand how a complex network of genetic and environmental factors leads to complex allergic phenotypes, a novel stepwise, large and integrative translational approach is needed. MeDALL includes experts in allergy, epidemiology, genetics, immunology, biology, animal models, biochemistry and systems biology combining strengths of ongoing EU projects. Classical phenotypes (expert-based) and novel phenotypes of allergy (hypothesis-free statistical modelling) are compared. Population-based data are collected from a cross-sectional study (Karelia) and existing birth-cohorts followed using a common protocol. IgE to foods and inhalants are tested using component-resolved diagnosis across Europe in populations. Biomarker profiles (fingerprints) are extensively assessed using epigenetics, targeted proteomics and unbiased transcriptomics in a subsample of the study population. Those associated with allergic phenotypes are validated in large study populations. Relevant fingerprints are combined into network biomarker phenotype handprints using a systems biology approach and validated in a sufficiently powered sample. Animal studies and in vitro human immunology reinforce the validation. This information coupled with classical and novel phenotypes characterize environmental protective and susceptibility factors of allergy and risk groups. Results are fitted into new integrative complex mathematical models to establish suitable biomarkers for early diagnosis, prevention and targets for therapy of allergy-associated diseases such as asthma and atopic dermatitis. Ethics and gender are considered. MeDALL aims at improving health of European citizens, Europe competitiveness and innovative capacity while addressing global health issues.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-1.4-3 | Award Amount: 4.16M | Year: 2008

The FAST project aims at the development of safe and effective treatment of food allergies. It targets persistent and severe allergy to fish and fruit. Besides persistence and severity, this choice is based on prevalence and the importance of these foods for a healthy diet. Classical allergen-specific immunotherapy (SIT) for treatment of food allergy using subcutaneous injections with food extracts has proven to be effective but too dangerous due to anaphylactic side-effects. FAST will therefore develop a safe alternative by replacing food extracts with hypo-allergenic recombinant major allergens, the active ingredients of SIT. Both severe fish and fruit allergy are caused by a single major allergen, parvalbumin for fish and lipid transfer protein for fruit. This makes development of a novel biotechnological product feasible. Two approaches will be evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypo-allergenic versions of parvalbumin and lipid transfer protein will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), Phase I and II randomized double-blind placebo-controlled multi-center clinical trials will be performed. Two routes of administration will be evaluated, subcutaneous in case of fish and sublingual in case of fruit. The primary read-out will be the double-blind placebo-controlled food challenge. To understand the underlying immune mechanisms of subcutaneous and sublingual immunotherapy, these trials will be accompanied by in depth serological and cellular immune analyses, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST will improve the quality of life of food allergic patients by providing a safe and effective curative treatment that will end their dependence on avoidance and rescue medication.

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