Gene therapy could control cat population

Eighty percent of the world’s 600 million domestic cats are strays and subject to poor living conditions, and they pose a threat to other wildlife. Female cats have traditionally been spayed in a bid to control the size of the population. But could an injected gene therapy shot in which a virus is used to deliver a hormone that stops the ovary from producing eggs be a much more effective alternative. I’ve been speaking to researchers David Pepin and, kicking off, Bill Swanson...

Bill - We have a problem with overpopulation of both dogs and cats in the world. And for cats, we estimate that there's more than 600 million of them and 80% of those animals, they're free living animals, so they tend to have pretty short lives. And there's a huge animal welfare issue with those animals getting diseases and being hit by automobiles. From a conservation perspective, they kill a lot of wild birds and wild prey. They have major impacts on wildlife populations. The primary way that we address that now is through surgical sterilisation, and that requires the intervention of veterinarians. It requires surgical facilities and it's very expensive and labour intensive. So the goal here was to come up with a method of sterilising cats that did not require surgery.

Chris - And your coworker, David, has been part of this as well. What was the approach you've taken, David?

David - So my laboratory has been interested in studying this female reproductive hormone called anti mullerian hormone or AMH. And one of the discoveries we've made is, if you raise the levels of this hormone, you can produce contraception. And so we developed a number of tools including a gene therapy approach that we had initially studied in mice and rats. And we thought this may be a tool that could work to control the cat population. And so we started working with Bill to try to apply these findings to the cat.

Chris - How does the technique work? What does this anti mullerian hormone do? Why does it work as a contraceptive? And why was the leap between rodents then into cats? Normally cats chase mice, but this is the other way around?

David - Anti mullerian hormone is actually a natural hormone produced by the ovary and it's normal function is to regulate the development of follicles in the ovary. And by raising the levels of this hormone, we can suppress the growth of follicles in the maturation stage. And if we raise it high enough, we can actually more or less stop follicles from developing in the rodents. And so now we try to apply this to cats and to do so we developed a gene therapy approach, which is basically using a virus to deliver the gene, encoding AMH, and then the virus infects muscle cells and those muscle cells will then produce the protein secreted into the blood and raise that level in circulation up to the contraceptive threshold.

Chris - And did you get high levels of this produced for a long time? Because obviously the goal of contraception is it's got to work for a long time, otherwise eventually you'll be back to square one.

David - Right, and that's the beauty of gene therapy is that you can, in one injection, transduce cells and coax them into producing this hormone for a very long time. In our case, we're still following these cats four years in and they're still expressing their hormone.

Chris - So it sounds like it's working, Bill.

Bill - Yeah, the paper describes the results from our main study, which involved nine cats. And so we treated six of those cats with the gene therapy that delivered the AMH gene to produce that protein. And then we had three control cats in that study, and we found that they did produce very high AMH levels and it did have some impact on fertility.

Chris - In what way? What was the outcome?

Bill - Well, the main outcome was that the cats were not ovulating. And obviously if you don't ovulate, you can't have an egg to be fertilized. And then the cats are contraceptive for as long as that protein is elevated.

Chris - And David, did this play out the way you had anticipated in the cats? When you look at the expression from your gene therapy of the signal that you're putting in the AMH, does this continue to be expressed the way you had hoped? Were there any side effects? Were the cats otherwise well?

David - In mice we could reach very high levels, and that obviously could last the lifetime of a mouse, but the lifetime of a mouse is very short. It's about a year or two. In cats we need to get production for much longer than this. But in the way it was given, which is intramuscularly, and then, following the concentration in the blood, it was very similar between the two species. In both cases, the injection was well tolerated. There was no adverse events. We saw no signs of toxicity. And so we were very encouraged by the safety of the approach.

Chris - And one always wonders when you've got people building gene therapy vectors with viruses, about environmental safety (is there any risks that the cats could then transmit this to other vulnerable cats species we want to preserve and conserve in the world and render them infertile by accident) but also, does it have any other knock on effects for the physiology of the cat? Are they otherwise okay?

大卫,所以这是一个非常重要的一点。的病毒传染s that we use is an Adeno-associated virus, which is non replicative, which means that, following infection, no new particles are made, it doesn't make any new virus. So it can't spread from cat to cat or even to the wild to other species. Also, the genome that's delivered by this virus doesn't integrate. That means it never gets into the DNA of the cat. So there are some inherent safety mechanisms based on the virus that we use.

Chris - And Bill, does this mean then that the next step is to try this and do this on a broad scale, not just in domestic animals in a very constrained circumstance, but test this on real feral animals and see if you are able to achieve long-term suppression of fertility?

比尔-是的,我我们的主要资金来源s the Michelson Found Animal Foundation, and they're meeting with the Food and Drug Administration this month to really talk about the path forward to get this approved as a veterinary product. And that's going to require a lot more data. So we're going to have to do probably larger studies involving more cats to verify the safety and efficacy that we saw in our study.