Can Biotechnology Take the Allergies Out of Cats?
From a special food to a vaccine and gene editing, new technologies may offer solutions for cat lovers with allergies.
Amy Bitterman, who teaches at Rutgers Law School in Newark, gets enormous pleasure from her three mixed-breed rescue cats, Spike, Dee, and Lucy. To manage her chronically stuffy nose, three times a week she takes Allegra D, which combines the antihistamine fexofenadine with the decongestant pseudoephedrine. Amy's dog allergy is rougher--so severe that when her sister launched a business, Pet Care By Susan, from their home in Edison, New Jersey, they knew Susan would have to move elsewhere before she could board dogs. Amy has tried to visit their brother, who owns a Labrador Retriever, taking Allegra D beforehand. But she began sneezing, and then developed watery eyes and phlegm in her chest.
"It gets harder and harder to breathe," she says.
Animal lovers have long dreamed of "hypo-allergenic" cats and dogs. Although to date, there is no such thing, biotechnology is beginning to provide solutions for cat-lovers. Cats are a simpler challenge than dogs. Dog allergies involve as many as seven proteins. But up to 95 percent of people who have cat allergies--estimated at 10 to 30 percent of the population in North America and Europe--react to one protein, Fel d1. Interestingly, cats don't seem to need Fel d1. There are cats who don't produce much Fel d1 and have no known health problems.
The current technologies fight Fel d1 in ingenious ways. Nestle Purina reached the market first with a cat food, Pro Plan LiveClear, launched in the U.S. a year and a half ago. It contains Fel d1 antibodies from eggs that in effect neutralize the protein. HypoCat, a vaccine for cats, induces them to create neutralizing antibodies to their own Fel d1. It may be available in the United States by 2024, says Gary Jennings, chief executive officer of Saiba Animal Health, a University of Zurich spin-off. Another approach, using the gene-editing tool CRISPR to create a medication that would splice out Fel d1 genes in particular tissues, is the furthest from fruition.
"Our goal was to ensure that whatever we do has no negative impact on the cat."
Customer demand is high. "We already have a steady stream of allergic cat owners contacting us desperate to have access to the vaccine or participate in the testing program," Jennings said. "There is a major unmet medical need."
More than a third of Americans own a cat (while half own a dog), and pet ownership is rising. With more Americans living alone, pets may be just the right amount of company. But the number of Americans with asthma increases every year. Of that group, some 20 to 30 percent have pet allergies that could trigger a possibly deadly attack. It is not clear how many pets end up in shelters because their owners could no longer manage allergies. Instead, allergists commonly report that their patients won't give up a beloved companion.
No one can completely avoid Fel d1, which clings to clothing and lands everywhere cat-owners go, even in schools and new homes never occupied by cats. Myths among cat-lovers may lead them to underestimate their own level of risk. Short hair doesn't help: the length of cat hair doesn't affect the production of Fel d1. Bathing your cat will likely upset it and accomplish little. Washing cuts the amount on its skin and fur only for two days. In one study, researchers measured the Fel d1 in the ambient air in a small chamber occupied by a cat—and then washed the cat. Three hours later, with the cat in the chamber again, the measurable Fel d1 in the air was lower. But this benefit was gone after 24 hours.
For years, the best option has been shots for people that prompt protective antibodies. Bitterman received dog and cat allergy injections twice a week as a child. However, these treatments require up to 100 injections over three to five years, and, as in her case, the effect may be partial or wear off. Even if you do opt for shots, treating the cat also makes sense, since you could protect more than one allergic member of your household and any allergic visitors as well.
An Allergy-Neutralizing Diet
Cats produce much of their Fel d1 in their saliva, which then spreads it to their fur when they groom, observed Nestle Purina immunologist Ebenezer Satyaraj. He realized that this made saliva—and therefore a cat's mouth--an unusually effective site for change. Hens exposed to Fel d1 produce their own antibodies, which survive in their eggs. The team coated LiveClear food with a powder form of these eggs; once in a cat's mouth, the chicken antibody binds to the Fel d1 in the cat's saliva, neutralizing it.
The results are partial: In a study with 105 cats, the level of active Fel d1 in their fur had dropped on average by 47 percent after ten weeks eating LiveClear. Cats that produced more Fel d1 at baseline had a more robust response, with a drop of up to 71 percent. A safety study found no effects on cats after six months on the diet. "Our goal was to ensure that whatever we do has no negative impact on the cat," Satyaraj said. Might a dogfood that minimizes dog allergens be on the way? "There is some early work," he said.
A Vaccine
This is a year when vaccines changed the lives of billions. Saiba's vaccine, HypoCat, delivers recombinant Fel d1 and the coat from a plant virus (the Cucumber mosaic virus) without any vital genetic information. The viral coat serves as a carrier. A cat would need shots once or twice a year to produce antibodies that neutralize Fel d1.
HypoCat works much like any vaccine, with the twist that the enemy is the cat's own protein. Is that safe? Saiba's team has followed 70 cats treated with the vaccine over two years and they remain healthy. Again the active Fel d1 doesn't disappear but diminishes. The team asked 10 people with cat allergies to report on their symptoms when they pet their vaccinated cats. Eight of them could pet their cat for nearly a half hour before their symptoms began, compared with an average of 17 minutes before the vaccine.
Jennings hopes to develop a HypoDog shot with a similar approach. However, the goal would be to target four or five proteins in one vaccine, and that increases the risk of hurting the dog. In the meantime, allergic dog-lovers considering an expensive breeder dog might think again: Independent research does not support the idea that any breed of dog produces less dander in the home. In fact, one well-designed study found that Spanish water dogs, Airedales, poodles and Labradoodles--breeds touted as hypo-allergenic--had significantly more of the most common allergen on their coat than an ordinary Lab and the control group.
Gene Editing
One day you might be able to bring your cat to the vet once a year for an injection that would modify specific tissues so they wouldn't produce Fel d1.
Nicole Brackett, a postdoctoral scientist at Viriginia-based Indoor Biotechnologies, which specializes in manufacturing biologics for allergy and asthma, most recently has used CRISPR to identify Fel d1 genetic sequences in cells from 50 domestic cats and 24 exotic ones. She learned that the sequences vary substantially from one cat to the next. This discovery, she says, backs up the observations that Fel d1 doesn't have a vital purpose.
The next step will be a CRISPR knockout of the relevant genes in cells from feline salivary glands, a prime source of Fel d1. Although the company is considering using CRISPR to edit the genes in a cat embryo and possibly produce a Fel d1-free cat, designer cats won't be its ultimate product. Instead, the company aims to produce injections that could treat any cat.
Reducing pet allergens at home could have a compound benefit, Indoor Biotechnologies founder Martin Chapman, an immunologist, notes: "When you dampen down the response to one allergen, you could also dampen it down to multiple allergens." As allergies become more common around the world, that's especially good news.
Saliva May Help Diagnose PTSD in Veterans
A recent study finds that former soldiers with post traumatic stress disorders have a certain set of bacteria in their saliva, a distinct signature that is believed to be the first biological marker for PTSD.
As a bioinformatician and young veteran, Guy Shapira welcomed the opportunity to help with conducting a study to determine if saliva can reveal if war veterans have post-traumatic stress disorder, or PTSD.
The research team, which drew mostly from Tel Aviv University’s Sackler Faculty of Medicine and Sagol School of Neuroscience, collected saliva samples from approximately 200 veterans who suffered psychological trauma stemming from the years they spent fighting in the First Lebanon War in 1982. The researchers also characterized the participants’ psychological, social and medical conditions, including a detailed analysis of their microbiomes.
They found that the former soldiers with PTSD have a certain set of bacteria in their saliva, a distinct microbiotic signature that is believed to be the first biological marker for PTSD. The finding suggests that, in the future, saliva tests could be used to help identify this disorder. As of now, PTSD is often challenging to diagnose.
Shapira, a Ph.D. student at Tel Aviv University, was responsible for examining genetic and health-related data of the veterans who participated – information that had been compiled steadily over four decades. The veterans provided this data voluntarily, Shapira says, at least partly because the study carries important implications for their own psychological health.
The research was led by Illana Gozes, professor emerita of clinical biochemistry. “We looked at the bacteria in their blood and their saliva,” Gozes explains. To discover the microbial signatures, they analyzed the biometric data for each soldier individually and as a group. Comparing the results of the participants’ microbial distribution to the results of their psychological examinations and their responses to personal welfare questionnaires, the researchers learned that veterans with PTSD – and, more generally, those with significant mental health issues – have the same bacterial content in their saliva.
“Having empirical metrics to assess whether or not someone has PTSD can help veterans who make their case to the Army to get reparations,” Shapira says.
More research is required to support this finding, published in July in Nature’s prestigious Molecular Psychiatry, but it could have important implications for identifying people with PTSD. Currently, it can be diagnosed only through psychological and behavioral symptoms such as flashbacks, nightmares, sleep disorders, increased irritability and physical aggressiveness. Veterans sometimes don’t report these symptoms to health providers or realize they’re related to the trauma they experienced during combat.
The researchers also identified a correlation that indicates people with a higher level of education show a lower occurrence of the microbiotic signature linked to PTSD, while people who experienced greater exposure to air pollution show a higher occurrence of this signature. That confirms their finding that the veterans’ health is dependent on their individual biology combined with the conditions of their environment.
“Thanks to this study, it may be possible in the future to use objective molecular and biological characteristics to distinguish PTSD sufferers, taking into account environmental influences,” Gozes said in an article in Israel21c. “We hope that this new discovery and the microbial signatures described in this study might promote easier diagnosis of post-traumatic stress in soldiers so they can receive appropriate treatment.”
Gozes added that roughly a third of the subjects in their study hadn’t been diagnosed with PTSD previously. That meant they had never received any support from Israel’s Ministry of Defense or other officials for treatment and reparations, the payments to compensate for injuries sustained during war.
Shapira’s motivation to participate in this study is personal as well as professional: in addition to being veteran himself, his father served in the First Lebanon War. “Fortunately, he did not develop any PTSD, despite being shot in the foot...some of his friends died, so it wasn’t easy on him,” says Shapira.
“Having empirical metrics to assess whether or not someone has PTSD can help veterans who make their case to the Army to get reparations,” Shapira says. “It is a very difficult and demanding process, so the more empirical metrics we have to assess PTSD, the less people will have to suffer in these committees and unending examinations that are mostly pitched against the veterans because the state is trying to avoid spending too much money.”
The Friday Five Weekly Roundup in Health Research
In this week's Friday Five, the right facial expression for your mental health. Plus, can virtual reality reduce pain? Lab made blood vessels. Gene editing muscles to lower blood sugar. And a magic ingredient coming from exhaust vents.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- The right facial expression for your mental health
- Can virtual reality reduce pain?
- Lab made blood vessels
- Gene editing muscles to lower blood sugar
- A magic ingredient coming from exhaust vents