Antileishmanial Drug Discovery and Development: Time to Reset the Model?
Leishmaniasis is a vector-borne parasitic disease caused by <i>Leishmania</i> species. The disease affects humans and animals, particularly dogs, provoking cutaneous, mucocutaneous, or visceral processes depending on the <i>Leishmania</i> sp. and the host immune response. No...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/12/2500 |
| _version_ | 1827670999117594624 |
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| author | Ana Isabel Olías-Molero Concepción de la Fuente Montserrat Cuquerella Juan J. Torrado José M. Alunda |
| author_facet | Ana Isabel Olías-Molero Concepción de la Fuente Montserrat Cuquerella Juan J. Torrado José M. Alunda |
| author_sort | Ana Isabel Olías-Molero |
| collection | DOAJ |
| description | Leishmaniasis is a vector-borne parasitic disease caused by <i>Leishmania</i> species. The disease affects humans and animals, particularly dogs, provoking cutaneous, mucocutaneous, or visceral processes depending on the <i>Leishmania</i> sp. and the host immune response. No vaccine for humans is available, and the control relies mainly on chemotherapy. However, currently used drugs are old, some are toxic, and the safer presentations are largely unaffordable by the most severely affected human populations. Moreover, its efficacy has shortcomings, and it has been challenged by the growing reports of resistance and therapeutic failure. This manuscript presents an overview of the currently used drugs, the prevailing model to develop new antileishmanial drugs and its low efficiency, and the impact of deconstruction of the drug pipeline on the high failure rate of potential drugs. To improve the predictive value of preclinical research in the chemotherapy of leishmaniasis, several proposals are presented to circumvent critical hurdles—namely, lack of common goals of collaborative research, particularly in public–private partnership; fragmented efforts; use of inadequate surrogate models, especially for in vivo trials; shortcomings of target product profile (TPP) guides. |
| first_indexed | 2024-03-10T03:31:59Z |
| format | Article |
| id | doaj.art-147b76a9b8324a3096e505caac663796 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T03:31:59Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-147b76a9b8324a3096e505caac6637962023-11-23T09:38:54ZengMDPI AGMicroorganisms2076-26072021-12-01912250010.3390/microorganisms9122500Antileishmanial Drug Discovery and Development: Time to Reset the Model?Ana Isabel Olías-Molero0Concepción de la Fuente1Montserrat Cuquerella2Juan J. Torrado3José M. Alunda4Department of Animal Health, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Animal Health, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Animal Health, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Pharmaceutics and Food Technology, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartment of Animal Health, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainLeishmaniasis is a vector-borne parasitic disease caused by <i>Leishmania</i> species. The disease affects humans and animals, particularly dogs, provoking cutaneous, mucocutaneous, or visceral processes depending on the <i>Leishmania</i> sp. and the host immune response. No vaccine for humans is available, and the control relies mainly on chemotherapy. However, currently used drugs are old, some are toxic, and the safer presentations are largely unaffordable by the most severely affected human populations. Moreover, its efficacy has shortcomings, and it has been challenged by the growing reports of resistance and therapeutic failure. This manuscript presents an overview of the currently used drugs, the prevailing model to develop new antileishmanial drugs and its low efficiency, and the impact of deconstruction of the drug pipeline on the high failure rate of potential drugs. To improve the predictive value of preclinical research in the chemotherapy of leishmaniasis, several proposals are presented to circumvent critical hurdles—namely, lack of common goals of collaborative research, particularly in public–private partnership; fragmented efforts; use of inadequate surrogate models, especially for in vivo trials; shortcomings of target product profile (TPP) guides.https://www.mdpi.com/2076-2607/9/12/2500leishmaniasisvisceral leishmaniasis<i>Leishmania</i>chemotherapydrug discoverydrug pipeline |
| spellingShingle | Ana Isabel Olías-Molero Concepción de la Fuente Montserrat Cuquerella Juan J. Torrado José M. Alunda Antileishmanial Drug Discovery and Development: Time to Reset the Model? Microorganisms leishmaniasis visceral leishmaniasis <i>Leishmania</i> chemotherapy drug discovery drug pipeline |
| title | Antileishmanial Drug Discovery and Development: Time to Reset the Model? |
| title_full | Antileishmanial Drug Discovery and Development: Time to Reset the Model? |
| title_fullStr | Antileishmanial Drug Discovery and Development: Time to Reset the Model? |
| title_full_unstemmed | Antileishmanial Drug Discovery and Development: Time to Reset the Model? |
| title_short | Antileishmanial Drug Discovery and Development: Time to Reset the Model? |
| title_sort | antileishmanial drug discovery and development time to reset the model |
| topic | leishmaniasis visceral leishmaniasis <i>Leishmania</i> chemotherapy drug discovery drug pipeline |
| url | https://www.mdpi.com/2076-2607/9/12/2500 |
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