Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they neg...

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Detalles Bibliográficos
Autores principales: Sterkel, Marcos, Haines, Lee R., Casas Sanchez, Aitor, Adung'a, Vincent O., Vionette Amaral, Raquel J., Quek, Shannon, Rose, Clair, Santos, Mariana Silva dos, Escude, Natalia Garcia, Ismael, Hanafy, Paine, Mark I., Barribeau, Seth M., Wagstaff, Simon C., MacRae, James I., Masiga, Daniel K., Yakob, Laith, Oliveira, Pedro L., Acosta Serrano, Alvaro
Formato: Articulo
Lenguaje:Inglés
Publicado: 2021
Materias:
Biología
Gene silencing
Virology
Rna interference
Tyrosine
Transmission (medicine)
African trypanosomiasis
Nitisinone
Drug
Orphan drug
Biology
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/125073
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-125073
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Gene silencing
Virology
Rna interference
Tyrosine
Transmission (medicine)
African trypanosomiasis
Nitisinone
Drug
Orphan drug
Biology
spellingShingle Biología
Gene silencing
Virology
Rna interference
Tyrosine
Transmission (medicine)
African trypanosomiasis
Nitisinone
Drug
Orphan drug
Biology
Sterkel, Marcos
Haines, Lee R.
Casas Sanchez, Aitor
Adung'a, Vincent O.
Vionette Amaral, Raquel J.
Quek, Shannon
Rose, Clair
Santos, Mariana Silva dos
Escude, Natalia Garcia
Ismael, Hanafy
Paine, Mark I.
Barribeau, Seth M.
Wagstaff, Simon C.
MacRae, James I.
Masiga, Daniel K.
Yakob, Laith
Oliveira, Pedro L.
Acosta Serrano, Alvaro
Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis
topic_facet Biología
Gene silencing
Virology
Rna interference
Tyrosine
Transmission (medicine)
African trypanosomiasis
Nitisinone
Drug
Orphan drug
Biology
description Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce insect pollinator species. Here we present a promising, environment-friendly alternative that targets insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded. RNAi silencing of either the first two enzymes in the tyrosine degradation pathway (TAT and HPPD) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, it did not affect bumblebee survival. A mathematical model shows that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current elimination programmes.
format Articulo
Articulo
author Sterkel, Marcos
Haines, Lee R.
Casas Sanchez, Aitor
Adung'a, Vincent O.
Vionette Amaral, Raquel J.
Quek, Shannon
Rose, Clair
Santos, Mariana Silva dos
Escude, Natalia Garcia
Ismael, Hanafy
Paine, Mark I.
Barribeau, Seth M.
Wagstaff, Simon C.
MacRae, James I.
Masiga, Daniel K.
Yakob, Laith
Oliveira, Pedro L.
Acosta Serrano, Alvaro
author_facet Sterkel, Marcos
Haines, Lee R.
Casas Sanchez, Aitor
Adung'a, Vincent O.
Vionette Amaral, Raquel J.
Quek, Shannon
Rose, Clair
Santos, Mariana Silva dos
Escude, Natalia Garcia
Ismael, Hanafy
Paine, Mark I.
Barribeau, Seth M.
Wagstaff, Simon C.
MacRae, James I.
Masiga, Daniel K.
Yakob, Laith
Oliveira, Pedro L.
Acosta Serrano, Alvaro
author_sort Sterkel, Marcos
title Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis
title_short Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis
title_full Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis
title_fullStr Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis
title_full_unstemmed Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis
title_sort repurposing the orphan drug nitisinone to control the transmission of african trypanosomiasis
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/125073
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