Service Communautaire d'Information sur la Recherche et le Développement - CORDIS


GENDEP Résumé de rapport

Project ID: 503428
Financé au titre de: FP6-LIFESCIHEALTH
Pays: United Kingdom

Final Report Summary - GENDEP (Genome-based therapeutic drugs for depression)

One in five people at some point in their lives suffer from an episode of depression severe enough to warrant antidepressant treatment. Although, currently there is plenty of evidence for efficacy of antidepressants, a substantial minority of patients show an unsatisfactory response to medication, and cessation of taking prescriptions is common because of adverse side-effects. At present doctors do not have enough information to know how well patients will respond to one antidepressant over another. The choice of what drug to prescribe for optimal response with minimum unwanted effects is largely a matter of taking an educated guess. It was hoped that the GENDEP project will lead to the development of a genetic test to assist doctors in choosing the right antidepressants for their patients and that it will advance understanding of the biological mechanisms responsible for an antidepressant being effective, which is important for the development of new and better treatments for depression.

GENDEP had three closely interconnected major themes aimed to address these issues. The first is a large-scale multi-centre human pharmacogenomics study focused on the prediction of therapeutic response to antidepressants and adverse effects. The second is a set of basic science studies using animal models and in vitro experiments, and the third is a programme of work to address the relevant ethical, social, and legal issues.

The expected final outcome of GENDEP is to generate information regarding appropriate markers for bioassays applicable to medical services for the prediction of response to antidepressants (including adverse effect profile), which, if subjected to a further prospective evaluation, could result in validated clinical pharmacogenomics assays. These would enable clinicians to make pharmaco-genomically informed choices regarding which type of antidepressant might be most efficacious and be associated with minimal adverse effects.

The project also expects to provide data on the functional characterisation of the molecular mechanisms involved in the effects of antidepressant treatment, leading not only to therapeutic assays applicable to the psychiatric service, but also potentially to diagnostic assays, and the prediction of novel therapeutic targets. The achievement of these objectives would represent highly significant advances in preclinical and clinical psychopharmacology, and psychiatric therapeutics, potentially revolutionising the management of depression.

The development of effective, targeted treatments for what is currently a major societal problem could have significant economic and health impacts across Europe. Successful pharmaco-genomic research on a common complex disorder such as depression, leading to better differential diagnosis and choice of treatment is also likely to set the path for similar research on other common complex disorders.

The project enables European SMEs to work in a collaborative and integrated fashion with leading academic centres and a large industrial partner. The multicentre pan-European collaborative nature of this research project includes unique mobilisation of resources and expertise across Europe, in an integrated project that has the power to generate data of high scientific import and to enable sustained pan-European research in this field to be conducted in a manner that will be truly competitive in the international arena.

The exploitable knowledge created includes know-how about how to conduct a large-scale multicentre human pharmacogenomics study, knowledge of biomarkers associated with clinical response to antidepressants in various model systems and the human pharmacogenomics study, and drug-able targets for pharmaceutical drug discovery. Patents will be sought at the appropriate time, with commercialisation to be undertaken either by relevant CRs in the consortium or other industrial partners.

Several presentations have already been made at conferences and published in abstract form. An editorial has also been written in the British Journal of Psychiatry (2005; 286: 91-92). CR1 and CR9 have had contact with the media in their countries, including GENDEP being featured on Channel 4 News (24 July 2004), and an article in Nature News and Views (2004; 428: 791). Work is in progress to create a public website. Reports to various key stakeholders will be delivered, and data submitted to other websites (e.g. genetic or pharmaco-genetic websites) as appropriate.

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United Kingdom