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Beta-lactams for Tuberculosis Treatment

Objective

Tuberculosis (TB) is the most deadly infectious disease worldwide. TB therapy takes 6 months with unpleasant side effects that leads to poor adherence and the development of drug resistance. Patients infected with multi (MDR) or extensively (XDR) drug resistant strains must undergo longer treatments (up to 24 months) associated with even severe side effects and only 30-50% positive treatment outcomes. New treatments are urgently needed.

Beta-lactams (BLMs) are the safest antibiotics in the market with a long track record of clinical use to treat bacterial infections. They were, however, traditionally regarded as ineffective for TB therapy to the point that research was virtually discontinued for the last three decades. A renewed interest recently arose after a report of Phase IIa clinical trial validated the potential of meropenem (a carbapenem). This study was led by Dr. Barros, Head TB unit GlaxoSmithKline (GSK) (the beneficiary of this proposal). In addition, Dr. Ramón-García (the applicant) just identified first-generation cephalosporins (cephems), a subset of the BLM family never pursued for TB therapy, as potential anti-TB agents. Promoting BLM development is the best immediate hope for TB patients that currently have very dim life prospects.

Carbapenems and cephems have different anti-bacterial killing properties, pharmacokinetic (PK) and pharmacodynamics (PD) parameters. These specificities affect therapy design for an optimal clinical outcome. Although promising, it is still unclear how BLMs should be included in new combo therapies (i.e. dosage, duration and frequency of administration) to shorten the duration of TB therapy, prevent relapse and treat M(X)DR-TB.

To answer these questions, I will use time-lapse microscopy linked to mathematical PK/PD modeling, transcriptomic and proteomic studies and clinical microbiology techniques to provide high quality molecular and PK/PD pre-clinical data to inform the design of future BLM TB clinical trials.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-SE - Society and Enterprise panel

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

FUNDACION AGENCIA ARAGONESA PARA LA INVESTIGACION Y EL DESARROLLO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 170 121,60
Address
PASEO MARIA AGUSTIN 36 EDIFICIO PIGNATELLI PTA 30 PL 2
50004 Zaragoza
Spain

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Region
Noreste Aragón Zaragoza
Activity type
Other
Links
Total cost

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.

€ 170 121,60
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