Descrizione del progetto
Antibiotici più sicuri contro la resistenza antimicrobica
Le polimixine sono una famiglia di antibiotici per il trattamento e la gestione di batteri farmacoresistenti, tra cui lo Pseudomonas aeruginosa. Nonostante la loro tossicità epatica, la loro prescrizione è ripresa negli ultimi anni per affrontare la resistenza antimicrobica. Il progetto NOVA, finanziato dal Consiglio europeo della ricerca, propone di sviluppare polimixine semi-sintetiche con una tossicità intrinseca ridotta, ma con un’efficacia superiore contro i batteri multifarmaco-resistenti. L’idea è migliorare la sicurezza dei pazienti e concorrere alla lotta contro la resistenza antimicrobica. L’approccio semi-sintetico di NOVA assicura una produzione a basso costo di una serie di analoghi di polimixine. È importante sottolineare che gli antibiotici selezionati saranno sperimentati per il loro potenziale di indurre la resistenza.
Obiettivo
In the NOVA ERC PoC project, we present a novel class of semi-synthetic polymyxins as an innovative solution to address the inherent toxicity of the polymyxins family of antibiotics. We here disclose the first candidate compounds of this novel family of antibiotics with potential for use as front-line treatment for multi-drug-resistant Gram-negative bacterial infections.
Due to antimicrobial resistance (AMR), a resurgence in the use of polymyxin antibiotics has occurred over the last decade, despite the well characterised and dose-limiting nephrotoxicity associated with these compounds. Though designated as last-resort antibiotics due to these side effects, the ongoing rise of AMR is forcing clinicians to rely on unsafe antibiotics such as the polymyxins. Increased polymyxin use results in risks for patients and pressure on healthcare systems.
Our novel semi-synthetic polymyxins have best-in-class potential given their significantly improved safety profile and offer a superior alternative to current last-resort anti-Gram-negative antibiotics. Succinctly, the next generation polymyxins we have developed offer key advantages over current last-resort antibiotics: (i) reduced nephrotoxic side effects, (ii) effectiveness against multi-resistant strains with negligible resistance induction, and (iii) ability to be produced at low cost. Moreover, our robust semisynthetic approach will allow us to generate additional analogues in the future.
In NOVA, we will explore the technical and commercial potential of our next generation polymyxins. Specifically, we will validate the first candidate compounds and perform preliminary preclinical toxicity studies in vivo. In parallel, we will evaluate the commercial feasibility of the next generation polymyxins. This entails analysing the market and (existing and emerging) competitors, as well as the IP position and strategy. By the end of the project, we will consolidate the project outcomes in an investor-ready business plan.
Campo scientifico
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-AG-LS - HORIZON Lump Sum GrantIstituzione ospitante
2311 EZ Leiden
Paesi Bassi