In the early 1990s, an overgrown shaggy schlub named Beethoven won the hearts of millions of children with a pair of theatrical films, “Beethoven” (1992) and “Beethoven’s 2nd” (1993). The real-life Beethoven tragically died shortly after filming the sequel, inadvertently raising awareness of how St. Bernards and other large-breed dogs such as Great Danes, Newfoundlands, and Mastiffs tend to shorten their life spans by only 7-10 years. Conversely, shorter dog breeds (if healthy) can survive about twice as long.
“We hope that one day we can translate similar treatments we’ve learned about longevity in dogs to humans.”
But what if there was a way to extend the lifespan of these large breed dogs? One company is aiming for just that. San Francisco-based startup Loyal is a clinical-stage veterinary company that recently made headlines for seeking conditional approval of a new drug from the US Food and Drug Administration (FDA). (Yep, the same government agency responsible for regulating human drugs does the same for animals.) The company is part of Cellular Longevity, a biotech company that develops drugs aimed at extending the lives of not only dogs, but also humans.
In the meantime, Loyal is seeking approval from the FDA for 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 respond to Salon’s question about what they are. But based on what they’ve shared, LOY-001 appears to reduce a growth-promoting hormone in dogs called IGF-1 and, in the process, extend the lifespan of these animals. If it becomes available by Loyal’s target year of 2026, dogs given LOY-001 will receive vaccinations every three to six months once they reach seven years of age and weigh more than 40 pounds.
It has already been established that IGF-1 levels are associated with longevity and aging in mice, nematodes and fruit flies. Since large dogs often have up to 28 times more IGF-1 than small dogs, it makes sense that LOY-001 could extend the lifespan of large breeds using the same principles that have been applied to other animals, although the overall evidence remains unclear. .
“Anyone with a large-breed dog is faced with this dire calculation of their dog’s shortened life expectancy,” Celine Halioua, founder and CEO of Loyal, told Salon via email. “We don’t accept this. It is [25 million] large breed dogs in the US alone – that’s 25 million dogs we can help live longer and with a better quality of life.”
As with all animal research, this kind of research can raise ethical concerns, says Adam Boyko, a Cornell University professor who directs the Canine Genetics Laboratory and co-founded the canine DNA testing company Embark Veterinarya.
“The main ethical concern I see here is to make sure that experimental drugs are used judiciously and can reasonably be expected to have a positive cost-benefit for the dogs in the study,” Boyko said. In addition to protecting the dogs in the research itself, pet dogs receiving their first vaccinations must also be protected—which means owners must be told that the drug is experimental and will be updated as new information becomes available.
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“The LOY-001 drug focuses on repairing the damage caused by years and years of selective human breeding.”
“Experimental drugs and clinical trials are common in pets, so I don’t think the thoughtful and properly implemented introduction of drugs is necessarily a concern, but ensuring low risk is important because these drugs are being administered to healthy dogs,” Boyko explained. He also noted that because drugs like LOY-001 can interfere with human aging as well as aging in dogs, dogs are at risk of exploitation unless drug companies and the medical community exercise transparency.
“One could see the company possibly continuing to market a drug that showed some promise in reversing the aging clock but also showed some unacceptable risks to some dogs because they were interested in generating more data to improve potential human treatments,” Boyko argued. “So transparency is really important so owners can make informed decisions about what’s best for their dog.”
When Salon asked Halioua about the ethical concerns that arise in drug trials like the one with LOY-001, he said that Loyal prioritizes safety and efficacy.
“We all have a responsibility to do the right thing by dogs – we feed and shelter them and take care of their health,” Halioua explained. “We give them medicine when they are sick. Our products follow this same principle – supporting the quality of life of dogs in their middle years so that they can stay healthy as they age and thus live longer and better lives.”
Halioua also noted that the company’s mission is actually to reverse the human-caused form of dog cruelty.
“The LOY-001 drug focuses on repairing the damage caused by years and years of selective human breeding,” Halioua noted. “This is clearly beneficial for dogs.”
At the same time, Halioua admitted that Boyko’s understanding of LOY-001’s effects on human aging is correct. Despite this, Halioua emphasized that the company’s primary goal is to help large breed dogs. His further observation was that “it is also true that dogs are an excellent model for human aging. We live in the same environments and share similar lifestyles. We have similar age-related diseases for the same reasons. Because of this, we hope to someday be able to translate what we learn about canine longevity into similar as a form of treatment aimed at people.”
The long-term effects of LOY-001 need not only benefit humans. After all, if the lives of large breed dogs and humans could be extended with medication, why not extend the lives of non-large breed dogs?
“Yes – we are already working on this drug,” Halioua told Salon. “We currently have three drugs in development. LOY-001 and LOY-003 are aimed at 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 non-large breed dogs benefiting from research conducted by companies like Loyal.
“While LOY-001 targets insulin growth factor signaling (a key factor in both body size and reduced longevity in large breed dogs), other antiaging drugs target different pathways and are more likely to work in all dogs,” Boyko told Salon. “Experiments with some of these drugs in laboratory animals have been impressive, so there is reason to believe that they would also be successful if properly administered to pets and even humans.”
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