Preclinical development of an oral anti-Wolbachia macrolide drug for the treatment of lymphatic filariasis and onchocerciasis

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Science Translational Medicine  13 Mar 2019:
Vol. 11, Issue 483, eaau2086
DOI: 10.1126/scitranslmed.aau2086

Nematodes go A·WOL

New drugs are urgently needed for treating the neglected tropical diseases, onchocerciasis and lymphatic filariasis. As part of the A·WOL consortium, Taylor et al. launched a drug discovery program that identified macrolide antibiotic molecules that were capable of eliminating the bacterial endosymbiont, Wolbachia, which is necessary for the viability and fertility of filarial worms. Two macrolide compounds cleared Wolbachia from filarial nematodes in animal models of lymphatic filariasis and onchocerciasis. The authors showed that the tylosin A analog, A-1574083 (ABBV-4083), had superior efficacy compared to tetracycline antibiotics for clearing Wolbachia in mouse and gerbil models of filarial infection. The safety and pharmacology profiles of A-1574083 have enabled this compound to be moved forward into clinical testing.

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