A novel anti-infective approach is being utilized to exploit stresses already imposed on invading organisms in vivo. Iron (Fe) metabolism is a key vulnerability of infecting bacteria because organisms require Fe for growth. Studies may indicate that possibly a """"""""Trojan horse"""""""" strategy that uses the metal gallium (Ga) to disrupt bacterial Fe metabolism holds promise as an antimicrobial approach. Due to its chemical similarity to Fe, Ga can substitute for Fe in many biologic systems and inhibit Fe-dependent processes. Data may show that Ga kills the opportunistic pathogen Pseudomonas aeruginosa (including antibiotic resistant strains), may be active against biofilms, and may treat three different model P. aeruginosa infections. Ga may be a promising new therapeutic for P. aeruginosa infections. A pharmacokinetic and safety study of intravenous (IV) Ga in subjects with cystic fibrosis (CF) is being proposed as chronic P. aeruginosa airway infections are the major cause of death in these patients and few treatments exist.
Our data shows that gallium (Ga) kills the opportunistic pathogen Pseudomonas aeruginosa (including antibiotic resistant strains), is active against biofilms, and treats 3 different model P. aeruginosa infections. P. aeruginosa accounts for approximately 60% of the chronic lung infections in patients with cystic fibrosis (CF), an orphan disease, and ~ 90% of deaths are attributed to chronic airway damage caused by this organism. We propose to assess safety, tolerability and pharmacokinetics in this patient population. We will also evaluate preliminary clinical efficacy measures - lung function, sputum microbiology and respiratory symptoms. If this is successful, this approach could provide a novel agent to fight chronic infections with P. aeruginosa in other disease settings beyond CF.
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