Research Article: New Approaches to Filling the Gap in Tuberculosis Drug Discovery

Date Published: November 6, 2007

Publisher: Public Library of Science

Author(s): Martina Casenghi, Stewart T Cole, Carl F Nathan

Abstract: For the first time in decades, say the authors, there is a tuberculosis drug pipeline, but the paucity of candidates is still cause for alarm.

Partial Text: Early stage drug discovery is a key bottleneck in the pipeline to find novel drugs for tuberculosis (TB) [1,2]. For diseases that affect people in wealthy countries, pharmaceutical companies actively scout advances in basic research in search of new and potentially lucrative drug targets. For TB, this is not the case: of the 1,556 new chemical entities marketed worldwide between 1975 and 2004, only three were for TB [3]. The general problem of antibiotic research and development (R&D) has been described elsewhere [4,5], but TB is worth singling out: it is the leading cause of death from bacterial infection, it is spread person to person, and it is a particular threat for nosocomial transmission, with a potentially lethal impact on health care workers [6].

Despite some important recent initiatives—most notably those supported by the United States National Institutes of Health, the European Union, and the Bill & Melinda Gates Foundation, and R&D units set up by Novartis, GlaxoSmithKline, AstraZeneca, and Sanofi-Aventis—major limitations remain. It is becoming clear that current funding paradigms and strategic approaches have not led to the increase in drug discovery activities that will be required to respond to the emergency posed by TB.

One possible approach for generating a significant scale-up of TB drug discovery is to improve public sector capacity for running drug discovery programs. Government funding agencies could establish a medicinal chemistry resource center that would work as a core facility offering free lead optimization and ADMET (absorption, distribution, metabolism, excretion, and toxicology) studies in animal models. Such a facility would be directed by scientists with experience in drug discovery, and could also carry out training activities in order to ensure medicinal chemistry expertise in academia.

Ultimately the gaps in TB drug discovery reflect the structural limitations of the current patent system as it is applied to generate incentives for essential medical R&D. To feed and advance the drug and vaccine pipelines for diseases that offer little traditional market incentive will require a mutually reinforcing alignment of three fundamental processes: innovation, incentive, and access.



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