Intestinal UDP-glucuronosyltransferase as a potential target for the treatment and prevention of lymphatic filariasis.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "Intestinal UDP-glucuronosyltransferase as a potential target for the treatment and prevention of lymphatic filariasis."

Lymphatic filariasis (LF), a morbid disease caused by the tissue-invasive nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori, affects millions of people worldwide. Global eradication efforts have significantly reduced worldwide prevalence, but complete elimination has been hampered by limitations of current anti-filarial drugs and the lack of a vaccine. The goal of this study was to evaluate B. malayi intestinal UDP-glucuronosyltransferase (Bm-UGT) as a potential therapeutic target. To evaluate whether Bm-UGT is essential for adult filarial worms, we inhibited its expression using siRNA. This resulted in a 75% knockdown of Bm-ugt mRNA for 6 days and almost complete suppression of detectable Bm-UGT by immunoblot. Reduction in Bm-UGT expression resulted in decreased worm motility for 6 days, 70% reduction in microfilaria release from adult worms, and significant reduction in adult worm metabolism as detected by MTT assays. Because prior allergic-sensitization to a filarial antigen would be a contraindication for its use as a vaccine candidate, we tested plasma from infected and endemic normal populations for Bm-UGT-specific IgE using a luciferase immunoprecipitation assay. All samples (n = 35) tested negative. We then tested two commercially available medicines known to be broad inhibitors of UGTs, sulfinpyrazone and probenecid, for in vitro activity against B. malayi. There were marked macrofilaricidal effects at concentrations achievable in humans and very little effect on microfilariae. In addition, we observed that probenecid and sulfinpyrazone exhibit a synergistic macrofilaricidal effect when used in combination with albendazole. The results of this study demonstrate that Bm-UGT is an essential protein for adult worm survival. Lack of prior IgE sensitization in infected and endemic populations suggest it may be a feasible vaccine candidate. The finding that sulfinpyrazone and probenecid have in vitro effects against adult B. malayi worms suggests that these medications have promise as potential macrofilaricides in humans.


Journal Details

This article was published in the following journal.

Name: PLoS neglected tropical diseases
ISSN: 1935-2735
Pages: e0007687


DeepDyve research library

PubMed Articles [35002 Associated PubMed Articles listed on BioPortfolio]

Culex species diversity, susceptibility to insecticides and role as potential vector of Lymphatic filariasis in the city of Yaoundé, Cameroon.

Culex species are widespread across Cameroon and responsible for high burden of nuisance in most urban settings. However, despite their high nuisance, they remain less studied compared to anophelines....

Boron-Pleuromutilins as Anti-Wolbachia Agents with Potential for Treatment of Onchocerciasis and Lymphatic Filariasis.

A series of pleuromutilins modified by introduction of a boron-containing heterocycle on C(14) of the polycyclic core are described. These analogs were found to be potent anti-Wolbachia antibiotics, a...

The safety of double- and triple-drug community mass drug administration for lymphatic filariasis: A multicenter, open-label, cluster-randomized study.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Rece...

Mapping of lymphatic filariasis in loiasis areas: A new strategy shows no evidence for Wuchereria bancrofti endemicity in Cameroon.

Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cr...

Systematic sampling of adults as a sensitive means of detecting persistence of lymphatic filariasis following mass drug administration in Sri Lanka.

Sri Lanka's Anti-Filariasis Campaign conducted 5 annual rounds of mass drug administration (MDA) with diethylcarbamazine (DEC) plus albendazole to eliminate lymphatic filariasis (LF) in all endemic di...

Clinical Trials [10023 Associated Clinical Trials listed on BioPortfolio]

Death to Onchocerciasis and Lymphatic Filariasis (DOLF) Triple Drug Therapy for Lymphatic Filariasis

The DOLF Triple Drug Therapy for Lymphatic Filariasis study will determine the frequency, type and severity of adverse events following triple-drug therapy (IVM+DEC+ALB, IDA) compared to t...

Prevalence Studies After Triple Drug Therapy for Lymphatic Filariasis

This study will assess the impact of 2-drug (DA) or 3-drug (IDA) regimens on lymphatic filariasis infection parameters in communities. Parameters measured will include: circulating filaria...

Research for Elimination of Lymphatic Filariasis (ICIDR)

The purpose of this study is to check blood samples for lymphatic filariasis to determine whether the recent Program to Eliminate Lymphatic Filariasis was successful in controlling lymphat...

Impact of Albendazole -Ivermectin on Wuchereria Bancrofti in Mali

Lymphatic filariasis is a public health problem in Mali. The existing data are not up to date and most of them are more than 15 years old. To address this issue in April 2000, the investig...

Research for Elim of Filariasis

Wuchereria bancrofti, is a mosquito-transmitted parasite that causes deforming lymphatic filariasis in the tropics. Improved treatment methods have led to new thinking that it should be po...

Medical and Biotech [MESH] Definitions

Parasitic infestation of the human lymphatic system by WUCHERERIA BANCROFTI or BRUGIA MALAYI. It is also called lymphatic filariasis.

Dilatation of the intestinal lymphatic system usually caused by an obstruction in the intestinal wall. It may be congenital or acquired and is characterized by DIARRHEA; HYPOPROTEINEMIA; peripheral and/or abdominal EDEMA; and PROTEIN-LOSING ENTEROPATHIES.

A morpholine and thiophene derivative that functions as a FACTOR XA INHIBITOR and is used in the treatment and prevention of DEEP-VEIN THROMBOSIS and PULMONARY EMBOLISM. It is also used for the prevention of STROKE and systemic embolization in patients with non-valvular ATRIAL FIBRILLATION, and for the prevention of atherothrombotic events in patients after an ACUTE CORONARY SYNDROME.

An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa.

Diseases that are underfunded and have low name recognition but are major burdens in less developed countries. The World Health Organization has designated six tropical infectious diseases as being neglected in industrialized countries that are endemic in many developing countries (HELMINTHIASIS; LEPROSY; LYMPHATIC FILARIASIS; ONCHOCERCIASIS; SCHISTOSOMIASIS; and TRACHOMA).

Quick Search

DeepDyve research library

Relevant Topics

Tropical Medicine
Tropical Medicine is the study of diseases more commonly found in tropical regions than elsewhere. Examples of these diseases are malaria, yellow fever, Chagas disease, Dengue, Helminths, African trypanosomiasis, Leishmaniasis, Leprosy, Lymphatic filaria...

A vaccine is any preparation intended to produce immunity to a disease by stimulating the production of antibodies. It creates immunity but does not cause the disease. There are several differnt types of vaccine avalable; Killed microorganisms; which s...

Searches Linking to this Article