More Than One Way to Fix Cat Allergy

Ingrid Hein

June 08, 2020

There is new hope for cat lovers who are allergic to their pets. Rather than desensitizing the human, researchers are working to eliminate the Fel d 1 protein, the primary allergen, from the cat, using CRISPR-Cas9 gene-editing technology.

"One of the benefits of CRISPR, compared to other methods of tackling this problem, is that you can permanently remove Fel d 1, compared with other techniques that only reduce the allergen," said Nicole Brackett, PhD, from Indoor Biotechnologies.

Previous attempts to remove the allergen have included feeding cats a specially formulated food that reduces Fel d 1 in the saliva, so less ends up on the dander when they lick themselves, as reported by Medscape Medical News.

"We hope to get to a point where we can offer an injection, or a series of injections, you would get at the vet, which would make the cat allergen-free," said Brackett, who presented the research in a poster at the European Academy of Allergy and Clinical Immunology 2020 Digital Congress.

When you're using this kind of technology, you are taking on a tremendous amount of responsibility.

About 10% of humans are allergic to cats, and we see the ones who are affected by their own cats, said Dean Mitchell, MD, an allergist and immunologist from Mitchell Medical Group in New York City.

"This research is interesting, but when you're using this kind of technology, you are taking on a tremendous amount of responsibility," he told Medscape Medical News.

"It's really an exciting technology, but I think it's scary, altering genes," he said. "You never know what you're going to change. Maybe we should use it to cure COVID first."

Identifying the Target

For their study, Brackett and her colleagues used discarded tissue samples from 50 spayed and neutered cats to collect genomic DNA from the Fel d 1 chains 1 and 2.

The first goal was to see how similar genes were between cats, she explained. "We wanted to target a region in the gene that is well conserved — something you would see in all cats — not a random mutation."

The researchers were able to sequence a panel of 10 guide RNAs and use CRISPR Cas-9 to edit the genes. "We now have proof of principle in a cat cell line," Brackett told Medscape Medical News.

We still have a long way to go, but should have something we can test in a cat in a couple of years. But, she acknowledged, "we still don't know the role of the protein in the cat."

Fel d 1 expression differs from cat to cat, Brackett pointed out. "Some cats have an abundance and some have very little. The expression can vary, even within one cat."

Speculation on the function of Fel d 1 also varies. Because it's produced in the sebaceous gland, "it may serve as a way to coat, or protect, the skin. Or maybe it has something to do with chemical communication, maybe to communicate with other cats," she said. "But the fact that we see so much Fel d 1 variability with no obvious correlating behaviors makes us think it's not essential. One of the benefits of our study is we may figure that out."

Her lab is also looking at Fel d 1 expression in wild cats to determine its origin from an evolutionary standpoint. "We are curious to see how this allergen has evolved in different species of cats," she explained.

Desensitizing Humans

Cat allergies "rank number two in frequency and seriousness of allergies after food allergies, causing people to need to be on steroids or medications," Mitchell told Medscape Medical News. "Fifty percent of my immunotherapy practice is cat or dog allergy; it's a significant problem."

Young kids can't play at their friend's houses, relationships are affected, and families have to choose between their beloved cat and a healthy family member, he said.

Sublingual immunotherapy of Fel d 1 has been proven effective in clinical trials and is common in Europe, but "only about 100 allergists in the United States offer it," Mitchell said. "It's been a very underappreciated therapy, and I really don't know why; maybe because it's not patentable by a drug company."

Sublingual drops are not covered by insurance, and the therapy runs about $120 per month in the United States. "I've helped hundreds of patients with it," said Mitchell, and usually the therapy significantly improves patient quality of life.

The fact is, people make major life choices based on their cats, Mitchell explained.

One of his pollen-allergic patients who loved both her cat and her cat-allergic boyfriend told him that her boyfriend wouldn't sleep over. "Can you help him?" she asked.

"The first day I see him, he's wheezing and can't breathe." Mitchell recalled. He treated the boyfriend with sublingual Fel d 1 immunotherapy. "After 4 or 5 months, he could go over to her house using inhalers on weekends sometimes. A year later, they moved in together and got married. The cat even slept on the bed at the end.”

Mitchell discharged the boyfriend after 3 years of treatment. He ran into him on a New York sidewalk a couple of years later and asked how he was doing. It turned out the couple had gotten divorced.

"That's too bad, I told him. But at least you don't have to deal with the cat anymore," Mitchell recalled.

"Oh no, I liked the cat too much, he stayed with me," his patient told him.

Mitchell laughed. "You just can't make this stuff up!"

Brackett works for Indoor Biotechnologies as a scientist. Mitchell has disclosed no relevant financial relationships.

European Academy of Allergy and Clinical Immunology (EAACI) 2020 Digital Congress

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