Objective
The general aim is to detect, understand, predict and avoid drug hepatotoxicity:
Clinical studies will be undertaken to elucidate clinical, environmental and pharmacogenetic risk factors and to determine whether modulation of drug bioactivation/detoxication in patients in vivo influences their susceptibility
Mechanistic investigations will be used to investigate pathways of drug bioactivation and toxicity, and to define cellular and immunoallergic mechanisms of drug toxicity.
Drug hepatotoxicity is a major clinical and socio-economic problem in the E.C. This is because hepatotoxicity is among the most frequent of the organ toxicities caused by drugs and because drug-induced hepatotoxicity may lead to chronic disease, death or liver transplantation. Although hundreds of hepatotoxic drugs have now been identified, in only a few cases have the mechanisms of toxicity been defined. In consequence, little is known concerning the reasons why some patients are susceptible to the hepatotoxicities, but many other patients are not. Furthermore, model systems which can be used to predict and study the toxicities are not available. In view of this, a multidisciplinary and multinational European research network (EUROHEPATOX) will be established and a strategy will be adopted which will make possible integrated clinical, molecular and cellular studies of mechanisms of drug hepatotoxicity.
Clinical studies:
Detection of patients with drug hepatotoxicity via prospective/retrospective trials
Investigation of clinical, environmental and pharmacogenetic risk factors
effects of modulating bioactivation/bioinactivation on patients' susceptibility
Drug bioactivation and bioinactivation
Identification of metabolic and genetic risk factors and chemoprotective factors
Development and validation of novel in vitro techniques
Cellular mechanisms of drug hepatotoxicity
Apoptosis, mitochondrial toxicity, oxidative stress
Interrelationships with metabolic and genetic factors affecting bioactivation
Immunoallergic mechanisms of drug hepatotoxicity
Identification and characterization of hepatic protein adducts
Interrelationships between adduct expression and drug bioactivation
Antibody and T cell response to the adducts in patients
In vitro models of immunoallergic drug hepatotoxicity.
This general strategy will be used to investigate four groups of themed drugs, which have been chosen for study because they are important and widely prescribed and because the toxicities observed in patients treated with these drugs differ markedly with respect to incidence and patterns of liver injury. These are the nonsteroidal antiinflammatory drugs (NSAIDs), penicillins, tacrine (which recently has been introduced for treatment of Alzheimer's disease) and the anti-cancer drugs. The objective is to develop techniques and approaches (particularly in vitro methodologies) which will make possible: safer and more effective use of existing drugs
development and evaluation of new and less toxic drugs.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences clinical medicine transplantation
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
W2 1PG London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.