Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need

Mark C. Field; David Horn; Alan H. Fairlamb; Michael A. J. Ferguson; David W. Gray; Kevin D. Read; Manu De Rycker; Leah S. Torrie; Paul G. Wyatt; Susan Wyllie; Ian H. Gilbert

doi:10.1038/nrmicro.2016.193

Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need

Mark C. Field
, David Horn
, Alan H. Fairlamb
, Michael A. J. Ferguson
, David W. Gray
, Kevin D. Read
, Manu De Rycker
, Leah S. Torrie
, Paul G. Wyatt
, Susan Wyllie
, Ian H. Gilbert (Lead / Corresponding author)

Research output: Contribution to journal › Review article › peer-review

351 Citations (Scopus)

729 Downloads (Pure)

Abstract

The WHO recognizes human African trypanosomiasis, Chagas disease and the leishmaniases as neglected tropical diseases. These diseases are caused by parasitic trypanosomatids and range in severity from mild and self-curing to near invariably fatal. Public health advances have substantially decreased the effect of these diseases in recent decades but alone will not eliminate them. In this Review, we discuss why new drugs against trypanosomatids are required, approaches that are under investigation to develop new drugs and why the drug discovery pipeline remains essentially unfilled. In addition, we consider the important challenges to drug discovery strategies and the new technologies that can address them. The combination of new drugs, new technologies and public health initiatives is essential for the management, and hopefully eventual elimination, of trypanosomatid diseases from the human population.

Original language	English
Pages (from-to)	217-231
Number of pages	15
Journal	Nature Reviews Microbiology
Volume	15
Issue number	4
Early online date	27 Feb 2017
DOIs	https://doi.org/10.1038/nrmicro.2016.193
Publication status	Published - Apr 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Antiparasitic agents
Drug development
Parasite biology
Parasitic infection

Access to Document

10.1038/nrmicro.2016.193

Author Accepted ManuscriptAccepted author manuscript, 367 KB
Author Accepted Manuscript - FiguresAccepted author manuscript, 774 KB

10 Finished

A Systems Approach for Understanding Cell Surface Dynamics in Trypanosomes (Investigator Award)
Field, M. (Investigator)
1/10/17 → 31/03/24
Project: Research
Global Mechanisms for Control of the Trypanosome Proteome: Defining the Composition, Origins and Roles of Cullin E3 Ligases
Field, M. (Investigator)
1/01/17 → 31/12/19
Project: Research
Chemical Biology: Leveraging Phenotypic Hits Against Kinetoplastids (Strategic Grant)
Fairlamb, A. (Investigator), Field, M. (Investigator), Gilbert, I. (Investigator), Gray, D. (Investigator), Horn, D. (Investigator) & Wyatt, P. (Investigator)
1/01/15 → 31/12/20
Project: Research

351 Citations
2 Comment/debate

Erratum to: Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need (Nature Reviews Microbiology, (2017), 15, 4, (217-231), 10.1038/nrmicro.2016.193)
Field, M. C., Horn, D., Fairlamb, A. H., Ferguson, M. A. J., Gray, D. W., Read, K. D., De Rycker, M., Torrie, L. S., Wyatt, P. G., Wyllie, S. & Gilbert, I. H., 1 Nov 2018, In: Nature Reviews Microbiology. 16, 11, 1 p.
Research output: Contribution to journal › Comment/debate › peer-review

Open Access
2 Link opens in a new tab Citations (Scopus)
Erratum: Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need
Field, M. C., Horn, D., Fairlamb, A., Ferguson, M., Gray, D., Read, K., De Rycker, M., Torrie, L., Wyatt, P., Wyllie, S. & Gilbert, I. H., 5 Jun 2017, In: Nature Reviews Microbiology. 15, 1 p., 447.
Research output: Contribution to journal › Comment/debate › peer-review

Open Access
1 Link opens in a new tab Citation (Scopus)

Cite this

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title = "Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need",

abstract = "The WHO recognizes human African trypanosomiasis, Chagas disease and the leishmaniases as neglected tropical diseases. These diseases are caused by parasitic trypanosomatids and range in severity from mild and self-curing to near invariably fatal. Public health advances have substantially decreased the effect of these diseases in recent decades but alone will not eliminate them. In this Review, we discuss why new drugs against trypanosomatids are required, approaches that are under investigation to develop new drugs and why the drug discovery pipeline remains essentially unfilled. In addition, we consider the important challenges to drug discovery strategies and the new technologies that can address them. The combination of new drugs, new technologies and public health initiatives is essential for the management, and hopefully eventual elimination, of trypanosomatid diseases from the human population.",

keywords = "Antiparasitic agents , Drug development , Parasite biology , Parasitic infection",

author = "Field, \{Mark C.\} and David Horn and Fairlamb, \{Alan H.\} and Ferguson, \{Michael A. J.\} and Gray, \{David W.\} and Read, \{Kevin D.\} and \{De Rycker\}, Manu and Torrie, \{Leah S.\} and Wyatt, \{Paul G.\} and Susan Wyllie and Gilbert, \{Ian H.\}",

note = "The authors are grateful to the following funding bodies for financial support: The Wellcome Trust (strategic grants 077705, 083481, 092340, 100476 and 105021), Wellcome Trust Senior Investigator Awards to D.H., M.F. and M.A.J.F. (grants 100320/Z/12/Z, 204697/Z/16/Z and 101842/Z/13/Z) and a Wellcome Trust Principal Research Fellowship to A.H.F (grant 079838); Drugs for Neglected Diseases Initiative (DNDi); and the UK Medical Research Council for grants to M.C.F. (MR/L018853/1 and MR/P009018/1), D.H. (MR/K000500/1) and to M.C.F and D.H. (MR/K008749/1). ",

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issn = "1740-1526",

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T1 - Anti-trypanosomatid drug discovery

T2 - an ongoing challenge and a continuing need

AU - Field, Mark C.

AU - Horn, David

AU - Fairlamb, Alan H.

AU - Ferguson, Michael A. J.

AU - Gray, David W.

AU - Read, Kevin D.

AU - De Rycker, Manu

AU - Torrie, Leah S.

AU - Wyatt, Paul G.

AU - Wyllie, Susan

AU - Gilbert, Ian H.

N1 - The authors are grateful to the following funding bodies for financial support: The Wellcome Trust (strategic grants 077705, 083481, 092340, 100476 and 105021), Wellcome Trust Senior Investigator Awards to D.H., M.F. and M.A.J.F. (grants 100320/Z/12/Z, 204697/Z/16/Z and 101842/Z/13/Z) and a Wellcome Trust Principal Research Fellowship to A.H.F (grant 079838); Drugs for Neglected Diseases Initiative (DNDi); and the UK Medical Research Council for grants to M.C.F. (MR/L018853/1 and MR/P009018/1), D.H. (MR/K000500/1) and to M.C.F and D.H. (MR/K008749/1).

PY - 2017/4

Y1 - 2017/4

N2 - The WHO recognizes human African trypanosomiasis, Chagas disease and the leishmaniases as neglected tropical diseases. These diseases are caused by parasitic trypanosomatids and range in severity from mild and self-curing to near invariably fatal. Public health advances have substantially decreased the effect of these diseases in recent decades but alone will not eliminate them. In this Review, we discuss why new drugs against trypanosomatids are required, approaches that are under investigation to develop new drugs and why the drug discovery pipeline remains essentially unfilled. In addition, we consider the important challenges to drug discovery strategies and the new technologies that can address them. The combination of new drugs, new technologies and public health initiatives is essential for the management, and hopefully eventual elimination, of trypanosomatid diseases from the human population.

AB - The WHO recognizes human African trypanosomiasis, Chagas disease and the leishmaniases as neglected tropical diseases. These diseases are caused by parasitic trypanosomatids and range in severity from mild and self-curing to near invariably fatal. Public health advances have substantially decreased the effect of these diseases in recent decades but alone will not eliminate them. In this Review, we discuss why new drugs against trypanosomatids are required, approaches that are under investigation to develop new drugs and why the drug discovery pipeline remains essentially unfilled. In addition, we consider the important challenges to drug discovery strategies and the new technologies that can address them. The combination of new drugs, new technologies and public health initiatives is essential for the management, and hopefully eventual elimination, of trypanosomatid diseases from the human population.

KW - Antiparasitic agents

KW - Drug development

KW - Parasite biology

KW - Parasitic infection

U2 - 10.1038/nrmicro.2016.193

DO - 10.1038/nrmicro.2016.193

M3 - Review article

C2 - 28239154

SN - 1740-1526

VL - 15

SP - 217

EP - 231

JO - Nature Reviews Microbiology

JF - Nature Reviews Microbiology

IS - 4

ER -

Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need

Abstract

UN SDGs

Keywords

Access to Document

Fingerprint

Projects

A Systems Approach for Understanding Cell Surface Dynamics in Trypanosomes (Investigator Award)

Global Mechanisms for Control of the Trypanosome Proteome: Defining the Composition, Origins and Roles of Cullin E3 Ligases

Chemical Biology: Leveraging Phenotypic Hits Against Kinetoplastids (Strategic Grant)

Research output

Erratum to: Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need (Nature Reviews Microbiology, (2017), 15, 4, (217-231), 10.1038/nrmicro.2016.193)

Erratum: Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need

Cite this