After a 30-year void that saw no significant advances in antituberculosis drug development, scientists report the successful preliminary testing of a set of compounds that act via a completely new mechanism.
These compounds, the nitroimidazopyrans, are structurally similar to the antibiotic metronidazole. According to Kendall Stover (PathoGenesis Corporation, Seattle, WA, USA) and colleagues, who developed the drugs, the lead compound, PA-824, is bactericidal against Mycobacterium tuberculosis (including multidrugresistant strains), is highly specific for the M tuberculosis complex, and, unlike current antituberculosis drugs, is active against growing and static organisms alike. Experiments in mice and guinea pigs showed that orally administered PA-824 was as effective as similar doses of isoniazid (Nature 2000; 405: 962-66).
Despite being excited by the new development, Stephen Gillespie (Royal Free and University College Medical School, London, UK) warns that there are many obstacles to overcome before the compound can be introduced into clinical practice. Not least of these is the reluctance of some drug companies to pursue the development of antituberculosis drugs because of their poor perceived profitability. "Clinical trials could theoretically go ahead within the time-frame recommended by the Global Alliance for TB Drug Development", says Stover, "but whether they're done by us or by someone else depends on funding. We're currently trying to figure out ways to go forward, maybe through licensing or collaborations".
Gillespie predicts that if such ways can be found, "the nitroimidazopyrans, alongside the oxazolidinones and new quinolones, give some reason for optimism for the future".