“The Next Weird Way We’re Changing Cats: What If You Could Make Your Cat Hypoallergenic With Biotechnology?”, 2021-11-05 ():
The first thing to know is that truly allergen-free cats are a myth. Sorry.
That’s because all cats—longhair, shorthair, no hair—shed a pernicious little protein called Fel d 1, found in the saliva and oil glands, which causes most cat allergies. Some cats shed 80× more of it than others of the same breed; no one knows why. Some shed more one month and less the next. Certain breeds may indeed make less Fel d 1 on average, but evidence is sparse. Back in the 2000s, a much-hyped start-up claiming to have bred hypoallergenic cats collapsed in disgrace, leaving some customers with pets that still made them wheeze and others who had shelled out thousands of dollars up front with no cat at all. That’s to say, demand for allergen-free cats is intense. It’s just that no one has managed to breed one.
Where old-fashioned breeding has failed, though, scientists are now turning to biotechnology. In recent years, a suite of sci-fi-esque strategies have been aimed at Fel d 1: a kibble coated in an egg-yolk derivative that neutralizes the allergen, a vaccine that uses cucumber mosaic virus to trick the cat’s immune system, and a gene therapy that deletes the Fel d 1 gene from cat DNA with the CRISPR editing technology [ et al 2022]. This kibble, in fact, is available on store shelves as Purina’s Pro Plan LiveClear cat food. The vaccine has already been tested on more than 100 cats. And although a viable gene therapy is much further off, scientists have managed to delete Fel d 1 from cat cells in a petri dish.
…To judge the potential harms of targeting Fel d 1, we also need a better understanding of the protein and exactly what it does in cats. Unfortunately, “nobody really knows the answer”, says Drew Weigner, a veterinarian in Atlanta who specializes in cats. Scientists have hypothesized that Fel d 1 may act like a pheromone for social signaling. That might mean it’s less important for house cats, especially ones that live solo. Male cats also tend to make more Fel d 1, and neutering them actually decreases their levels 3–5×—which means we’re already routinely altering cat’s Fel d 1 production. The high variability of allergen levels from cat to cat does suggest that reducing it shouldn’t have massive consequences. And indeed, the studies on cats fed with the anti-Fel d 1 kibble and those given the vaccine haven’t found adverse effects associated with reducing levels of the protein…She has found that the gene sequence of Fel d 1 varies tremendously from species to species—say, panther to lion—but also from cat to cat. The fact that it’s not being preserved over the course of evolution, Brackett says, suggests that “it may not be functionally essential for the cat.”
…Ebenezer Satyaraj, the director of molecular nutrition at Purina’s parent company, Nestlé, first began thinking about how to use cat food against Fel d 1 more than a decade ago. A key insight, he told me, was simply that cats spend a lot of time grooming themselves. Normally, this behavior spreads the Fel d 1 in their saliva all over their fur, which in turn gets all over your couch, your sweater, your bed, etc., etc., etc. But what if you could interrupt that process by feeding the cats something that neutralized the Fel d 1 in their mouth?
Satyaraj and his team landed on the idea of using anti-Fel d 1 proteins purified from egg yolk, which are made by injecting a hen with Fel d 1. Her immune system treats this Fel d 1 like a piece of a foreign pathogen, mounting antibodies that bind and neutralize it. These antibodies end up in egg yolks as a way of passing protection onto chicks. But they can also work, remarkably, as a kind of interspecies immunity transfer: There is a pig-feed additive, for example, made with the egg-yolk antibodies meant to protect against E. coli. In this case, Satyaraj wanted the egg-yolk antibodies to neutralize Fel d 1 on the cats—ultimately, co-opting a chicken’s immune system to protect allergic humans.
It worked. The egg-yolk coating on Purina’s cat food reduces the amount of allergen shed by 47% on average. The goal here, Satyaraj says, is to bring Fel d 1 levels down below a threshold to minimize allergy symptoms—it might not be enough for everyone, but it should be enough for some. A study in allergic humans found that using Purina’s cat chow did help decrease congestion and itchy eyes [cf. et al 2019a/ et al 2019b/ et al 2020/ et al 2021]. How well the kibble works will depend on how much Fel d 1 a cat starts with and how sensitive the owner is to even tiny amounts of the allergen. And any effect lasts only as long as you keep feeding them Purina’s food.
A second idea to make cats more hypoallergenic involves harnessing the power of the cat’s own immune system, where the effects might last longer. In 2013, scientists at the University of Zurich founded a company, now called Saiba Animal Health, to make a vaccine for cats that reduces shedding of Fel d 1. They used a multipart strategy originally developed for human vaccines: Hide the Fel d 1 protein inside the shell of a cucumber mosaic virus, which is in turn embedded with a bit of tetanus toxin. This tricks the cat’s immune system into thinking Fel d 1 is part of a virus, says Gary Jennings, the chief operating officer of Saiba. Once immunized, the cat starts making antibodies that neutralize Fel d 1. Their allergen levels indeed dropped over several weeks, and Saiba found that the allergic cat owners were able to spend more time petting their vaccinated cats. The company has since licensed the technology to a large animal-health company—whose name Jennings says he can’t disclose—to gather the data necessary for regulatory approval.
Both the human doctors and the vets I spoke with thought such a vaccine would exist in an interesting liminal space: Was a vaccine given to cats in order to treat humans considered an animal vaccine or a human vaccine? Who would even regulate it? Jennings told me that, based on conversations with the FDA and the European Medicines Agency, both would oversee it as an animal vaccine—but slightly differently. The FDA needs to make sure that the vaccine does not harm cats and works for humans, but the European Medicines Agency wants to weigh the harm and the benefit to the cat itself.
But scientists have also come a long way already. Indoor Biotechnologies’ president and CEO, Martin Chapman, was part of the original team that first isolated the gene for Fel d 1, back in the 1990s. Even then, he says he remembers thinking, Wouldn’t it be great if we could delete these genes? But it wasn’t possible with the technology of the time.