Dog may have life extended by science in the future – 11/28/2023 – Science

A pet dog’s life has a predictable trajectory. Over time, the floppy-eared puppy who falls asleep in his food bowl will grow into a long-legged teenager with an insatiable interest in squirrels — before finally settling into adulthood as a canine creature of habit, with a carefully chosen location. bedtime and a well-rehearsed greeting ritual.

But as the years pass, their joints will become stiff and their muzzle will turn gray. And one day, which will inevitably come too soon, your wagging tail will finally calm down.

“When you adopt a dog, you are adopting future heartbreak,” said Emilie Adams, a New Yorker who owns three Rhodesian Ridgebacks. “It’s worth it over time because you get so much love…But their lives are shorter than ours.”

In recent years, scientists have been looking for medications that can prevent this heart pain, prolonging the lives of our canine companions.

This Tuesday (28), the biotechnology company Loyal announced that it took another step to offer one of these medicines. “The data provided is sufficient to show that there is a reasonable expectation of efficacy,” an FDA representative told the company in a recent letter. (Loyal provided a copy of the letter to The New York Times.)

This means the drug, which Loyal declined to identify for proprietary reasons, met one of the requirements for “extended conditional approval,” a type of authorization granted to veterinary medicines that target unmet health needs and require trials. difficult clinicians.

The drug is not available to pet owners, and the FDA has yet to review the company’s safety and manufacturing data.

The conditional approval, which Loyal expects to receive in 2026, will allow the company to commercialize it even before a large clinical trial is completed.

“We will aim for at least a year of healthy life extension,” said Celine Halioua, founder and CEO of Loyal.

Whether the drug will actually deliver on this promise remains to be seen. Although a small study suggests that LOY-001 may mitigate metabolic changes associated with aging, Loyal has not yet demonstrated that it extends the lifespan of dogs.

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

More drugs of the day are in development. A team of researchers is conducting a canine clinical trial of rapamycin, which has been shown to extend the life of mice in the laboratory. And loyal itself is recruiting dogs for a clinical trial of another drug, LOY-002.

These cases signal both the rapid pace of science and the seriousness with which researchers and regulators are approaching a field that once seemed like science fiction.

They also raise questions about what it might mean to succeed, said Daniel Promislow, a biogerontologist at the University of Washington and co-director of the Dog Aging Project, which is leading the rapamycin clinical trial.

“What if it works?” he said. “What are the implications?”

Fountain of Youth

Aging may be inevitable, but it is not inflexible. Scientists have already created longer-living worms, flies and mice by tweaking aging-related genes.

These discoveries have raised the tantalizing possibility that scientists might find drugs that have the same life-extending effects in people. This remains an active area of ​​research, but canine longevity has recently begun to attract more attention, in part because dogs are good models for human aging and in part because many pet owners would love to have more time with their pets.

Investigational drugs work in different ways. Rapamycin, which has also generated intense interest as a possible 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% of dog owners whose pets received the drug reported improvements in health or behavior, including increased activity or playfulness, compared with 8% 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 linked to aging and longevity in several species; in dogs, it is known to play a key role in determining body size. Although the idea has not yet been proven, some scientists hypothesize that high levels of IGF-1 drive both rapid growth and accelerated aging in large dogs, which generally have a shorter lifespan than their small counterparts.

Loyal’s own research, which has not yet been published, suggests that LOY-001 reduces IGF-1 levels in dogs and that it may counter aging-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 a pretty exciting approach,” said Colin Selman, an aging biogerontologist at the University of Glasgow who was not involved in the research and did not review the company’s data.

But proving that a drug can actually extend dogs’ lives will require large, time-consuming clinical trials. While some are underway, it will be at least a few more years before the results are known. And regardless of the drug, researchers will need to demonstrate that it adds good, healthy years to a dog’s life rather than just prolonging its decline, experts said.

Canine Dilemmas

It’s too early to say how much the longevity drugs will cost, but Halioua estimates LOY-001 would cost “tens of dollars a month.”

For some owners, cost won’t be a deterrent, said Karen Cornelius of Illinois, who has had mastiffs and other “giant” breeds for decades. Many died around the age of nine, said Cornelius, who runs several Facebook groups for owners of giant dogs.

“It was just a discussion on one of my forums yesterday about how short their lives were and how people would give anything to be able to extend it,” she said.

Some experts are concerned that this enthusiasm could be exploited, particularly if the drugs are advertised as sources of canine youth, while questions of long-term safety and effectiveness remain unresolved. They noted that dogs themselves cannot give consent.

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

LOY-001’s worst side effect has been mild, temporary gastrointestinal discomfort, Halioua said, although she acknowledged that the safety criteria would be “extremely, extremely, extremely high.”

Longevity medications are intended for healthy dogs, which changes the risk-benefit calculation. “It’s one thing if a dog is on the verge of death and you’re giving him last-minute treatment,” said Bev Klingensmith, a Great Dane breeder in Iowa who also has a Great Dane and a golden retriever. “Giving my young, healthy dog ​​a new medication would seem a little scary.”

Even medicines 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 that are worth living?” said Anne Quain, a veterinarian and veterinary ethicist at the University of Sydney, in an email. “What if we see more dogs outliving their owners?”

Reforming breeding practices that have contributed to life-shortening health problems for many dogs and expanding access to basic veterinary care may be a better way to improve dogs’ lives, she added. “We can save many ‘dog years’ by ensuring that as many dogs as possible have access to this care.”