Efficacy of a GnRH agonist delivered via a slow release implant technology to control reproductive function of the female bovine reproductive axis

Summary

Silicone implants containing deslorelin were shown to reduce serum testosterone and boar taint in male pigs.  The MDC was approached to share the cost of developing this technology for use in female cattle.

Proof of concept study. 

Cattle of mixed breed (Bos taurus and Bos indicus) were treated sub-cutaneously in the ear with silicone implants containing deslorelin. Five formulation variations of the implants, containing either 10 or 12 mg deslorelin were assessed for suppression of oestrous in cattle. Efficacy was assessed on a monthly basis by ovarian ultra sonography with a target suppression rate of >95%. The most effective formulations provided up to 7 months suppression of oestrous in both Bos taurus and Bos indicus cattle.
Formulation refinement.

A series of in vitro payout studies were conducted to optimise the formulation.

In vivo studies

Part 1 - Cattle of mixed breed (Bos taurus and Bos indicus) were treated sub-cutaneously in the ear with silicone implants containing deslorelin. Six formulation variations of the implants, containing a range of deslorelin doses from 4 to 14 mg. were assessed for suppression of oestrous in cattle. The implants were unsuccessful.  This failure was attributed to manufacturing issues.

Part 2 - Cattle of mixed breed (Bos taurus and Bos indicus) were treated sub-cutaneously in the ear with improved silicone implants containing deslorelin or triptorelin. Four formulation variations of the implants, containing either 14 mg deslorelin or triptorelin, were assessed for suppression of oestrous in cattle. Efficacy was assessed on a monthly basis by ovarian ultra sonography with a target suppression rate of >95%. All groups showed oestrus suppression until day 90. Cattle in Groups 2 and 5 showed suppressed ovarian function for approximately 90 and 118 days, respectively, after which animals progressively returned to normal ovarian function including ovulation. The majority of cattle in Group 4 showed suppressed follicular growth up to day 189. Group 3 showed suppressed follicular growth in 100% of animals up to and including Day 189.  This formulation was selected for further development and optimisation.  However the pharmaceutical company and the Australian owner of the intellectual property were unable to agree on the next steps in the formulation development process and how to scale up for commercialisation.  The pharmaceutical company was then involved in takeover of another company and in light of the manufacturing and commercialisation difficulties decided to focus research efforts into other areas.  The pharmaceutical company therefore moved to terminate the project by mutual agreement and the MDC was unable to progress the product further.