Dr. Christina McRae 288

Photo by Michael Lawrence

Shown here at home with her one-eyed cat, Pecabo, Dr. Christina McRae has seen the toll on cats of allergies. She worked in shelters and saw many cats surrendered by allergic owners.

Apart from allergists, small animal veterinarians probably field more questions from allergic cat owners than any other health care practitioners. Owners want to know whether they can alleviate their own allergies by doing things such as spritzing the fur with a special spray; giving cats low doses of the tranquilizer acepromazine; adding Brewer's yeast to its food; removing the animal's anal sacs; buying naturally or specially-bred "hypoallergenic" cats; and more.

Veterinarians often discourage such strategies, which have limited to no proven benefit. While keeping the home clear of fur and dander can help those with mild allergies, there currently is no such thing as allergy-proofing a cat.

That could change soon. There are at least three interventions, all based on somehow modifying the cat, that aim to neutralize or eliminate the principal allergen produced by cats: 

• Food: Nestlé Purina Pet Care Co. began this month selling a kibble designed to make cats less allergenic.
• Vaccine: A biotechnology company in Switzerland is working on shots for the cat.
• Gene editing: A U.S. company based in Virginia is exploring the use of technology known as CRISPR to stop cats from producing a key allergen.

Target: Fel d 1

In people with allergies, the immune system mistakes a foreign substance, sometimes called an antigen, for something harmful, and starts making antibodies to fight it. Those antibodies cause allergy symptoms such as itching, runny nose and watery eyes. The phenomenon is known as the antigen-antibody reaction.

Cat allergies are estimated to occur in about 10% of the population worldwide. Treatment options for sufferers include antihistamines, decongestants and nasal steroids. Some endure a battery of injections of small amounts of an allergen for a year or more to train their immune systems to be less sensitive to cats, in a form of immunotherapy or desensitization.

Ten cat allergens have been identified as causing reactions in humans. The main culprit is a protein called Fel d 1, which is produced by salivary, sebaceous (in the skin), perianal (in the anal sacs) and lacrimal (in the eye) glands. The name is derived from the source organism's genus name, Fel d for Felis domesticus, and 1 indicating the chronology of its discovery, based on a nomenclature approved by the World Health Organization ⁄ International Union of Immunological Societies. Fel d 1 was registered with WHO/IUIS in 2003.

During grooming, cats spread Fel d 1 onto their hair and skin, which they shed along with fur and invisible dander. Because of its small size and low weight, Fel d 1 can float in the air for long periods, and readily adheres to surfaces such as sweaters, blankets and carpeting. For this reason, some allergists recommend rehoming the pet as the most expedient solution.

"Most doctors say, 'Get rid of the cat,' " said Dr. Christina McRae, a veterinarian in Ontario, Canada, who has worked in shelters and seen the outcome firsthand. "You get a lot of animals surrendered because of allergies."

Her clients, however, don't like giving up their cats. She understands. McRae herself is allergic to cats, lives with a cat and owned a feline practice for 20 years. She's had allergy shots, and still, at times, turns to antihistamines and nose sprays to quell bad reactions. She washes her hands frequently and avoids things that trigger her allergy, such as perfume.

"It is certainly something that really limits people's enjoyment of their pet," she said. Her allergies are less severe these days but at one time, they made her sick more often. Still, she did not give up cats. "I always tell people, if I was allergic to my husband, I wouldn't get rid of him," she said.

McRae recommends to pet owners simple interventions, including avoiding scented litters, and wiping down the cat's coat regularly. Beyond that, she suggests they see an allergist and not take giving up the cat for an answer.

You shed what you eat

Nestlé Purina, one of the largest pet food makers in the world, has for 10 years been investigating ways to reduce allergens in cat hair and dander through the cat's diet, according to Janette Artea, a public relations representative for the company. Purina Pro Plan LiveClear diet is the culmination of those efforts.

The principle behind the diet, laid out in a paper by researchers at Purina and published last year in the Journal of Feline Medicine and Surgery, is to use the antigen-antibody interaction to deactivate some of the Fel d 1 by binding it to antibodies derived from chicken eggs. According to a monograph by Purina, the approach does not stop the cat from producing Fel d 1. Instead, it transforms the Fel d 1 in saliva into a compound the human immune system doesn't react to.

The key ingredient in LiveClear binds to the Fel d 1 allergen in cats’ saliva in the cat’s mouth as it chews, Artea explained in an email to the VIN News Service. "It is important to feed LiveClear every day as 'free choice' throughout the day, or serve the daily feeding amount split into two to three meals, rather than as just a single feeding only at mealtime, to continue to neutralize the allergen as it is produced," she explained.

In a trial involving 11 cats treated with the food, Fel d 1 levels in the saliva of nine decreased by at least 20%. One cat showed an increase. (By comparison, Fel d 1 levels went up in five controls and down in three.)

Is the novel ingredient in the diet safe for cats? To test safety, Purina for six months fed 42 cats differing levels of the antibody proteins, including levels many times greater than the amount in the Pro Plan LiveClear diet. In a paper published in Frontiers in Veterinary Science, the authors reported no significant differences between the control and test groups in clinical observations, body weights, food consumption, serum chemistry, hematology, blood coagulation, urinalyses, and mortality and morbidity checks.

Some veterinarians and nutritionists question, in general, how much diet safety can be determined from short-term feeding trials. (The U.S. Food and Drug Administration, which regulates pet food, does not require feeding trials at all.)

Dr. Hillary Israeli, a small animal veterinarian in Pennsylvania, pointed out that it took a while for potential problems to emerge in grain-free diets. The FDA announced last year it was looking into a possible connection between grain-free diets and a heart condition, dilated cardiomyopathy, in dogs. 

Asked about the new diet from Purina, Israeli said, "There's nobody who currently has a cat who has an urgent medical need to use this food. Why would you want your cat to be the test market?"

No formal studies have been done to examine whether cat-allergic people living with cats fed the LiveClear diet experienced a corresponding reduction of symptoms. 

"Purina's research and development primarily focused on the pet food ingredient in cat food and its benefits to the cat," Artea said. "We've also received positive, anecdotal feedback from consumers who have tested the product by feeding it to their pets."

How any intervention focused on deactivating or eliminating Fel d 1 will affect human allergies is an open question.

Dr. Jack Becker, an allergist in Ardmore, Pennsylvania, said, "At the moment, I don't have a test to tell the patient how they would do," he said. When he tests for cat allergies, Fel d 1 is just one of multiple Fel d allergens in the test. 

Some will do better; some will have fewer symptoms; and some it won't help at all, Becker said. In addition, if you take Fel d 1 out of the home, a person could develop another sensitivity to another cat allergen in its place.

"We aren't smart enough yet to know why someone becomes allergic to any particular allergen, so we can't predict if eliminating one allergen just won't be replaced with another," he said. 

Purina began selling the LiveClear diet through veterinary clinics, pet specialty and online retailers last week. It's not cheap. The suggested retail price is $7.68/pound. For comparison, the suggested retail price of Purina Pro Plan Savor diet is $4.28/pound.

A twist on a vaccine

HypoPet AG, a Swiss biotechnology company, aims to flip the treatment script. The company spun off from the University of Zurich seven years ago to develop a vaccine for cats. If successful, it could offer an alternative to an extended course of desensitizing shots for allergic owners.

As in the new Purina diet, the vaccine dubbed HypoCat uses the antigen-antibody interaction to neutralize Fel d 1. Whereas the diet incorporates antibody proteins derived from chicken eggs, the vaccine aims to stimulate the cat to produce its own antibodies. According to a paper published last year in The Journal of Allergy and Clinical Immunology, the vaccine consists of recombinant Fel d 1 and a proprietary virus-like plant particle derived from the cucumber mosaic virus that contains inactivated tetanus toxin. The toxin is an immunogenic molecule that stimulates a long-lasting immune response to Fel d 1.

In four studies involving 54 cats, the vaccine induced anti-Fel d 1 antibodies. The paper's authors reported a reduction in the cats' allergen levels and reduced allergenicity in the cats' tears. They said the vaccine was "well tolerated and had no overt toxic effect." They also said that in the future, they would not use an adjuvant, a substance added to vaccines to boost immune response. Some veterinarians avoid adjuvanted vaccines in cats due to concerns about injection-site sarcomas.

HypoPet also has completed a field study following 10 cat-allergic owners living with vaccinated cats for between six months and one year. The results, published in the journal Viruses, reported that pet owners with cats that had received three HypoCat vaccines (given in three-week intervals) noticed a reduction in their allergic symptoms and were able to spend more time with their cats before the onset of symptoms.

HypoPet CEO and COO Gary Jennings described the study as exploratory and promising. The important correlation, he said, is that when the cat's antibody titers were up, the human's symptoms were down.

The promising result may not be enough to persuade all pet owners — and their veterinarians — to order the treatment.

If the vaccine is safe for cats and reduces allergic reactions for humans, McRae wonders if owners will want to subject their cat to shots for what is essentially a human health condition. "Most people don't even want to take their cat to the vet," she said.

HypoCat is being developed through a collaboration with Benchmark Holdings, a veterinary biotechnology company in the United Kingdom, and researchers at HypoPet, the Latvian Biomedical Research and Study Centre in Riga, and the veterinary school and genomics center at the University of Zurich. Speaking from Zurich today, Jennings said the COVID-19 pandemic is causing indefinite delays in the development of the vaccine. But, he added, future studies would include focusing on the benefits of the vaccine to the cat.

"One can postulate many advantages" to cat health of reducing its allergenicity, he said. As an example, he said, it could mean "spending more time with your cat [and consequently], you are better able to monitor its health status." Other possibilities he listed: It could lead to regular teeth-brushing for cats, more opportunities for socialization, fewer restrictions on a cat's movements, and generally less stress in the home.

Gene editing could go a step further

Indoor Biotechnologies (InBio) in Charlottesville, Virginia, is taking a different tack. The company is investigating how it might use gene-editing to "knock out" the two genes that code for Fel d 1 "with the ultimate goal of having an allergen-free cat," said Nicole Brackett, a postdoctoral scientist who has been heading up the gene-editing project for 18 months.

The company has been around for decades, focused on manufacturing biologics for allergies and asthma. It makes tests that measure cat, dog, dust mite, cockroach, mold, and pollen allergens in the environment. InBio tests also measure the potency of Fel d 1 in allergenic extracts used in immunotherapy. Both Purina and HypoPet relied on InBio tests in their research for the allergen-reducing diet and vaccine.

Company founder and CEO Dr. Martin D. Chapman said that when Fel d 1 was identified, researchers understood that reducing or eliminating it could make a big difference for people with allergies. "When CRISPR came along, it was pretty self-evident that this would be a great application," he said. CRISPR stands for clustered regularly interspaced short palindromic repeats. Chapman was formerly professor of medicine and microbiology at the University of Virginia and a member of the university's Asthma and Allergic Diseases Center.

A biological gene-editing tool based on the antiviral defense systems of bacteria, CRISPR can target and remove, add or alter short sections of DNA. InBio's goal is to remove the DNA that instructs a cat's cells how to produce Fel d 1.

"As of right now, we have proof of principle of the CRISPR editing in … an immortalized cat cell line in a petri dish," Brackett said.

The CRISPR approach differs from the vaccine and the diet in that it proposes permanently to alter the physiology of a cat. Chapman said the No. 1 question about the approach has been: How will it affect the animal?

The role of Fel d 1 in cat biology has not been determined, according to researchers working on all three interventions. Hypotheses include that the protein plays a role in protecting the skin or in pheromone/chemical signaling.

"It's difficult to answer the question [of what difference it will make] without doing the actual experiment, which is to do the deletion," Chapman said.

"When you do delete genes, the animals develop compensatory mechanisms or actually replace that function somehow," Chapman said. "It's very unusual, actually I would say, in gene therapy for you to delete something and then for the animal to just die."

Still ahead is testing the gene-editing process in specific cat tissues that express the protein, such as salivary glands; and in embryos before approaching what Chapman called the "whole animal."

For that stage, there remains a significant obstacle: how to get the gene editor into the patient. It's an issue that CRISPR scientists are working on, independent of InBio.

One delivery route may be to infect an animal with a benign virus that contains CRISPR.

In a first-ever, doctors at Oregon Health & Science University in March injected CRISPR directly into a person, via their eye, to correct a genetic condition that causes blindness.

Chapman imagines a scenario where veterinarians might do something similar to a cat to alleviate allergies in the cat owner.

"In the same way you'd take your cat to get it neutered or spayed or whatever, if you wanted to convert it to being an allergen-free cat then [the veterinarian] would give it an injection of a gene-editing material," he said.

Bigger picture

In addition to unanswered questions about safety and effectiveness, these new interventions raise other issues for some veterinarians.

"I sit and ponder the ethics of treating my cats to treat my problem," Israeli said. The Pennsylvania veterinarian has contended with severe cat allergies for most of her life. She has endured monthly allergy shots for going on 15 years to deal with her sensitivity. She still sometimes relies on antihistamines and for a few patients needs to wear gloves and a mask to complete an exam.

She wonders why in a world populated by so many incredible organisms, people want to remake a particular animal. "I have a cat. I'm not changing my cat; I'm treating myself."

While not endorsing any of the new or pending approaches, McRae sees them as an extension of business as usual. "When you think of it: Most of our job is making the cat more agreeable to the human lifestyle," she said. In that context, a cat vaccine or gene-editing might not be a bridge too far.

For cat-allergic veterinarians, such as Israeli and McRae, treatments targeting individual cats won't help them much in their workplace. Nor do they take aim at the broader public health challenge.

In a study of pet danders in the environment, Dr. Daniel O. Morris, a professor of dermatology and allergy at the University of Pennsylvania School of Veterinary Medicine, found that cat allergens were so easily spread, their impact is felt well beyond their home turf.

"Exposure to pet danders occurs in public spaces at high enough concentrations to elicit allergic reactions in some people with asthma," Morris pointed out in an email to VIN News. "So, it's not always just about the cat you live with."

This story has been changed to clarify Janette Artea's role. Artea is not a Purina employee but works for a public relations company that represents Purina.