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New Technologies

Dog and Cat Immunocontraception



Duane C. Kraemer, DVM, Ph.D., H-Act, Professor, Department of Veterinary Physiology & Pharmacology, Texas A&M University, College of Veterinary Medicine looks for the answers to cat and dog chemical sterilization.

  

Non-surgical sterilization of dogs and cats is an area of research that has been ongoing for nearly a decade. While there were early successes, nothing heretofore matches the assortment of promising technologies now under development. Dr. Courtney Forbes, D.V.M., Chief of Staff at the SNAP Houston Spay & Neuter Clinic, attended the Third International Symposium on Non-surgical Contraceptive Methods for Pet Population Control on November 9-12, 2006. This symposium, sponsored by the Alliance for Contraception in Cats and Dogs (ACC&D), reviewed the current state of chemical sterilization research.

Background

In mammals, gonadotropin-releasing hormone (GnRH) is a master hormone that is produced in the hypothalamus (a brain structure) and carried to the pituitary (master hormonal coordinator). There it results in the release of FSH and LH. In males, LH and FSH are required for testosterone production by the testes. In females, LH and FSH are required for estrogen production. Reproduction thus halts, in both males and females, when GnRH is removed from the picture. Fortunately an absence of GnRH doesn't seem to have a critical impact on other life-sustaining systems such as the liver or kidneys.

Non-Surgical Sterilization Markets

New techniques were presented in terms of the markets they might best serve. Three markets have been identified for non-surgical sterilization drugs. These include Europe, the USA, and the Third World:

The European market tends to favor reversible sterilization.

The US market is oriented towards private animal healthcare and tends to favor permanent sterilization. There is also a need for cheap, one-dose permanent sterilization to help address stray and feral animals.

The Third World market needs cheap, permanent, low-tech sterilization to prevent human deaths from rabies.

Possible New Non-Surgical Sterilization Drugs

GnRH Agonist - This is a synthetic compound that the pituitary interprets to be GnRH. Its use overloads the pituitary's receptors so much that they become fatigued and less responsive. These drugs can cause a large increase in sex hormones immediately after treatment, but soon hormone levels drop dramatically for an extended period. Since the drug eventually wears off, it is considered a reversible form of sterilization.

Gonazon (azagly-nafarelin) is a GnRH agonist from a company called Intervet. It is pending approval in Europe for use as reversible contraception in female dogs. A slow-release implant injected under the skin delivers the drug. It has been shown to be effective in cats for 2-3 years after a single treatment, but treatment can be repeated annually. This drug has potential for use in males.

Suprelorin (deslorelin) is a GnRH agonist from Peptech Animal Health. It has been approved for two years in Australia and one year in New Zealand. This is a six month implant for males that is being tested for use in females. It is used for decreasing testosterone production in prostatic hyperplasia and other testosterone-sensitive conditions.

GnRH Antagonist - This class of drugs includes Decapeptides and Nonpeptides.

Decapeptides neutralize the effect of GnRH, or work against it. While this may seem preferable to the agonist approach, early drugs have caused some problems like allergic reactions. The basic chemical is also more expensive to manufacture and dosages required are much higher compared to the GnRH agonists leading to some technical difficulties with developing implants. Nevertheless, this will probably find niche use in things like pregnancy termination and possibly in chemical castration.

Nonpeptides are a very broad and promising class of drugs in human medicine, but there seems to be a possibility that they will not be effective in dogs.

GnRH Immunocontraceptive Vaccine

This drug make the animal allergic to his or her own GnRH, rendering it ineffective. It can cause permanent sterility with multiple injections. Researchers are currently working on single-shot permanent sterility.

GonaCon is a GnRH immunocontraceptive vaccine developed by the federal wildlife agency, NWRC, for use in white-tail deer. Approval by the Environmental Protection Agency is imminent. It is also being tested in feral cats. In cats, it causes testicular atrophy and 75 percent of a group of female cats were sterile 2.5 years after injection. It has caused some allergic reactions in dogs that were previously vaccinated for Leptospirosis. This drug is going into use very soon in wild animals. Note that the EPA controls drug approval for wildlife, and that includes feral cats. Approval for other companion animals would have to go through the FDA. This will take much longer and and the path to approval is more difficult. An extensive study is planned for GonaCon use in dogs in Brazil.

Chemical Acceleration of Ovarian Senescence (CAOS)

It has been discovered that a chemical plasticizer causes early "menopause" when injected in mice and dogs. A benefit of using this drug is that the erratic decline into ovarian senescence that causes undesirable symptoms in humans is avoided. The animal just transitions quickly to nonactive ovaries. No other side effects are known at this time.

Chemspay is a CAOS drug from Senestech. It is administered via a nanoparticle single injection delivery system. This product is not quite as close to market as some GnRH-related drugs but its nontoxicity and targeted, permanent effect are very promising.

Porcine Zona Pellucida Vaccine

This vaccine causes the body to have an allergic response to the outer covering of the egg. It seemed very promising when first discovered, but it just doesn’t seem to be practical for use in dogs and cats. It cannot be synthesized, which limits it to  non-commercial use. It does work well for horses and elephants and is being used in Africa to benignly control the elephant population. It could work for achieving the same goal with wild mustangs. The effect of treatment is seen in females only. It does cause ovarian damage and has no effect on reproductive behavior. (Treated animals still have heat cycles, but they don’t get pregnant).

Zinc Testicular Atrophy

This drug, previously marketed under the trade name Neutersol, is coming back under a licensing agreement with Abbott Laboratories. There is residual testosterone production in dogs treated with this drug. It is unknown whether the maker intends to do further studies of what this means in terms of dog behavior.

Conclusion

The list above is by no means exhaustive when it comes to the range of drug candidates under research. Other areas of research include LH and chorionic gonadotropin immunovaccines, progesterone receptor antagonists, genomics and proteonomics (which turn off genes by using small interfering RNA), GnRH-regulators Kisspeptin and GnIH. Many of these drugs are still in the basic research phase and are not likely to generate a marketable drug in the next decade. Still they reflect the extensive research currently under way in field of animal immunocontraception.

 

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