Developing new antimicrobials for the treatment of tuberculosis and mycetoma through open source drug discovery

Abstract

Diseases that predominantly affect people in poorer nations have been historically neglected by the profit-motivated pharmaceutical industry. Tuberculosis (TB) and mycetoma are two examples of such diseases. Despite being the most fatal infectious disease globally, there has been relatively little innovation in the treatment of TB in the past four decades, and drug-resistant strains of TB are becoming an increasing concern. Mycetoma is a condition caused by either bacteria (actinomycetoma) or fungi (eumycetoma), resulting in tumour-like growths that disfigure and disable those affected. Actinomycetoma is currently treated with a harsh and lengthy drug regime which increases the likelihood of patient non-compliance, leading to the bacteria developing resistance to the antibiotics in use. Meanwhile, the curative rate of antifungals used against eumycetoma is estimated to be as low as 25%, even with treatment also including surgical intervention.

Open source drug discovery (OSDD) is a research model that aims to accelerate the development of new treatments for neglected diseases by following the principles of open science, which include sharing data openly and encouraging collaboration at all levels. This thesis describes the progress of two OSDD projects in mycetoma and TB research.