Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis

Scott G. Franzblau, Mary Ann Degroote, Sang Hyun Cho, Koen Andries, Eric Nuermberger, Ian M. Orme, Khisimuzi Mdluli, Iñigo Angulo-Barturen, Thomas Dick, Veronique Dartois, Anne J. Lenaerts

Research output: Contribution to journalArticle

Abstract

In drug development, there are typically a series of preclinical studies that must be completed with new compounds or regimens before use in humans. A sequence of in vitro assays followed by in vivo testing in validated animal models to assess the activity against Mycobacterium tuberculosis, pharmacology and toxicity is generally used for advancing compounds against tuberculosis in a preclinical stage. A plethora of different assay systems and conditions are used to study the effect of drug candidates on the growth of M. tuberculosis, making it difficult to compare data from one laboratory to another. The Bill and Melinda Gates Foundation recognized the scientific gap to delineate the spectrum of variables in experimental protocols, identify which of these are biologically significant, and converge towards a rationally derived standard set of optimized assays for evaluating compounds. The goals of this document are to recommend protocols and hence accelerate the process of TB drug discovery and testing. Data gathered from preclinical in vitro and in vivo assays during personal visits to laboratories and an electronic survey of methodologies sent to investigators is reported. Comments, opinions, experiences as well as final recommendations from those currently engaged in such preclinical studies for TB drug testing are being presented. Certain in vitro assays and mouse efficacy models were re-evaluated in the laboratory as head-to-head experiments and a summary is provided on the results obtained. It is our hope that this information will be a valuable resource for investigators in the field to move forward in an efficient way and that key variables of assays are included to ensure accuracy of results which can then be used for designing human clinical trials. This document then concludes with remaining questions and critical gaps that are in need of further validation and experimentation.

Original languageEnglish (US)
Pages (from-to)453-488
Number of pages36
JournalTuberculosis
Volume92
Issue number6
DOIs
StatePublished - Nov 2012

Fingerprint

Mycobacterium tuberculosis
Research Personnel
Pharmaceutical Preparations
Drug Discovery
Tuberculosis
Animal Models
Clinical Trials
Pharmacology
Growth
In Vitro Techniques

Keywords

  • Animal models
  • Drugs
  • Efficacy testing
  • Historic review
  • In vitro
  • In vivo
  • Relapse
  • Screening methods
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Franzblau, S. G., Degroote, M. A., Cho, S. H., Andries, K., Nuermberger, E., Orme, I. M., ... Lenaerts, A. J. (2012). Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis. Tuberculosis, 92(6), 453-488. https://doi.org/10.1016/j.tube.2012.07.003

Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis. / Franzblau, Scott G.; Degroote, Mary Ann; Cho, Sang Hyun; Andries, Koen; Nuermberger, Eric; Orme, Ian M.; Mdluli, Khisimuzi; Angulo-Barturen, Iñigo; Dick, Thomas; Dartois, Veronique; Lenaerts, Anne J.

In: Tuberculosis, Vol. 92, No. 6, 11.2012, p. 453-488.

Research output: Contribution to journalArticle

Franzblau, SG, Degroote, MA, Cho, SH, Andries, K, Nuermberger, E, Orme, IM, Mdluli, K, Angulo-Barturen, I, Dick, T, Dartois, V & Lenaerts, AJ 2012, 'Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis', Tuberculosis, vol. 92, no. 6, pp. 453-488. https://doi.org/10.1016/j.tube.2012.07.003
Franzblau, Scott G. ; Degroote, Mary Ann ; Cho, Sang Hyun ; Andries, Koen ; Nuermberger, Eric ; Orme, Ian M. ; Mdluli, Khisimuzi ; Angulo-Barturen, Iñigo ; Dick, Thomas ; Dartois, Veronique ; Lenaerts, Anne J. / Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis. In: Tuberculosis. 2012 ; Vol. 92, No. 6. pp. 453-488.
@article{3d8d7dbd80a44148af5b26d3d7e8c3d0,
title = "Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis",
abstract = "In drug development, there are typically a series of preclinical studies that must be completed with new compounds or regimens before use in humans. A sequence of in vitro assays followed by in vivo testing in validated animal models to assess the activity against Mycobacterium tuberculosis, pharmacology and toxicity is generally used for advancing compounds against tuberculosis in a preclinical stage. A plethora of different assay systems and conditions are used to study the effect of drug candidates on the growth of M. tuberculosis, making it difficult to compare data from one laboratory to another. The Bill and Melinda Gates Foundation recognized the scientific gap to delineate the spectrum of variables in experimental protocols, identify which of these are biologically significant, and converge towards a rationally derived standard set of optimized assays for evaluating compounds. The goals of this document are to recommend protocols and hence accelerate the process of TB drug discovery and testing. Data gathered from preclinical in vitro and in vivo assays during personal visits to laboratories and an electronic survey of methodologies sent to investigators is reported. Comments, opinions, experiences as well as final recommendations from those currently engaged in such preclinical studies for TB drug testing are being presented. Certain in vitro assays and mouse efficacy models were re-evaluated in the laboratory as head-to-head experiments and a summary is provided on the results obtained. It is our hope that this information will be a valuable resource for investigators in the field to move forward in an efficient way and that key variables of assays are included to ensure accuracy of results which can then be used for designing human clinical trials. This document then concludes with remaining questions and critical gaps that are in need of further validation and experimentation.",
keywords = "Animal models, Drugs, Efficacy testing, Historic review, In vitro, In vivo, Relapse, Screening methods, Tuberculosis",
author = "Franzblau, {Scott G.} and Degroote, {Mary Ann} and Cho, {Sang Hyun} and Koen Andries and Eric Nuermberger and Orme, {Ian M.} and Khisimuzi Mdluli and I{\~n}igo Angulo-Barturen and Thomas Dick and Veronique Dartois and Lenaerts, {Anne J.}",
year = "2012",
month = "11",
doi = "10.1016/j.tube.2012.07.003",
language = "English (US)",
volume = "92",
pages = "453--488",
journal = "Tuberculosis",
issn = "1472-9792",
publisher = "Churchill Livingstone",
number = "6",

}

TY - JOUR

T1 - Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis

AU - Franzblau, Scott G.

AU - Degroote, Mary Ann

AU - Cho, Sang Hyun

AU - Andries, Koen

AU - Nuermberger, Eric

AU - Orme, Ian M.

AU - Mdluli, Khisimuzi

AU - Angulo-Barturen, Iñigo

AU - Dick, Thomas

AU - Dartois, Veronique

AU - Lenaerts, Anne J.

PY - 2012/11

Y1 - 2012/11

N2 - In drug development, there are typically a series of preclinical studies that must be completed with new compounds or regimens before use in humans. A sequence of in vitro assays followed by in vivo testing in validated animal models to assess the activity against Mycobacterium tuberculosis, pharmacology and toxicity is generally used for advancing compounds against tuberculosis in a preclinical stage. A plethora of different assay systems and conditions are used to study the effect of drug candidates on the growth of M. tuberculosis, making it difficult to compare data from one laboratory to another. The Bill and Melinda Gates Foundation recognized the scientific gap to delineate the spectrum of variables in experimental protocols, identify which of these are biologically significant, and converge towards a rationally derived standard set of optimized assays for evaluating compounds. The goals of this document are to recommend protocols and hence accelerate the process of TB drug discovery and testing. Data gathered from preclinical in vitro and in vivo assays during personal visits to laboratories and an electronic survey of methodologies sent to investigators is reported. Comments, opinions, experiences as well as final recommendations from those currently engaged in such preclinical studies for TB drug testing are being presented. Certain in vitro assays and mouse efficacy models were re-evaluated in the laboratory as head-to-head experiments and a summary is provided on the results obtained. It is our hope that this information will be a valuable resource for investigators in the field to move forward in an efficient way and that key variables of assays are included to ensure accuracy of results which can then be used for designing human clinical trials. This document then concludes with remaining questions and critical gaps that are in need of further validation and experimentation.

AB - In drug development, there are typically a series of preclinical studies that must be completed with new compounds or regimens before use in humans. A sequence of in vitro assays followed by in vivo testing in validated animal models to assess the activity against Mycobacterium tuberculosis, pharmacology and toxicity is generally used for advancing compounds against tuberculosis in a preclinical stage. A plethora of different assay systems and conditions are used to study the effect of drug candidates on the growth of M. tuberculosis, making it difficult to compare data from one laboratory to another. The Bill and Melinda Gates Foundation recognized the scientific gap to delineate the spectrum of variables in experimental protocols, identify which of these are biologically significant, and converge towards a rationally derived standard set of optimized assays for evaluating compounds. The goals of this document are to recommend protocols and hence accelerate the process of TB drug discovery and testing. Data gathered from preclinical in vitro and in vivo assays during personal visits to laboratories and an electronic survey of methodologies sent to investigators is reported. Comments, opinions, experiences as well as final recommendations from those currently engaged in such preclinical studies for TB drug testing are being presented. Certain in vitro assays and mouse efficacy models were re-evaluated in the laboratory as head-to-head experiments and a summary is provided on the results obtained. It is our hope that this information will be a valuable resource for investigators in the field to move forward in an efficient way and that key variables of assays are included to ensure accuracy of results which can then be used for designing human clinical trials. This document then concludes with remaining questions and critical gaps that are in need of further validation and experimentation.

KW - Animal models

KW - Drugs

KW - Efficacy testing

KW - Historic review

KW - In vitro

KW - In vivo

KW - Relapse

KW - Screening methods

KW - Tuberculosis

UR - http://www.scopus.com/inward/record.url?scp=84867334162&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867334162&partnerID=8YFLogxK

U2 - 10.1016/j.tube.2012.07.003

DO - 10.1016/j.tube.2012.07.003

M3 - Article

C2 - 22940006

AN - SCOPUS:84867334162

VL - 92

SP - 453

EP - 488

JO - Tuberculosis

JF - Tuberculosis

SN - 1472-9792

IS - 6

ER -