@article{e42c7214326b40d381eb3f4b3b8d2d4b,
title = "Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive",
abstract = "Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug{\textquoteright}s efficacy. Four macaques were infused with a low dose (75–80 mg/kg) followed by a recovery period and a subsequent high dose (125–130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.",
author = "O{\textquoteright}Rand, {Michael G.} and Hamil, {Katherine G.} and Tiffany Adevai and Mary Zelinski",
note = "Funding Information: This work was supported by NIH grant R41HD084077 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to Michael G. O{\textquoteright}Rand and in part by the North Carolina Biotechnology Center. Research reported in this publication was supported by the Office of the Director, National Institutes of Health of the National Institutes of Health under Award Number P51OD011092. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Eppin Pharma Inc. provided general laboratory supplies and lab space, and financial support in for the form of a salary for Katherine G. Hamil. The specific role of this author is articulated in the{\textquoteright}author contributions{\textquoteright} section. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are grateful for Dr. Lisa Houser, Behavioral Sciences Unit, ONPRC, for training the males for semen collection. We also thank the following members of the Department of Comparative Medicine, ONPRC: Bryn Nelson, Breanna Kolwitz, Marie Clarkson and Heather Panaro for their expertise and assistance in semen collections; Dr. Lauren Drew Martin, DVM, Tiah Schwartz and Brian Schmaling, Surgical Services Unit, for conducting the infusions; and Dr. Heather Sidener, DVM, for careful monitoring of animal health. The authors thank Dr. G. Kopf and Dr. J. Amory for critical reading of the manuscript. Publisher Copyright: {\textcopyright} 2018 O{\textquoteright}Rand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2018",
month = apr,
doi = "10.1371/journal.pone.0195953",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",
}