2. Academic Validation
  3. Discovery of ABBV-4083, a novel analog of Tylosin A that has potent anti-Wolbachia and anti-filarial activity

Discovery of ABBV-4083, a novel analog of Tylosin A that has potent anti-Wolbachia and anti-filarial activity

  • PLoS Negl Trop Dis. 2019 Feb 28;13(2):e0007159. doi: 10.1371/journal.pntd.0007159.
Thomas W von Geldern 1 2,  Howard E Morton 1,  Rick F Clark 1,  Brian S Brown 1,  Kelly L Johnston 3,  Louise Ford 3,  Sabine Specht 4,  Robert A Carr 1,  Deanne F Stolarik 1,  Junli Ma 1,  Matthew J Rieser 1,  Dominique Struever 4,  Stefan J Frohberger 4,  Marianne Koschel 4,  Alexandra Ehrens 4,  Joseph D Turner 3,  Marc P Hübner 4,  Achim Hoerauf 4,  Mark J Taylor 3,  Stephen A Ward 3,  Kennan Marsh 1,  Dale J Kempf 1
Affiliations

Affiliations

  • 1 Global Pharmaceutical Research and Development, AbbVie, North Chicago, Illinois, United States of America.
  • 2 Franciscan Institute for World Health, Franciscan University, Steubenville, Ohio, United States of America.
  • 3 Centre for Drugs and Diagnostics, Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
  • 4 Institute for Medical Microbiology, Immunology and Parasitology, University Hospital, Bonn, Germany.
PMID: 30818326 DOI: 10.1371/journal.pntd.0007159
Abstract

There is a significant need for improved treatments for onchocerciasis and lymphatic filariasis, diseases caused by filarial worm Infection. In particular, an agent able to selectively kill adult worms (macrofilaricide) would be expected to substantially augment the benefits of mass drug administration (MDA) with current microfilaricides, and to provide a solution to treatment of onchocerciasis / loiasis co-infection, where MDA is restricted. We have identified a novel macrofilaricidal agent, Tylosin A (TylA), which acts by targeting the worm-symbiont Wolbachia bacterium. Chemical modification of TylA leads to improvements in anti-Wolbachia activity and oral pharmacokinetic properties; an optimized analog (ABBV-4083) has been selected for clinical evaluation.

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