Remembering the Host in Tuberculosis Drug Development

Daniel J Frank; David J Horne; Noton K Dutta; Moagi Tube Shaku; Rajhmun Madensein; Thomas R Hawn; Adrie J C Steyn; Petros C Karakousis; Bavesh Davandra Kana; Graeme Meintjes; Barbara Laughon; Zaid Tanvir

doi:10.1093/infdis/jiy712

Remembering the Host in Tuberculosis Drug Development

J Infect Dis. 2019 Apr 19;219(10):1518-1524. doi: 10.1093/infdis/jiy712.

Authors

Daniel J Frank¹, David J Horne², Noton K Dutta³, Moagi Tube Shaku⁴, Rajhmun Madensein⁵, Thomas R Hawn², Adrie J C Steyn^{6

7}, Petros C Karakousis³, Bavesh Davandra Kana^{4

8}, Graeme Meintjes^{9

10}, Barbara Laughon^{11

12}, Zaid Tanvir^{12

13}

Affiliations

¹ Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
² University of Washington School of Medicine, Seattle.
³ Center for Tuberculosis Research and Center for Systems Approaches to Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁴ DST/NRF Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa.
⁵ Inkosi Albert Luthuli Central Hospital and University of KwaZulu-Natal, Durban, South Africa.
⁶ Department of Microbiology, University of Alabama at Birmingham, Durban, KwaZulu Natal, South Africa.
⁷ Africa Health Research Institute, Durban, KwaZulu Natal, South Africa.
⁸ MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Centre for the AIDS Programme of Research in South Africa, CAPRISA, Durban, South Africa.
⁹ Wellcome Centre for Infectious Diseases Research in Africa, Cape Town, South Africa.
¹⁰ Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa.
¹¹ Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
¹² Stop TB Partnership Working Group on New Drugs, New York, New York.
¹³ Global Alliance for TB Drug Development, New York, New York.

Abstract

New therapeutics to augment current approaches and shorten treatment duration are of critical importance for combating tuberculosis (TB), especially those with novel mechanisms of action to counter the emergence of drug-resistant TB. Host-directed therapy (HDT) offers a novel strategy with mechanisms that include activating immune defense mechanisms or ameliorating tissue damage. These and related concepts will be discussed along with issues that emerged from the workshop organized by the Stop TB Working Group on New Drugs, held at the Gordon Research Conference for Tuberculosis Drug Development in Lucca, Italy in June 2017, titled "Strategic Discussion on Repurposing Drugs & Host Directed Therapies for TB." In this review, we will highlight recent data regarding drugs, pathways, and concepts that are important for successful development of HDTs for TB.

Keywords: drug development; host-directed therapy; macrophage; meningitis; tuberculosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Antitubercular Agents / pharmacology
Antitubercular Agents / therapeutic use*
Drug Development / methods*
Humans
Mycobacterium tuberculosis / drug effects
Tuberculosis / drug therapy*
Tuberculosis / immunology
Tuberculosis, Multidrug-Resistant / drug therapy
Tuberculosis, Multidrug-Resistant / immunology

Substances

Antitubercular Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding