Global Impact: Phil Durham

Phil Durham, Biochemist
RTI International

PD HeadshotTuberculosis (TB) is responsible for more than 1.8 million deaths each year, according to the World Health Organization, yet there has been little significant improvement in therapies in the past 20 years. This chronic disease is systemic, meaning it affects not only the lungs but also other organs, such as the lymph nodes and spleen. But a promising new treatment may be on the horizon.

The relatively slow rate with which we identify and develop new antibiotics can be mitigated by pairing novel drug delivery strategies with existing molecules. Tuberculosis presents an interesting opportunity for pulmonary drug delivery, as the lungs are the predominant site of infection and symptoms manifestation. Local delivery allows us to circumvent certain bioavailability and distribution hurdles.

By changing the delivery route, we were able to show (a) a comparable level of efficacy as orally delivered pyrazinamide PZA while (b) using a metabolite (POA) that is potentially effective against PZA-resistant organisms (c) at an estimated fraction of the dose the oral route requires. The efficacious potential of POA has been debated for decades, with supporting evidence for and against efficacy in vitro (comparative to PZA), but when tested in vivo it has historically not been effective.

Since the 2016 AAPS Annual Meeting and Exposition, we’ve submitted a grant to further this work with a collaborator I met there. AAPS has been very accommodating. It was both my first press release and my first interview, and it was very smooth and easy. The response has been great, and a number of people have asked me about our work both at the conference and continuing. [past efforts haven’t] generated the same level of interest as this has with the help of AAPS.

Treating tuberculosis via lungs shows potential

Administering epurposed drug to treat TB given via lungs vs orally