The Tuberculosis Drug Accelerator at year 10: what have we learned?
July 5, 2021
Bree B. Aldridge, David Barros-Aguirre, et al
Nat Med. 2021 Jul 5. doi: 10.1038/s41591-021-01442-2. Online ahead of print.
PMID: 34226736 | DOI: 10.1038/s41591-021-01442-2
The Tuberculosis Drug Accelerator, an experiment designed to facilitate collaboration in tuberculosis drug discovery by breaking down barriers among competing labs and institutions, has reached a 10-year landmark. We review the consortium’s achievements, advantages and limitations and advocate for the application of similar models to other diseases.
Tuberculosis (TB) claimed 1.4 million lives in 2019, which ranks it among the leading causes of death and one of the most lethal diseases caused by a single infectious agent. That year, 10 million people fell ill with TB, 2% of whom had multidrug-resistant disease. As the cornerstone of TB control, ‘short-course’ combination chemotherapy has two inter-related limitations: its 6-month duration, which reduces adherence; and its diminishing efficacy, which reflects the emergence and spread of drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mtb). Encouragingly, recently developed regimens comprising new and repurposed drugs simplify and shorten the treatment of multidrug-resistant TB1. However, the main objective in TB chemotherapy is to develop dramatically shortened, less toxic, universal drug regimens that can achieve rapid, durable cure irrespective of resistance to existing drugs.
This goal underpinned the formation of the TB Drug Accelerator (TBDA), an innovative multi-sector, multi-partner, multi-disciplinary, virtual collaborative network. In addition to fueling the TB drug pipeline with new targets, leads, clinical candidates and regimens, the TBDA has enabled technological advances of broad relevance to anti-infective drug discovery and regimen design. Here we review the first decade of the TBDA, highlight some of its achievements, and reflect on how the learnings from this experiment might inform approaches to drug discovery for other diseases.