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



Sterkel, Marcos, Haines, Lee, Casas-Sánchez, Aitor, Adung’a, Vincent Owino, Vionette-Amaral, Raquel, Quek, Shannon, Rose, Clair ORCID: 0000-0001-7782-5359, dos Santos, Mariana Silva, Escude, Natalia Garcia, Ismael, Hanafy
et al (show 8 more authors) (2020) Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis.

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Abstract

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.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 15 Sep 2020 07:12
Last Modified: 21 Oct 2021 11:32
DOI: 10.1101/2020.06.08.139808
Open Access URL: https://www.biorxiv.org/content/10.1101/2020.06.08...
URI: https://livrepository.liverpool.ac.uk/id/eprint/3101209