A new drug for extending the lifespan of dogs by one year is closer to reality. What if it works? – The Irish Times

The life of a pet dog follows a predictable trajectory. Over time, the floppy-eared puppy that keeps falling asleep in his food bowl will become a lanky-legged adolescent with an insatiable interest in squirrels – before eventually settling into adulthood as a canine creature of habit, with a carefully chosen napping location and a well-rehearsed greeting ritual.

But as the years progress, his joints will stiffen and his muzzle will grey. And one day, which will inevitably arrive too soon, his wagging tail will finally still.

“When you adopt a dog, you’re adopting future heartbreak,” says Emilie Adams, a New Yorker who owns three Rhodesian Ridgebacks. “It’s worth it over time because you just have so much love between now and when they go. But their lifespans are shorter than ours.”

In recent years, scientists have been chasing after drugs that might stave off this heartbreak by extending the lives of our canine companions. On Tuesday, the biotech company Loyal announced that it had moved one step closer to bringing one such drug to market. “The data you provided are sufficient to show that there is a reasonable expectation of effectiveness,” an official at the US Food and Drug Administration (FDA) informed the company in a recent letter. (Loyal provided a copy of the letter to the New York Times.)

That means that the drug, which Loyal declined to identify for proprietary reasons, has met one of the requirements for “expanded conditional approval,” a fast-tracked authorisation for animal drugs that fulfil unmet health needs and require difficult clinical trials. The drug is not available to pet owners yet, and the FDA must still review the company’s safety and manufacturing data. But conditional approval, which Loyal hopes to receive in 2026, would allow the company to begin marketing the drug for canine life extension, even before a large clinical trial is complete.

“We’re going to be going for claiming at least one year of healthy lifespan extension,” says Celine Halioua, the founder and chief executive of Loyal.

Whether the drug will actually deliver on that promise is unknown. Although a small study suggests LOY-001 might blunt metabolic changes associated with ageing, Loyal has not yet demonstrated that it lengthens dogs’ lives.

But the letter, which came after years of discussion between Loyal and the FDA, suggests that the agency is open to canine longevity drugs, Halioua says.

More are in the pipeline. A team of academic researchers is conducting a canine clinical trial of rapamycin, which has been shown to extend the lives of lab mice. And Loyal is recruiting dogs for a clinical trial of another drug candidate, dubbed LOY-002.

These developments are a sign of the accelerating pace of the science and the seriousness with which researchers and regulators are taking a field that once seemed like science fiction. They also raise questions about what it might mean to succeed, says Daniel Promislow, a biogerontologist at the University of Washington and a codirector of the Dog Aging Project, which is conducting the rapamycin trial.

“What if it works?” Promislow says. “What are the implications?”

Ageing may be an inevitability, but it is not an unyielding one. Scientists have created longer-lived worms, flies and mice by tweaking key ageing-related genes.

These findings have raised the tantalising possibility that scientists might be able to find drugs that have the same life-extending effects in people. That remains an active area of research, but canine longevity has recently started to attract more attention, in part because dogs are good models for human ageing and because many pet owners would love more time with their furry family members.

“There’s not a lot you wouldn’t do if you could stack the deck in your favour to preserve the life of your hairy, four-legged child,” says Adams, the Rhodesian Ridgeback owner.

The drugs under investigation act in different ways. Rapamycin, which has also attracted intense interest as a potential longevity drug for humans, inhibits a protein known as mTOR, which regulates cell growth and metabolism.

This year, a team of scientists including Promislow and some of his colleagues at the Dog Aging Project published an analysis of dogs that had been randomly assigned to receive either a low dose of rapamycin or a placebo for six months. Although the sample size was small, 27 per cent of dog owners whose pets received the drug reported improvements in health or behaviour, including increases in activity or playfulness, compared with 8 per cent of owners whose dogs received a placebo.

LOY-001, an extended-release implant intended for large, adult dogs, is designed to modulate a different growth-related compound: insulin growth factor-1, or IGF-1. The IGF-1 pathway has been associated with ageing and longevity in several species; in dogs, it is known to play a key role in determining body size. Although the idea remains unproven, some scientists hypothesise that high IGF-1 levels drive both rapid growth and accelerated ageing in large dogs, which generally have shorter lifespans than small ones.

Loyal’s own research, which has not yet been published, suggests that LOY-001 does reduce IGF-1 levels in dogs and that it might curb ageing-related increases in insulin; an observational study of nearly 500 dogs also suggested that lower insulin levels were correlated with reduced frailty and a higher quality of life.

“It’s quite an exciting approach,” says Colin Selman, a biogerontologist of ageing at the University of Glasgow, who was not involved in the research and has not personally reviewed the company’s data.

But proving that a drug can actually extend canine lives will require large, time-consuming clinical trials. Although some are under way, it will be at least several more years before the results are in. And regardless of the drug, researchers will need to demonstrate that it adds good, healthy years to a dog’s life, rather than just drawing out their decline, experts say.

“If it proves true that it extends lifespan, I’m only interested in that if the period of life that is extended is good quality life,” says Dr Kate Creevy, a veterinarian at Texas A&M and the chief veterinary officer of the Dog Aging Project. “I don’t want to make my dog live an extra two years in poor health.”

It is too soon to say what longevity drugs will cost, but Halioua predicts that LOY-001 would work out to “mid-double-digit dollars per month”.

For some owners, cost will not be a deterrent, says Karen Cornelius of Illinois, who has owned mastiffs and other “giant” breeds for decades. Many died when they were about nine years old, says Cornelius, who runs several Facebook groups for owners of giant dogs.

“We were just having a discussion on one of my forums yesterday about how short-lived they were, and how people would give almost anything if they could extend that life,” she says.

Some ethicists worry that this enthusiasm could be exploited, especially if the drugs are advertised as fountains of canine youth while questions of long-term safety and efficacy remain unresolved. The dogs themselves cannot give consent, some researchers have noted.

“Is it in their best interest to live a little bit longer when there’s some risk to taking these drugs?” says Rebecca Walker, a philosopher and bioethicist at the University of North Carolina at Chapel Hill, who says she would not give a longevity drug to her golden retriever. “Or is it really in the best interest of their owners, who are very attached to them?”

The worst side effect of LOY-001 has been mild and temporary gastrointestinal distress, Halioua says, although she acknowledges that the bar for safety would be “extremely, extremely, extremely high”.

Longevity drugs are intended for healthy dogs, which changes the risk-benefit calculus. “It’s one thing if a dog is on death’s door and you’re giving them some late-breaking treatment,” says Bev Klingensmith, a great dane breeder in Iowa who also has a great dane and a golden retriever of her own. “Giving my young, healthy dog a brand-new drug would seem a little scary.”

Even drugs that deliver on all their promises will raise ethical questions. “If animals are living longer, do we have the resources and commitment to provide lives worth living?” Dr Anne Quain, a veterinarian and an expert on veterinary ethics at the University of Sydney, says in an email. “What if we see more dogs outliving their owners?”

Reforming the breeding practices that have contributed to life-shortening health problems in many dogs and expanding access to basic veterinary care might be a better way to improve canine lives, she adds. “We can save many ‘dog years’ by ensuring that as many dogs have access to that care as possible,” Dr Quain says.

While scientists gather more data on potential longevity drugs, there are steps that dog owners can now take to foster healthier ageing, experts say, including keeping their dogs lean and providing ample exercise and mental stimulation.

Halioua admits to having a soft spot for senior dogs. “They just want a nice bed to sleep on,” she says, as her elderly Rottweiler, Della, naps. Della, who has lymphoma and dementia, is not on LOY-001 because enrolling her in the company’s studies would present a conflict of interest, Halioua says, adding that the dog seems happy.

Ultimately, even if scientists can delay a pet owner’s heartbreak, they are unlikely to prevent it altogether. “These are definitely not immortality or radical life-span-extension drugs,” Halioua says in an email.

“Nothing we are developing could make a dog live forever.” – This article originally appeared in the New York Times.