OpenSourceTB:Story so far
Open Source TB was started in 2014 through a partnership between Matthew Todd at The University of Sydney and GlaxoSmithKline Tres Cantos, funded by the OpenLab Foundation. This initial project examined the first three OSTB Series. The initial grant, which finished in August 2015, created the online platform of this wiki, the Landing Page, the GitHub platform and the Twitter account. These are free to use by anyone, and people are encouraged to use the OSTB online presence to help run their own projects.
General Background to TB
The TB Alliance and the Working Group on New TB Drugs host pages detailing the current pipeline in discovery (1, 2) and development (1, 2) phases. Few new drugs have been approved in recent decades.Cole 2013 Review (10.1038/nrd4001); 2015 review ERJ Open Res (10.1183/23120541.00010-2015)
Antimicrobial resistance is a major and growing problem.WHO Report There are calls for more global efforts to address the problem Farrar Nature Article 2014, 10.1038/509555a Lancet Infectious Diseases 2013, 10.1016/S1473-3099(13)70318-9 Lancet 2016 2016 Science Global Targets and exploration of research models "driven by public need rather than market forces", 10.1038/509533a as well as debate about new financial models (Lancet 2016) that might stimulate greater R&D activity. Lancet 2017 piece on antibiotic research priorities. Bulletin of WHO on 3P Initiative Pull Incentives 2017, Mix of methods including market entry awards
Tuberculosis is a major public health problem, with one-third of the world's population infected with the causative agent, Mycobacterium tuberculosis, resulting in 9 million cases of clinical TB and 1.3 million deaths.2015 WHO TB report Lancet Editorial 2015, 10.1016/S1473-3099(15)00431-4, Ann Intern Med. 2015, 10.7326/M14-2210
The incidence of TB worldwide is worsened by the current HIV/AIDS pandemic because ...
There are multi-drug resistant strains (MDR-TB) and now strains that are resistant to all known treatments.2014 review, 10.7861/clinmedicine.14-3-279, Lancet Resp Med 2014, 10.1016/S2213-2600(14)70031-1 Worryingly it seems possible for such resistance not to incur fitness costs.2014 Nature Rev Micro, 10.1038/nrmicro3225
There is a pressing need for new small molecule drugs to treat this disease. Initiatives along these lines include the screening of the compound libraries of pharmaceutical companies,Novartis/Pasteur 2013 Nature Med Q203 such as those performed by GlaxoSmithKline from which the data were released into the public domain.2015 PLoS ONE, 10.1371/journal.pone.0142293ChemMedChem 2013 10.1002/cmdc.201200428 Alongside the need for new compounds is a requirement for improved access to drugs, in particular to limit the spread of resistant strains.WHO policy paper 2015
The End TB Strategy was adopted by the World Health Assembly in May 2014. This aims to reduce TB deaths by 90% between 2015 and 2030, and reduce new cases by 80%. The resolutions of the strategy include #72 to "Develop new drugs and regimens for the treatment of all forms of tuberculosis" and #73 to "Enhance research to detect and treat latent infection...These strategies should include new medicines". The Obama Administration in the United States in December 2015 released a National Action Plan for combating MDR-TB.
An important strategy is to target "non-replicating" or "latent" tuberculosis. A small number of candidate compounds are known to be effective.Rv2466c (10.1021/cb500149m); oxazolidinones (10.1128/AAC.02410-14)
Beyond tuberculosis there is growing interest in non-TB mycobacterial infections (NTM) in part because there are so few effective therapies.Soni 2015 10.1099/jmm.0.000198