ER VET

BIO:

Dr. Brennen McKenzie is Director of Veterinary Medicine for Loyal, a San Francisco-based biotechnology company researching aging and therapies to improve lifespan and healthspan in dogs. In addition to his work at Loyal, he has been in practice as a small animal veterinarian for more than twenty years. Dr. McKenzie attended the School of Veterinary Medicine at the University of Pennsylvania. He has served as President of the Evidence-Based Veterinary Medicine Association, lectured on evidence-based medicine at numerous veterinary conferences, and published journal articles in the fields of evidence-based medicine and small animal geroscience. While working as a practitioner, speaking, and writing, Dr. McKenzie has continued to pursue post-graduate training, and in 2015 he completed his MSc in Epidemiology at the London School of Hygiene and Tropical Medicine in 2015.

Transcript:

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Announcer: This is Pet Life Radio.

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Dr. Justine Lee: Welcome to ER Vet on Pet Life Radio.

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Dr. Justine Lee: I'm your host, Dr.

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Dr. Justine Lee: Justine Lee, and I'm an emergency critical care veterinary specialist and a toxicologist.

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Dr. Justine Lee: Thanks for joining us.

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Dr. Justine Lee: Today, we're gonna be talking about a cool, amazing new update about how to make your dog live longer, and what dog owner doesn't want their pet to live longer, so you wanna tune in right after these messages.

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Dr. Justine Lee: Welcome back to ER Vet on Pet Life Radio.

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Dr. Justine Lee: I'm Dr.

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Dr. Justine Lee: Justine Lee, and I'm super excited to speak with Dr.

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Dr. Justine Lee: Brennen McKenzie, who's a fellow veterinary colleague.

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Dr. Justine Lee: Brennen, thank you so much for joining us today.

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Dr. Brennen McKenzie: Thank you, my pleasure.

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Dr. Justine Lee: All right, just so our audience knows a little bit about you, do you mind just explaining who you are, where you're trained and what you do now?

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Dr. Brennen McKenzie: Absolutely.

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Dr. Brennen McKenzie: So I am one foot in two worlds.

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Dr. Brennen McKenzie: I am in clinical practice as a general practitioner.

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Dr. Brennen McKenzie: I trained at the University of Pennsylvania more years ago than I care to say.

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Dr. Brennen McKenzie: And I've been in practice in private practice for that entire time.

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Dr. Brennen McKenzie: But about five years ago, I started working as Director of Veterinary Medicine for Loyal.

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Dr. Brennen McKenzie: Loyal is a biotechnology startup company based in San Francisco.

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Dr. Brennen McKenzie: And our goal is to develop FDA approved medications to extend healthy lifespan in dogs.

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Dr. Brennen McKenzie: So I'm getting to work both in the clinical and in the research world.

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Dr. Justine Lee: Awesome.

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Dr. Justine Lee: Well, I really appreciate you joining us today.

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Dr. Justine Lee: And I love the stuff that Loyal is starting to do.

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Dr. Justine Lee: So thank you for all that you do, first of all.

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Dr. Justine Lee: Now, I want to talk to you about the health span and the lifespan in dogs.

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Dr. Justine Lee: First of all, what exactly is the definition of health span and how is it related to lifespan in dogs?

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Dr. Brennen McKenzie: So lifespan is a word and a concept that everyone's very familiar with.

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Dr. Brennen McKenzie: It's simply the amount of time that an individual's been alive.

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Dr. Brennen McKenzie: Health span is a pretty simple, but less commonly known term that refers to the length of time that an individual has been healthy and functional with a good quality of life.

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Dr. Brennen McKenzie: So lifespan and health span are both aspects of the length of time, but health span refers specifically to health.

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Dr. Brennen McKenzie: And the relationship in dogs is particularly interesting because of course, we know that the vast majority of our companion dogs don't pass away from a specific disease.

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Dr. Brennen McKenzie: We euthanize them when their quality of life has reached a point that we feel is unacceptable.

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Dr. Brennen McKenzie: And the ability to extend health span by delaying the onset of age-associated diseases is also the ability to extend life span because if dogs are healthier and have a good quality of life, then they will naturally live longer.

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Dr. Justine Lee: Sounds like it's important for human medicine too, but that's a whole nother topic.

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Dr. Justine Lee: Now, what are some approaches for extending life span and health span in dogs?

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Dr. Justine Lee: And what role could drugs play in accomplishing this?

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Dr. Brennen McKenzie: So there are a number of things that we can already do to extend the healthy lifespan of our dogs.

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Dr. Brennen McKenzie: And these are things that as a clinician, I talk to dog owners about all the time, things like preventative veterinary care.

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Dr. Brennen McKenzie: There's evidence that dogs who see their veterinarian regularly who keep up with vaccinations and parasite prevention and with screening for diseases live longer.

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Dr. Brennen McKenzie: So simply continuing with good quality preventative care is an important thing that dog owners can do to extend the healthy lifespan in their dogs.

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Dr. Brennen McKenzie: We also know that one of the most challenging problems right now in canine medicine is obesity.

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Dr. Brennen McKenzie: We know that dogs who are overweight have a shorter life expectancy than dogs who are a healthy weight.

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Dr. Brennen McKenzie: So maintaining your dog at a healthy body weight is an important way of extending lifespan and healthspan.

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Dr. Brennen McKenzie: However, what we're interested in is giving veterinarians and dog owners more tools to do that.

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Dr. Brennen McKenzie: More tools to prevent the development of age-associated disease and keep dogs happy and healthy longer.

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Dr. Brennen McKenzie: And we think that medications can play a role in that.

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Dr. Brennen McKenzie: I'll give you an example.

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Dr. Brennen McKenzie: One of the most effective ways to extend healthy lifespan in a variety of species, which has been tested in dogs, is something called calorie restriction.

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Dr. Brennen McKenzie: Purina did a great study a while back where they paired up puppies, Labrador Retriever puppies.

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Dr. Brennen McKenzie: And one dog was in a group that was fed its entire life to a healthy, normal body condition.

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Dr. Brennen McKenzie: The puppy that was matched was fed to 25% fewer calories than that group.

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Dr. Brennen McKenzie: So all they did for these dogs was, some of them got fed to be a healthy condition and some of them got fed less.

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Dr. Brennen McKenzie: The dogs who were calorie restricted lived on average a year and a half longer.

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Dr. Brennen McKenzie: They developed all of the same age-related problems that Labradors are prone to, but they were generally getting these problems a year, two years, sometimes three years later on average.

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Dr. Brennen McKenzie: So we know that calorie restriction is a way that you can extend healthy lifespan.

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Dr. Brennen McKenzie: The problem is that it's not a practical, realistic thing to do for our companion dogs.

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Dr. Brennen McKenzie: Food is love, food is how we show affection, and trying to get people to dramatically restrict how they feed their dogs is likely to interfere with the human-animal bond.

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Dr. Brennen McKenzie: And if it's not done carefully with proper supervision, it's likely to cause malnutrition and actually be harmful.

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Dr. Brennen McKenzie: However, what we've learned from studies like this is that there are underlying mechanisms of aging that occur that we can manipulate.

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Dr. Brennen McKenzie: So if calorie restriction can change aging and let dogs live longer and healthier lives, perhaps we can target some of those same mechanisms with medications and give another tool to owners that is more practical and more realistic to use to achieve the same outcome.

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Dr. Justine Lee: I love all that you're bringing up, and thank you so much for bringing up that Purina study.

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Dr. Justine Lee: It's one of my favorite long-term studies, and I'm hoping one day they replicate this in cats, but it's probably very similar, right?

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Dr. Justine Lee: We know there's a huge link between obesity and the development of osteoarthritis.

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Dr. Justine Lee: We know that obesity definitely contributes to underlying cardiopulmonary problems, heart and lung problems, to creating arthritis, to really affecting the mobility of dogs and cats as they age.

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Dr. Justine Lee: I can't tell you how heartbreaking it is for me as an emergency veterinary specialist, where I have to euthanize dogs that come in on a gurney, and it's because they're usually older, obese Labradors who can't get up because they have such severe osteoarthritis that was worsened by obesity.

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Dr. Justine Lee: And oftentimes when I'm talking to pet owners, I'll say, hey, have you tried veterinary non-steroidal anti-inflammatory medications?

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Dr. Justine Lee: They're like, oh no, my dog's on glucosamine, but they haven't actually tried anti-inflammatories.

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Dr. Justine Lee: And so it's so important that you work with your veterinarian to make sure that your dog and cat are in a good BCS, or body condition score.

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Dr. Justine Lee: I always joke for Labrador owners, if someone comes up to you and says, your lab is so skinny, that means they're actually perfect.

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Dr. Justine Lee: Okay, so you should be able to see or feel the ribs really lightly, especially when your dog is running.

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Dr. Justine Lee: And again, you shouldn't be able to feel that big fat pad right over their back or their pelvis.

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Dr. Justine Lee: So, so important just because of, again, that purina study.

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Dr. Justine Lee: So there are a lot of things that we can do preventative medicine-wise and nutrition-wise, and when it comes to helping our pets live longer.

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Dr. Justine Lee: Brennen, I hope you don't mind me bringing this up, but on a total side note, I recently read this book that was directed towards human longevity called Outlive.

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Dr. Justine Lee: And it was how to age gracefully versus just living to old age, right?

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Dr. Justine Lee: We want to make sure that we're mobile, that we're healthy.

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Dr. Justine Lee: And a lot of it is so similar to what we already know.

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Dr. Justine Lee: It's caloric restriction, it's more exercise, it's a lot of things we can do preventative-wise, even when it comes to sleep hygiene, when it comes to our mental health.

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Dr. Justine Lee: So a lot that we can do in terms of our overall lifespan and health span in both human and veterinary medicine.

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Dr. Justine Lee: So with that said, what might be the benefits and disadvantages of longevity drugs?

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Dr. Justine Lee: You mind just telling us a bit more about that and how drugs could play a role in accomplishing longevity?

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Dr. Brennen McKenzie: Happy to.

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Dr. Brennen McKenzie: So one of the problems is that we do know a lot about lifestyle interventions that potentially help extend healthy lifespan.

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Dr. Brennen McKenzie: And yet we have difficulty implementing those, right?

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Dr. Brennen McKenzie: As you've just said, it's difficult to get people to feed their pets to a healthy body condition because food is part of that loving interaction between pet and owner.

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Dr. Brennen McKenzie: And the same is true in humans.

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Dr. Brennen McKenzie: We know that obesity is a health risk, and yet it's been very difficult through simply telling people to eat less and exercise more to accomplish the improvement that we want in that health risk.

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Dr. Brennen McKenzie: And we are now realizing that we need other tools and that medications are not a substitute for living a healthy lifestyle, but they have some advantages.

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Dr. Brennen McKenzie: They are practical.

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Dr. Brennen McKenzie: They often can fit into our life and our routines in a way that is easier than some of the challenging lifestyle interventions like drastic dieting, for example.

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Dr. Brennen McKenzie: And we sometimes forget that some of these lifestyle interventions are actually kind of broad acting things.

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Dr. Brennen McKenzie: If you calorically restrict, you're also protein restricting, you're restricting micronutrients.

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Dr. Brennen McKenzie: You're making a lot of changes in the nutrient intake of a particular individual.

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Dr. Brennen McKenzie: And that's likely to have a lot of effects other than simply reducing body weight.

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Dr. Brennen McKenzie: So even though we think of it as a natural and healthy thing to do, dramatic dieting, for example, has a lot of potential negative health effects.

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Dr. Brennen McKenzie: But if we've understood how caloric restriction extends lifespan and slows aging at a mechanistic level, if we were able to look at the physiology of that process and what the benefits and risks are, drugs potentially offer us an opportunity to target those mechanisms in a more precise and intentional way.

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Dr. Brennen McKenzie: And that potentially has even the chances of having fewer adverse effects than something broad and a blunt tool like a dramatic diet change.

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Dr. Brennen McKenzie: So I think drugs have some advantages in terms of their practicality and their convenience and in terms of being specific and precise in targeting particular mechanisms, rather than just drastically changing the overall physiology of the individual.

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Dr. Justine Lee: Thank you so much.

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Dr. Justine Lee: Such important information.

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Dr. Justine Lee: I can't wait to hear more.

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Dr. Justine Lee: Dr.

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Dr. Justine Lee: Brennen loved the fact that we're even focusing on preventative medicine and the way that we can help our four-legged family members live longer.

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Dr. Justine Lee: We'll be right back with Dr.

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Dr. Justine Lee: Brennen right after these messages.

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Announcer: On Pet Life Radio.

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Dr. Justine Lee: Welcome back to ER Vet on Pet Life Radio.

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Dr. Justine Lee: Again, we're speaking with Dr.

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Dr. Justine Lee: Brennen McKenzie, and we've been talking about lifespan and longevity, and what we can do to help expand both lifespan and health span in our dogs.

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Dr. Justine Lee: I did have a question.

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Dr. Justine Lee: Most of us know, if you've ever had like a small dog versus a Great Dane, like a teacup Tuawa versus a Great Dane, that smaller dogs often live longer than larger dogs.

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Dr. Justine Lee: And it's often hard in the emergency room because I'll see a six or seven-year-old Great Dane come in for life-threatening gastric dilatation volvulus or a stomach bloat.

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Dr. Justine Lee: And unfortunately, that's geriatric for a dog versus at that same age for a teacup Tuawa, I would barely call that one middle age.

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Dr. Justine Lee: So why do smaller dogs live longer?

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Dr. Brennen McKenzie: It's really quite interesting because dogs are an exception to the usual rule in biology.

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Dr. Brennen McKenzie: It's generally well understood that larger animals tend to live longer.

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Dr. Brennen McKenzie: We expect elephants to live longer than mice, and that's a pretty consistent relationship.

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Dr. Brennen McKenzie: In dogs, the opposite is true.

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Dr. Brennen McKenzie: The smaller individuals tend to have shorter life expectancies.

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Dr. Brennen McKenzie: And that's not a natural phenomenon.

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Dr. Brennen McKenzie: That's a consequence of deliberate artificial breeding.

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Dr. Brennen McKenzie: We have selected dogs very intensively and very aggressively, especially over the last couple hundred years, for very specific traits, for appearance, for particular behaviors.

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Dr. Brennen McKenzie: And one of the things that we have bred dogs for is body size.

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Dr. Brennen McKenzie: We have selected these large and giant breed dogs to be large, and we've bred them very intensively to achieve this.

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Dr. Brennen McKenzie: And unfortunately, some of the hormonal and metabolic changes that lead to larger body size have other consequences.

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Dr. Brennen McKenzie: And those consequences include accelerated aging.

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Dr. Brennen McKenzie: So larger dogs live shorter lives, largely because we've made them large through a process that also impacts their aging trajectory.

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Dr. Brennen McKenzie: And then on a practical level, larger dogs can be harder to manage clinically when they get older and they have age-associated diseases.

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Dr. Brennen McKenzie: It's much easier to manage a 15-pound chihuahua that has some arthritis and has difficulty walking than it is 150-pound mastiff.

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Dr. Brennen McKenzie: And so sometimes, unfortunately, we're in the awful position of choosing euthanasia at an earlier age for these larger dogs because they're simply much more difficult to manage effectively.

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Dr. Brennen McKenzie: But most of it has to do with the biology of artificial breeding.

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Dr. Justine Lee: All right, thank you so much.

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Dr. Justine Lee: Now, what are the most promising recent advancements in the field of canine longevity?

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Dr. Justine Lee: Do you mind just telling us a little bit about what you do at Loyal?

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Dr. Brennen McKenzie: So there are a lot of exciting things happening.

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Dr. Brennen McKenzie: Loyal, obviously, is the company that I work for, and I'm very excited about our projects.

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Dr. Brennen McKenzie: There are quite a few other organizations working in the canine aging field as well.

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Dr. Brennen McKenzie: So I think we're really at a pivotal moment in this area where we're going to see a lot of new advancements.

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Dr. Brennen McKenzie: The Dog Aging Project, the Golden Retriever Lifetime Study through the Morris Animal Foundation.

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Dr. Brennen McKenzie: There are lots and lots of efforts going on to do several things.

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Dr. Brennen McKenzie: One is simply to understand aging as well as we can in dogs, how it occurs and what the consequences are.

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Dr. Brennen McKenzie: We know a lot about aging in laboratory rodents, and we know a fair bit in humans, and there are significant similarities across different mammal species, so we can extrapolate to some extent from that knowledge.

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Dr. Brennen McKenzie: But we definitely want to have precise research results in the species we're interested in.

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Dr. Brennen McKenzie: So one of the things we're doing at Loyal with some of our preclinical work and with our upcoming clinical trials is collecting as much data on how dogs age metabolically, what clinical disorders that's associated with, and trying to really understand aging so we know where the targets are for therapies and prevention.

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Dr. Brennen McKenzie: Another thing that we're trying to do is to develop really good reliable tools for measuring the aging process.

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Dr. Brennen McKenzie: When we talk about health span, we have a general idea what we mean, but it would be really great for me as a clinician to have an instrument or a tool that I could use, a biomarker or a survey instrument, to look at a particular dog and say, yeah, you're an eight-year-old golden retriever, but you're in great shape and you're really young physically.

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Dr. Brennen McKenzie: Whereas another eight-year-old golden retriever may have more consequences of aging.

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Dr. Brennen McKenzie: Individuals age differently at different rates.

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Dr. Brennen McKenzie: And we're trying to develop tools to measure things like frailty and health-related quality of life, which are ways of getting at what aging is doing to each individual so we can tailor our prevention and our treatment methods to those individuals where they are.

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Dr. Brennen McKenzie: And then obviously, finally, we're interested in developing more therapeutic tools.

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Dr. Brennen McKenzie: So we are beginning all, we've already actually started to enroll for our first clinical study called the STAY study.

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Dr. Brennen McKenzie: This is to achieve approval through the FDA for the first medication to specifically extend healthy lifespan in dogs.

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Dr. Brennen McKenzie: This is gonna be a four-year study with about 1,000 dogs.

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Dr. Brennen McKenzie: So one of the largest studies, clinical trials in veterinary medicine ever.

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Dr. Brennen McKenzie: And we're really excited about the potential that this could show us that one of our products makes a real meaningful impact on health span and lifespan in dogs.

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Dr. Justine Lee: All right, amazing information.

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Dr. Justine Lee: When it comes to canine longevity and potential drugs, I know that earlier, or a couple months ago, you guys announced a major milestone in bringing dog longevity drugs to market.

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Dr. Justine Lee: And again, this is cutting edge, like most veterinarians don't even know about this.

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Dr. Justine Lee: So the FDA accepted Loyal's reasonable expectation of effectiveness application for a drug that you've been developing for large and giant breed dogs to help them live longer, from my understanding, the name of the drug right now is called LOY-001.

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Dr. Justine Lee: And based on your data or your preliminary data, the FDA believes that this drug is reasonably likely to be effective for large dog lifespan extension in the real world.

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Dr. Justine Lee: So this is totally historic, right?

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Dr. Justine Lee: Because we've never seen anything like this.

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Dr. Justine Lee: So do you mind just telling me a little bit more about, first of all, this drug, what study, I know you just brought up that study, when you expect study results, and how exactly the drug works, if you can disclose that.

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Dr. Brennen McKenzie: Yeah, so Lojwan, which is just our code name for it, because during the FDA approval process, we have some pretty strict rules about what we can and cannot say.

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Dr. Brennen McKenzie: They don't want us to be making any claims for drugs that we haven't proven yet.

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Dr. Brennen McKenzie: Lojwan is a drug that's intended to help mitigate some of the consequences of that intensive breeding of large dogs that I mentioned earlier.

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Dr. Brennen McKenzie: Specifically, it helps to lower levels of growth hormone and something called insulin-like growth factor one in adult dogs.

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Dr. Brennen McKenzie: So after they've reached full growth, we're not trying to make mini Great Danes or anything like that.

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Dr. Brennen McKenzie: And we hope that that will mitigate some of the negative health consequences of that hormonal system.

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Dr. Brennen McKenzie: And the big news was that we've gone through a process called expanded conditional approval.

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Dr. Brennen McKenzie: So the FDA has a very rigorous process for vetting drugs to make sure that they are safe and effective.

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Dr. Brennen McKenzie: And that process includes evidence of safety, evidence that you can manufacture the drug effectively in an appropriate manner, and evidence that the drug works, that it does what you want it to do.

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Dr. Brennen McKenzie: All of those things are necessary for any kind of approval, but for drugs that are treating an untreated problem, a clinically meaningful, important problem that we don't yet have drugs for, and aging is certainly that kind of a problem, you have the opportunity to make the drug available to veterinarians and dog owners earlier in the process through conditional approval.

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Dr. Brennen McKenzie: And that involves the same safety data, the same manufacturing data, all of the other criteria are the same.

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Dr. Brennen McKenzie: But in addition to going through a long-term clinical trial to prove that it's effective, you can market the drug early under conditional approval if you meet the standards of reasonable expectation of effectiveness.

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Dr. Brennen McKenzie: So we have a good body of preclinical data that we've submitted to the agency to say, here's why we think our drug will work, why we think it will extend healthy lifespan in large dogs.

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Dr. Brennen McKenzie: And while we're going to go ahead with the long four year clinical study to demonstrate that definitively, we think this might be worthwhile to make available to veterinarians earlier.

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Dr. Brennen McKenzie: And the FDA has agreed that that evidence is compelling.

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Dr. Brennen McKenzie: And if we go through the rest of the process and meet all of the other milestones, we could potentially bring that drug to market as early as 2026, while we're then conducting a longer term study to verify all the details and make sure that that we're confident in the benefits.

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Dr. Brennen McKenzie: And we have several products in development.

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Dr. Brennen McKenzie: That's for Loy 001.

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Dr. Brennen McKenzie: We also have a product Loy 003, which works in the same way on the same mechanism, but it's intended to be given as a daily tablet prescribed by a veterinarian, whereas 001 is going to be an injectable product that would be used about every three to six months.

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Dr. Brennen McKenzie: We're still working on the best way to make that available to people.

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Dr. Brennen McKenzie: So we have a couple of products in this general category, but the announcement applies to this Loy 001, or the injectable medication, to extend healthy lifespan in large dogs.

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Dr. Justine Lee: Amazing information.

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Dr. Justine Lee: And I'm so glad that I was able to talk to you about it today because, again, dog owners are finding out before a lot of veterinary professionals even know this.

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Dr. Justine Lee: And, you know, I know it oftentimes will take a while to be able to get out and get the drug marketed out there.

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Dr. Justine Lee: But just knowing that we have some hope in helping extend the lives and the health span of our large to giant breeds is so amazing.

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Dr. Justine Lee: I usually have the 50 to 55-pound pit bull mix.

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Dr. Justine Lee: And it's hard when you're trying to counsel people or even like my young child and be like, well, he's only going to live to like 10 to 12, right?

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Dr. Justine Lee: And I often feel like people don't always know what to anticipate for the longevity of their pet.

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Dr. Justine Lee: So anything we can do to help them and help promote a healthy, happy lifespan where they're a good condition, they're happy, they have a good quality of life is so, so important.

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Dr. Justine Lee: Dr.

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Dr. Justine Lee: Brennen, thank you so much.

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Dr. Justine Lee: Any last points you want to leave with us?

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Dr. Brennen McKenzie: I just want people to, you know, hopefully share my enthusiasm and my optimism.

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Dr. Brennen McKenzie: I think we've traditionally thought of aging as just an inevitable part of life, and we wait for bad things to happen and then do the best we can to treat them.

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Dr. Brennen McKenzie: I think that we are at the beginning of a period in which we can take a different approach, where we can prevent a lot of those negative things from happening or delay them and give dogs and their people more happy, healthy time together.

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Dr. Brennen McKenzie: And I'm excited about that potential, and I hope that the rest of the profession will be as well.

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Dr. Justine Lee: Wonderful.

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Dr. Justine Lee: Dr.

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Dr. Justine Lee: Brennen McKenzie, thank you so much.

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Dr. Justine Lee: Love what you do for loyal.

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Dr. Justine Lee: And just wanted to thank you for being on today's show.

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Dr. Brennen McKenzie: Thank you, my pleasure.

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Dr. Justine Lee: Well, that brings us to the end of today's show.

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Dr. Justine Lee: Find me at drjustinely.com, on Facebook or Instagram at drlee, or email me your pet questions at drjustine at petliferadio.com.

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Dr. Justine Lee: With that, we're out of time, and we want to thank our guests, Dr.

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Dr. Justine Lee: Brennen McKenzie and Mark Winter, our producer, for making this show possible.

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Dr. Justine Lee: See you at the next episode.

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