NATT

New Approaches to Target Tuberculosis

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 Obiettivo del progetto (Objective)

'The increasing emergence of multidrug resistant strains and extensively drug resistant strains, the last one being virtually untreatable, urgently demand novel drugs for therapy of tuberculosis. This project has the aim of bringing together a number of research scientists with expertise in a broad range of disciplines, both from Europe and from India, covering the development field from chemistry to in vivo evaluation. The selected targets belong to either the group of targets from which some proof of concept already exist (mycolic acid synthesis and ATP synthase) either to the group of completely new targets that will be validated (thymidylate synthase, acyl-CoA carboxylase, DNA helicases). One alternative strategy to target the host cellular machinery to enhance bacterial killing is, likewise, included. The selected targets are covering fatty acid metabolism, nucleoside synthesis, energy generator, the survival of the microorganism in macrophages, the nucleic acids metabolism. The systems selected include those from which we expect to generate compounds active against replicating mycobacteria or to obtain compounds targeting latent infection. The application is divided in four scientific workpackages, including target validation, the interaction with the host cellular machinery, the design and synthesis of new inhibition and in vitro and in vivo screening of drug candidates and one management workpackage. A considerable part of the drug development and assessment against drug resistant Mycobacterium tuberculosis will be carried out by the Indian partners, one of which is an SME.'

Introduzione (Teaser)

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is no longer a disease of the past. It has reappeared as a threat with the emergence of multi-drug-resistant and extensively drug-resistant strains.

Descrizione progetto (Article)

There is an urgent demand for innovative new drugs to combat tuberculosis (TB) cause by Mycobacterium tuberculosis (Mtb). The rapid emergence of strains characterised as multi-drug resistant (MDR) and extensively drug resistant (XDR) is further intensified by a dangerous connection with the human immunodeficiency virus (HIV).

The 'New approaches to target tuberculosis' (NATT) project, bringing together research scientists from Europe and India, aims to develop drug candidates able to take on forms of TB that are either latent or active. The latter will include MDR and XDR strains. With expertise covering the development field from chemistry to in vivo evaluation, the consortium will develop novel inhibitors targeting unexplored as well as validated Mtb and host cell proteins.

The project spans four scientific work packages. These cover target validation, interaction with the host cellular machinery, design and synthesis of new inhibition and in vitro and in vivo screening of drug candidates, and a management work package. Two approaches were implemented during the first 18 months of this three-year project. The first focused on the bacterial machinery involved, while the second targeted the host cellular machinery to enhance bacterial killing.

The Indian partners, one of which is a small to medium-sized enterprise (SME), have taken on a major part of the drug development and assessment against drug-resistant Mtb.