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Why Wait? The Case for Treating Tuberculosis with Inhaled Drugs

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Abstract

The discovery of drugs to treat tuberculosis (TB) was a major medical milestone in the twentieth century. However, from the outset, drug resistance was observed. Currently, of the 10 million people that exhibit TB symptoms each year, 450,000 have multidrug or extensively drug resistant (MDR or XDR) TB. While greater understanding of the host and pathogen (Mycobacterium tuberculosis, Mtb) coupled with scientific ingenuity will lead to new drugs and vaccines, in the meantime 4000 people die daily from TB. Thus, efforts to improve existing TB drugs should also be prioritized. Improved efficacy and decreased dose and associated toxicity of existing drugs would translate to greater compliance, life expectancy and quality of life of Mtb infected individuals. One potential strategy to improve existing drugs is to deliver them by inhalation as aerosols to the lung, the primary site of Mtb infection. Inhaled drugs are used for other pulmonary diseases, but they have yet to be utilized for TB. Inhaled therapies for TB represent an untapped opportunity that the pharmaceutical, clinical and regulatory communities should consider.

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Abbreviations

COPD:

Chronic Obstructive Pulmonary Disease

DPI:

Dry powder inhalers

NTM:

Non-tuberculous mycobacteria

MDR:

Multidrug drug resistant

POA:

Pyrazinoic acid

PAEs:

Pyrazinoic acid esters

PDP:

Pyrazinoic acid/ester dry powder

XDR:

Extensively drug resistant

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ACKNOWLEDGMENTS AND DISCLOSURES

We acknowledge extensive discussions with Mr. Howard Keith Miller and thank Dr. Barry R. Bloom for feedback on the manuscript. SE is CEO and owner of Collaborations Pharmaceuticals, Inc., and has filed a provisional patent “Treatment for Tuberculosis”. AJH has filed a provisional patent “Dry powder formulations of antituberculosis drug methods of treatment and using the same” and PCT/US2018/36351 “CPZEN compositions and uses”.

Funding

SE, MB and AJH gratefully acknowledge funding from the Department of Defense grant # W81XWH1810802. MB and AJH acknowledge funding from NIAID R21AI131241, the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Award 1UL1TR001111, NC TraCS 4DR31502 and the AIDS Clinical Trials Group (ACTG) UM1 through Grant Award AI068636 award.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Miriam Braunstein

  2. RTI International, Research Triangle Park, North Carolina, USA

    Anthony J. Hickey

  3. UNC Catalyst for Rare Diseases, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Anthony J. Hickey & Sean Ekins

  4. Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina, USA

    Sean Ekins

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  1. Miriam Braunstein
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All authors wrote the manuscript and reviewed the final version.

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Correspondence to Sean Ekins.

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Braunstein, M., Hickey, A.J. & Ekins, S. Why Wait? The Case for Treating Tuberculosis with Inhaled Drugs. Pharm Res 36, 166 (2019). https://doi.org/10.1007/s11095-019-2704-6

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