Academic Journal
Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections.
| Title: | Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections. |
|---|---|
| Authors: | Andrea Schiefer, Marc P Hübner, Anna Krome, Christine Lämmer, Alexandra Ehrens, Tilman Aden, Marianne Koschel, Helene Neufeld, Lillibeth Chaverra-Muñoz, Rolf Jansen, Stefan Kehraus, Gabriele M König, Domen Pogorevc, Rolf Müller, Marc Stadler, Stephan Hüttel, Thomas Hesterkamp, Karl Wagner, Kenneth Pfarr, Achim Hoerauf |
| Source: | PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0008930 (2020) |
| Publisher Information: | Public Library of Science (PLoS), 2020. |
| Publication Year: | 2020 |
| Collection: | LCC:Arctic medicine. Tropical medicine LCC:Public aspects of medicine |
| Subject Terms: | Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270 |
| More Details: | Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal-adult-worm killing-treatment. Anti-wolbachial antibiotics, e.g. doxycycline, target the essential Wolbachia endosymbionts of filariae and are a safe prototype adult-worm-sterilizing and macrofilaricidal regimen, in contrast to standard treatments with ivermectin or diethylcarbamazine, which mainly target the microfilariae. However, treatment regimens of 4-5 weeks necessary for doxycycline and contraindications limit its use. Therefore, we tested the preclinical anti-Wolbachia drug candidate Corallopyronin A (CorA) for in vivo efficacy during initial and chronic filarial infections in the Litomosoides sigmodontis rodent model. CorA treatment for 14 days beginning immediately after infection cleared >90% of Wolbachia endosymbionts from filariae and prevented development into adult worms. CorA treatment of patently infected microfilaremic gerbils for 14 days with 30 mg/kg twice a day (BID) achieved a sustained reduction of >99% of Wolbachia endosymbionts from adult filariae and microfilariae, followed by complete inhibition of filarial embryogenesis resulting in clearance of microfilariae. Combined treatment of CorA and albendazole, a drug currently co-administered during mass drug administrations and previously shown to enhance efficacy of anti-Wolbachia drugs, achieved microfilarial clearance after 7 days of treatment at a lower BID dose of 10 mg/kg CorA, a Human Equivalent Dose of 1.4 mg/kg. Importantly, this combination led to a significant reduction in the adult worm burden, which has not yet been published with other anti-Wolbachia candidates tested in this model. In summary, CorA is a preclinical candidate for filariasis, which significantly reduces treatment times required to achieve sustained Wolbachia depletion, clearance of microfilariae, and inhibition of embryogenesis. In combination with albendazole, CorA is robustly macrofilaricidal after 7 days of treatment and fulfills the Target Product Profile for a macrofilaricidal drug. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1935-2727 1935-2735 |
| Relation: | https://doaj.org/toc/1935-2727; https://doaj.org/toc/1935-2735 |
| DOI: | 10.1371/journal.pntd.0008930 |
| Access URL: | https://doaj.org/article/d4370a71cad149209e66761eb918df85 |
| Accession Number: | edsdoj.4370a71cad149209e66761eb918df85 |
| Database: | Directory of Open Access Journals |
| Full text is not displayed to guests. | Login for full access. |
| ISSN: | 19352727 19352735 |
|---|---|
| DOI: | 10.1371/journal.pntd.0008930 |
| Published in: | PLoS Neglected Tropical Diseases |
| Language: | English |