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Towards the prevention of aminoglycoside antibiotic-related deafness

Objective

Aminoglycosides are critically important antimicrobials used in the treatment of life-threatening infections. A major drawback of usage is hearing loss caused by irreversible damage to the inner ear (ototoxicity). Ototoxicity occurs in ~20% of patients and ~100% of patients with the m.1555A>G mitochondrial DNA mutation. The largest EU patient group exposed to aminoglycosides are children in neonatal intensive care and the effect of hearing loss during infancy is particularly profound as it impedes language acquisition. Thus, there is an urgent need to develop safer aminoglycoside antibiotics. Ototoxicity limits usage despite the antibacterial potency and low incidence of drug resistance provided by this class of antibiotics. Economically, the annual EU cost incurred by drug resistant infections amounts to €1.5 billion, and the cost of hearing impairment is estimated to be €78 billion. Moreover, 25,000 EU patients die annually as a result of infections caused by resistant bacteria and 22.5 million suffer from hearing impairment, with 2 million profoundly deaf.

Stanford research recently published in the Journal of Clinical Investigation has shown that it is possible to chemically modify aminoglycosides to diminish ototoxicity while maintaining antibacterial activity. Through a novel collaboration between Stanford and University College London (UCL), the aim of this research is to use a results-guided drug design approach to develop the next generation of safer aminoglycoside antibiotics. For this work, the candidate will have access to 15 novel patented aminoglycoside compounds, crystallography data, murine in vitro and in vitro models of ototoxicity, and a rare biobank of cells from patients with the m.1555A>G mutation. This work will build upon the candidate’s Distinction Masters of Research structural biology experience at Imperial College London, and UCL PhD and recent first-author publication in Human Molecular Genetics related to aminoglycoside ototoxicity.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2015

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Coordinator

UNIVERSITY COLLEGE LONDON
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.

€ 251 857,80
Address
GOWER STREET
WC1E 6BT LONDON
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
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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.

€ 251 857,80

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