In the early 1990s, an overgrown shaggy schlub of a St. Bernard named Beethoven won the hearts of millions of children with a pair of hit theatrical movies, the titularly titled "Beethoven" (1992) and "Beethoven's 2nd" (1993). Tragically, the real-life Beethoven died shortly after the sequel was filmed, thereby inadvertently raising awareness about how St. Bernards and other large-breed dogs like Great Danes, Newfoundlands and Mastiffs tend to have shortened life spans of only 7 to 10 years. By contrast, shorter dog breeds (if healthy) can survive for roughly twice as long.
Yet what if there was a way to extend the lifespan of these large-breed dogs? One company aims to do just that. The San Francisco-based startup Loyal is a clinical-stage veterinary medicine company that recently made headlines for working to receive conditional approval for a new medicine from the United States Food and Drug Administration (FDA). (Yep, the same government agency responsible for regulating human pharmaceuticals does likewise for animals.) The company is part of Cellular Longevity, a biotech firm developing drugs that aim to extend the lifespan of not just canines, but one day humans as well.
In the meantime, Loyal is on track to petition the FDA for approval of three drugs: LOY-001, LOY-002 and LOY-003. The company has not yet released the actual chemical names of these drugs and did not answer Salon's question about what they are. But based on what they have shared, LOY-001 seems to reduce a growth-promoting hormone in dogs called IGF-1, and in the process increases the life expectancy of these animals. If it becomes available by Loyal's target year of 2026, dogs who are administered LOY-001 will receive shots every three to six months once they reach the age of seven and are over 40 pounds.
It has already been established that IGF-1 levels are linked to longevity and aging in mice, roundworms and fruit flies. Because large dogs often have as much as 28 times as much IGF-1 as smaller dogs, it makes sense that LOY-001 could extend large-breed life expectancies through the same principles that have applied to other animals, although the overall evidence remains unclear.
"Everyone with a large-breed dog faces this awful calculation around their dog’s reduced life expectancy," Celine Halioua, the founder and CEO of Loyal, told Salon by email. "We don’t accept this. There are [25 million] large-breed dogs in the US alone — that’s 25 million dogs we can help live longer, and with better quality of life."
As with anything involving animal research, a study like this one can raise ethical concerns, according to Adam Boyko, a Cornell University professor who runs a canine genetics lab and co-founded the dog DNA testing company Embark Veterinary.
"The main ethical concern I see here is ensuring the experimental drugs are being used judiciously with a reasonable expectation of a positive cost-benefit to the dogs enrolled in the study," Boyko said. In addition to protecting the dogs in the study itself, the pet dogs who receive those first shots also need to be protected — which means owners must be informed that the medicine is experimental and updated as new information comes in.
"Experimental drugs and clinical trials are common in pets, so I don’t think there’s necessarily a concern with a prudent and properly conducted rollout of the drugs, but ensuring low risk is key since these drugs are being given to healthy dogs," Boyko explained. He also observed that — because drugs like LOY-001 could address human aging as well as dog aging — dogs will be at risk of exploitation unless the pharmaceutical companies and medical community practice transparency.
"One could see a company potentially continuing to market a drug that showed some promise at reversing the aging clock but also showed some unacceptable risks to some dogs because of their interest in generating more data to better inform potential human therapies," Boyko argued. "Thus, transparency really is key so owners can make informed decisions about what is best for their dog."
When Salon asked Halioua about the ethical concerns that arise in drug trials like those with LOY-001, she replied that Loyal prioritizes safety and effectiveness.
"We all have a responsibility to do right by dogs — we feed and shelter them and take care of their health," Halioua explained. "We give them medications when they’re sick. Our products follow this same principle — supporting dogs’ quality of life in their middle years so they stay healthy as they age and consequently live longer, better lives."
Halioua also pointed out that the company's mission actually reverses a form of human-caused cruelty to dogs.
"LOY-001 drug is focused on undoing the damage introduced by years and years of selective breeding by humans," Halioua pointed out. "This is unambiguously beneficial to dogs."
At the same time, Halioua acknowledged that Boyko's perception about the implications of LOY-001 for human aging are correct. That said, Halioua emphasized that the company's priority is to help large-breed dogs. Her additional observation was that "it’s also true that dogs are an excellent model for aging in humans. We live in the same environments and share similar lifestyles. We face similar age-associated diseases for the same reasons. Because of this we hope to someday be able to translate what we learn about longevity in dogs into similar therapies for humans."
The long-term implications of LOY-001 do not have to only benefit humans. After all, if large-breed dog lifespans and human lifespans could be extended by pharmaceuticals, why not extend the lifespans of dogs that do not belong to large breeds?
"Yes — we are already working on that drug," Halioua told Salon. "We have three drugs in development currently. LOY-001 and LOY-003 are focused on large-breed dogs. And our LOY-002 drug is designed for senior dogs of all but the smallest breeds."
Boyko shared Halioua's optimism about dogs that are not part of large breeds benefiting from the research being performed by companies like Loyal.
"While LOY-001 is focused on insulin growth factor signaling (which is a key driver of both body size and decreased longevity in large breed dogs), other anti-aging drugs target different pathways and would be more likely to work in all dogs," Boyko told Salon. "The trials with some these drugs in laboratory animals have been impressive so there is reason to believe they would also be successful if properly administered to pets and even humans."
