Onchocerciasis Drug Discovery

Filarial nematode phenotypic screening cascade to identify compounds with anti-parasitic activity for drug discovery optimization

“…The need for repeated drug administration, concerns about serious L. loa -related adverse events, and the possible emergence of ivermectin-resistant O. volvulus have heightened the need for compounds that exhibit adult stage selectivity (macrofilaricidal) or long-lasting sterilizing effects ( Hawryluk, 2020 ). Current efforts to control and eliminate onchocerciasis are hindered by the lack of medicines that target the adult worm stage ( Hawryluk and Scandale, 2019 ). In addition, a major challenge hampering drug discovery is finding suitable preclinical animal models, as O. volvulus can only develop fully in humans and primates.…”

Discovery of Substituted Di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines as Novel Macrofilaricidal Compounds for the Treatment of Human Filarial Infections

“…These treatments only temporarily stop transmission, thereby requiring repeat treatments for up to 15 years, depending on the disease. 2 The need for repeated drug administration, concerns about serious Loa loa-related adverse events, 3 and the possible emergence of ivermectin-resistant O. volvulus have heightened the need for compounds that exhibit adult stage selectivity (macrofilaricidal) or long-lasting sterilizing effects. 4 Current efforts to control and eliminate onchocerciasis are hindered by the lack of medicines that target the adult worm stage.…”

“…4 Current efforts to control and eliminate onchocerciasis are hindered by the lack of medicines that target the adult worm stage. 2 In addition, a major challenge hampering drug discovery is finding suitable preclinical animal models as O. volvulus can only develop fully in humans and primates. While assays for testing against O. volvulus have been established, they have limitations.…”

“…Current therapies target the juvenile worms (microfilariae), allowing adult worms to continue producing microfilariae. These treatments only temporarily stop transmission, thereby requiring repeat treatments for up to 15 years, depending on the disease . The need for repeated drug administration, concerns about serious Loa loa -related adverse events, and the possible emergence of ivermectin-resistant O.…”

“…Current efforts to control and eliminate onchocerciasis are hindered by the lack of medicines that target the adult worm stage . In addition, a major challenge hampering drug discovery is finding suitable preclinical animal models as O.…”