The Race to Deliver the Hypoallergenic Cat
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Allergies outlook NILS JACOBI/GETTY Scientists are working on a feline vaccine that could block the protein most commonly associated with allergic reactions to cats. The race to deliver the hypoallergenic cat Researchers are looking beyond allergen immunotherapy to help people whose pets make them sneeze. By Amber Dance octor, if you tell me to get rid Hospital in Madrid. Up to 30% of people show Some researchers are trying to improve of the cat, I’m getting rid of sensitivity to cats in some regions. this immunotherapy, and others are trying my kids first,” said the parent The effects can be limited to sniffles and a different angle by injecting Fel d 1 antibod- of one young patient with sneezes for some people. For others, how- ies into people with allergies. Scientists are an allergy to the family pet. ever, the allergy can prompt dangerous also seeking ways to neutralize Fel d 1 before “DSandra Gawchik, an allergist in Chester, Penn- asthma attacks. A US study estimated that, it leaves the animal — or even stop cats from sylvania, knew they were only half-joking — among cat-sensitive people, 47% of emergency producing it entirely. she had heard similar threats before. Another hospital visits could be attributed to feline patient recounted being pushed out of the exposure1. And allergy is among the main rea- Sticky stuff house by his wife and daughter over his cat sons why owners send cats to shelters. Cats secrete the Fel d 1 protein from their allergy, saying they preferred the feline to him. Small doses of cat allergens — the major one salivary and sebaceous glands, and spread it Sensitivity to pets (cat and dog allergies being a small, sticky protein called Fel d 1 — throughout their fur during regular tongue occur at similar rates) is typically the second can help to build up tolerance over time. But baths. Released in shed skin and hair, it floats in most prevalent allergy in any region, after pol- treatments can cost US$800–1,000 annually, the air for hours, attaching to carpets, curtains len or mites, says Joaquin Sastre, an allergist require up to 100 injections over 3–5 years, and and clothing. Some cat owners with allergy at the Jiménez Díaz Foundation University are not always permanent or wholly effective. concerns invest substantial time in cleansing Nature | Vol 588 | 3 December 2020 | S7 ©2020 Spri nger Nature Li mited. All rights reserved. Allergies outlook not only their houses but also their pets; weekly immunotherapy and a monthly infusion response, they will not build up tolerance. But however, the protein is difficult to eradicate. of antibodies against TSLP. Regeneron aims to circumvent this issue by dos- “You’d have to bathe the cat every other day,” “We hope to induce a state of tolerance that ing people directly with Fel d 1 IgG antibodies. says Gawchik. And because Fel d 1 sticks to would potentially occur more quickly, last The treatment is based on two IgG antibodies cat owners’ clothing, it can show up in places longer and reach a higher level,” says principal that cover up key IgE binding sites on either end where no feline has ever set paw. investigator Jonathan Corren, an allergist and of the allergen. Together, they can block up to Fel d 1’s tiny dimensions also make it a tricky immunologist at the University of California, 83% of the IgE–Fel d 1 interactions responsible customer. At less than one-tenth the size of Los Angeles. The group plans to publish its for most allergic reactions to cats. In a phase Ib a single ribosome, it can slip deep into the findings soon. “The results, at this point, do test, people with a cat allergy received a single lungs and trigger asthma, alongside itchy look promising,” Corren says. dose of the antibody combination4. Then, in eyes and nasal congestion. Despite these dif- The antibody therapy would be costly, four tests conducted between eight days and ficulties, however, cat allergy could be seen Corren adds, so would be best suited for nearly three months later, researchers sprayed as a low-hanging fruit for allergy researchers. people with severe allergies or asthma. But it cat hair extract into the participants’ nostrils. Although at least eight different cat proteins needn’t be restricted to those sensitive to cats. Symptoms dropped in 60% of participants, by can cause allergy, Fel d 1 is by far the major con- “The approach should be applicable to any an average of 60%, Orengo says. Regeneron is tributor. Tamping down a person’s response to number of allergens,” he says. now running a phase II trial. just this one protein, or reducing the presence Adiga Life Sciences in Huntingdon, UK, is The advantage of the antibodies, says of Fel d 1 in the cat and its environment, could trying a different approach, substituting Fel d 1 Orengo, is that they will work more quickly minimize symptoms across a wide swathe of for Cat-PAD, which consists of smaller, syn- than immunotherapies that require the patient feline-sensitive people. Unlike in dogs, which thetic peptides based on Fel d 1. The hope is to build tolerance. However, because the produce several key allergens, scientists need that a synthetic allergen would be less likely to patient will not be producing the antibodies only hit the bullseye once in cats. cause a reaction and could therefore be given themselves, regular boosters will be required, People who are allergic to Fel d 1 react by in higher doses — potentially enabling people perhaps quarterly. The team is also working on creating immunoglobulin E (IgE) antibodies. to achieve tolerance in just four treatments. a similar treatment against birch pollen, and These induce mast cells to spew out histamine In a phase II trial, 11 participants who received is considering other allergens, too. and other chemicals that create sneezing, itch- Cat-PAD saw their symptoms reduced for up to “This is certainly an interesting approach,” ing and congestion. A less unpleasant response 2 years2. But a 2016 phase III study failed when says Martin Bachmann, an immunologist at the to the protein would be one involving IgG anti- people receiving a placebo developed just as University of Bern. “But it’s probably going to bodies — the type made in response to viruses much tolerance to Fel d 1 as did those on the be kind of expensive.” — which are not generally associated with aller- immunotherapy. Mark Larché, an immunol- gic reactions. People who had cats as children ogist at McMaster University in Hamilton, Immune to the allergen and who have an overall lower risk of allergy Canada, and a consultant for the company, Bachmann is among the scientists who are tend to develop this kind of response, notes speculates that part of the problem might have targeting Fel d 1 in cats themselves. If the ani- Martin Chapman, chief executive of Indoor been that all the phase III participants had to mals did not produce the protein, this should Biotechnologies in Charlottesville, Virginia, be cat owners. As a result, even those in the prevent allergic reactions in most people. which specializes in products and laboratory placebo group would have daily exposure to But researchers are unsure how thoroughly services linked to indoor air quality, allergies Fel d 1, potentially promoting tolerance. the protein needs to be eliminated to have the and asthma. desired effect, as well as what happens to a cat Current immunotherapy for allergies trains “We hope to induce a state without Fel d 1. the body to make IgG antibodies that grab anti- No one knows what Fel d 1 does for felines. gens before IgE can lock on. The injections of tolerance that would Some cats have a little and some have a lot, so contain purified cat allergens, or a broader potentially last longer and large amounts don’t seem to be necessary. And mix of cat proteins. Overall, immunotherapy reach a higher level.” the cat’s breed doesn’t seem to make much is up to 70% effective, says Gawchik, but it only difference; even hairless Sphynx cats make works “if the patient religiously gets shots, on Fel d 1. On average, unneutered males have a weekly basis”, and some people return for Adiga is now planning a trial with non-cat- the most and females the least, suggesting booster injections years later because their owners. Larché says that participants will be the protein might carry hormones or phero- allergies have returned. Sastre says that nearly tested for allergy symptoms by sending them mones. But it has also been hypothesized to one-third of his patients still need some form to cat cafes (theme cafes where patrons can protect cats’ skin. of anti-allergy medication, such as antihista- watch or play with cats). The company is also In 2013, Bachmann co-founded HypoPet, mines, to keep their symptoms in check. And in pursuing peptide-based immunotherapy for a spin-off company from the University of some cases, the small doses of allergen cause allergies to grass3 and dust mites, Larché says, Zurich in Switzerland. The firm aims to cre- the very reactions they are meant to stifle. That and has designed peptides for birch allergy — a ate hypoallergenic cats by vaccinating them is why researchers see room for improvement. common problem in northern Europe and the against their own Fel d 1, so that the cat’s IgG The Immune Tolerance Network, a collab- northeastern United States. antibodies block the protein before it is sniffed oration funded by the US National Institute All of these immunotherapies ultimately rely up by a human.