May 22, 2024 • 22 mins
In this episode of ER VET, Dr. Justine Lee, DACVECC, DABT interviews Dr. Brennen McKenzie from Loyal, a biotech company, on what we can potentially do to help our dogs live longer and stay healthier! From keeping our dogs on the “thin” side to minimize osteoarthritis to preventive care to drugs, what can we do to help dogs live longer? Tuen in to learn about a new drug, LOY-001, which they are developing to help large- and giant-breed dogs live longer!
SHOW NOTES: Can We Help Dogs Live Longer with Dr. Brennen McKenzie)
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SHOW NOTES: Can We Help Dogs Live Longer with Dr. Brennen McKenzie)
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:02):
This is pet Life Radio. Let's Talk Pets.
Speaker 2 (00:26):
Welcome to er Vet on pet Life Radio.
Speaker 3 (00:28):
I'm your host, actor Justine Lee, and I'm an emergency
critical care veterinary specialist and a toxicologist.
Speaker 2 (00:34):
Thanks for joining us today.
Speaker 3 (00:35):
We're going to be talking about a cool, amazing new
update about how to make your dog live longer and
what dog owner doesn't want their pets to live longer?
So you want to tune in right after these messages.
Speaker 4 (00:50):
Take a bite out of your competition, advertise your business
with an ad in pet Life Radio podcast and radio shows.
There is no other pet related media that is as
large and reaches more pet parents and pet lovers than
pet Life Radio with over seven million monthly listeners. Pet
Life Radio podcasts are available on all major podcasts platforms,
(01:12):
and our live radio stream goes out to over two
hundred and fifty million subscribers on iHeartRadio, Odyssey, tune In,
and other streaming apps. For more information on how you
can advertise on the number one pet podcast and radio network,
visit Petlife Radio dot com slash advertised today.
Speaker 5 (01:32):
Let's Talk Pets on Petlifradio dot com.
Speaker 2 (01:51):
Welcome back to er Vet on pet Life Radio.
Speaker 3 (01:54):
I'm doctor Justine Lee, and I'm super excited to speak
with doctor Brennan mackenzie, who's a fellow veterinary.
Speaker 2 (02:00):
Brennan, thank you so much for joining us today.
Speaker 6 (02:02):
Thank you my pleasure.
Speaker 3 (02:04):
All right, Jess, 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?
Speaker 6 (02:10):
Absolutely so. I am one foot in two worlds. I
am in clinical practice as a general practitioner. I trained
at the University of Pennsylvania more years ago than I
care to say, and I've been in practice in private
practice for that entire time. But about five years ago
I started working as director of veterinary Medicine for Loyal.
Loyal is a biotechnology startup company based in San Francisco,
(02:31):
and our goal is to develop FDA approved medications to
extend healthy lifespan in dogs. So I'm getting to work
both in the clinical and in the research world.
Speaker 2 (02:41):
Awesome.
Speaker 3 (02:41):
Well, I really appreciate you joining us today, and I
love the stuff that Loyal is starting to do, so
thank you for all that you do. First of all,
now I want to talk to you about the health
span and the lifespan in dogs. First of all, what
exactly is the definition of health span and how is
it related to lifespan and dogs.
Speaker 6 (03:00):
So, lifespan is a word and a concept that everyone's
very familiar with. It's simply the amount of time that
an individual's been alive. 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. So lifespan and health
span are both aspects of the length of time, but
(03:20):
health span refers specifically to health 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. We euthanize them when their quality
of life has reached a point that we feel is unacceptable.
And the ability to extend health span by delaying the
(03:43):
onset of age associated diseases is also the ability to
extend lifespan, because if dogs are healthier and have a
good quality of life, then they will in naturally live longer.
Speaker 3 (03:53):
Sounds like it's important for human medicine too, but that's
a whole another topic. Now, what are some approaches for
extending lifespan and health span and dogs and what role
could drugs play in accomplishing this.
Speaker 6 (04:04):
So there are a number of things that we can
already do to extend the healthy life span of our dogs,
and these are things that as a clinician I talk
to dog owners about all the time, things like preventative
veterinarian care. 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, So simply continuing with good
(04:26):
quality preventative care is an important thing that dog owners
can do to extend the healthy lifespan in their dogs.
We also know that one of the most challenging problems
right now in canine medicine is obesity. We know that
dogs who are overweight have a shorter life expectancy than
dogs who are a healthy weight, so maintaining your dog
a healthy body weight is an important way of extending
(04:47):
lifespan and health span. However, what we're interested in is
giving veterinarians and dog owners more tools to do that,
more tools to prevent the development of age associated disease
and keep dogs happy and healthy longer and we think
that medications can play a role in that. I'll give
you an example. One of the most effective ways to
extend healthy lifespan in a variety of species, which has
(05:08):
been tested in dogs is something called calorie restriction. Purina
did a great study a while back where they paired
up puppies Labrador retriever puppies, and one dog was in
a group that was fed its entire life to a healthy,
normal body condition. The puppy that was matched was fed
to twenty five percent fewer calories than that group. So
all they did for these dogs was some of them
(05:29):
got fed to be a healthy condition and some of
them got fed less. The dogs who were calorie restricted
lived on average a year and a half longer. 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.
So we know that calorie restriction is a way that
you can extend healthy lifespan. The problem is that it's
(05:50):
not a practical, realistic thing to do for our companion dogs.
Food is love. Food is how we show affection and
trying to get people to dramatically restrict how they feed
their dogs likely to interfere with the human animal bond,
and if it's not done carefully with proper supervision, it's
likely to cause malnutrition and actually be harmful. However, what
we've learned from studies like this is that there are
(06:11):
underlying mechanisms of aging that occur that we can manipulate.
So if counter 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.
Speaker 3 (06:30):
I love all that you're bringing up, and thank you
so much for bringing up that Purina study. It's one
of my favorite long term studies and I'm hoping one
day they replicate this in cats.
Speaker 2 (06:39):
But it's probably very similar.
Speaker 4 (06:41):
Right.
Speaker 3 (06:41):
We know there's a huge link between obesity and the
development of osteoarthritis. We know that obesity definitely contributes to
underlying cardiopulmonary problems, part and lung problems, to creating arthritis,
to really affecting the mobility of dogs and cats as
a age, I can't I'll tell you how heartbreaking it
(07:01):
is for me as an emergency of 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 austereithritis that was
worsened by obesity. And oftentimes when I'm talking to pet owners,
I'll say, hey, have you tried veterinary nonstal anti inflammatory medications?
(07:23):
They're like, oh, no, my dog's on glucosamine, but they
haven't actually tried anti inflammatories. 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. 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. Okay, so you
(07:45):
should be able to see or feel the ribs really lightly,
especially when your dog is running. And again you shouldn't
be able to feel that big fat pad right over
their back or their pelvis. So so important just because
of again that purian A study. 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. Brennan, I hope you don't mind me
(08:08):
bringing this up. But on a total side note, I
recently read this book that was directed towards human longevity
called Outlive, and it was how to age gracefully versus
just living to old age. Right, we want to make
sure that we're mobile, that we're healthy, and a lot
of it is so similar to what we already know.
It's caloric restriction, it's more exercise, it's a lot of
(08:31):
things we can do preventative wise, even when it comes
to sleep hygiene, when it comes to our mental health.
Speaker 2 (08:37):
So a lot that we.
Speaker 3 (08:38):
Can do in terms of our overall lifespan and health
span in both human and veterinary medicine. So with that said,
what might be the benefits and disadvantages of longevity drugs?
You might just telling us a bit more about that
and how drugs could play a role in accomplishing longevity.
Speaker 6 (08:56):
Happy to So, one of the problems is that we
do know a lot about lifestyle interventions that potentially help
extend healthy lifespan, and yet we have difficulty implementing those
right 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,
(09:17):
and the same is true in humans. 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. 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. They
(09:38):
are practical, 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,
And we sometimes forget that some of these lifestyle interventions
are actually kind of broad acting things. If you calorically restrict,
you're also protein restricting, restricting micronutrients. You're making a lot
(10:02):
of changes in the nutrient intake of a particular individual,
and that's likely to have a lot of effects other
than simply reducing body weight. 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. But if we've understood how colored restriction extends
lifespan and slows aging at a mechanistic level, if we're
(10:23):
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, and that potentially has even the chances
of having fewer adverse effects than something broad and a
blunt tool like a dramatic diet change. So I think
(10:45):
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.
Speaker 3 (10:56):
Of the individual. Thank you so much, such important information.
I can't wait to hear more, Doctor Brennon. Love the
fact that we're even focusing on prevented medicine in the
way that we can help our four legged family members
live longer. We'll be right back with doctor Brennon right
after these.
Speaker 7 (11:11):
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Speaker 5 (11:36):
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Speaker 8 (11:39):
Radio, Headline Radio, pet live Radio dot Com.
Speaker 2 (11:58):
Welcome back to er Vet on pet Life Radio again.
Speaker 3 (12:01):
We're speaking with doctor Brennan 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.
I did have a question most of us know, if
you've ever had, like a small dog versus a Great Dane,
like a teacup chiuaha versus a Great Dane, that smaller
(12:21):
dogs often live longer than larger dogs. And it's often
hard in the emergency room because I'll see six or
seven year old Great Dane come in for life threatening
gashic diletation, bovulus or a stomach bloat, and unfortunately that's
geriatric for a dog versus at that same age for
teacup chiuaha, I would barely call that in middle age.
(12:44):
So why do smaller dogs live longer?
Speaker 6 (12:46):
It's really quite interesting because dogs are an exception to
the usual rule in biology. It's generally well understood that
larger animals tend to live longer. We expect elephants to
live longer than mice, and that's a pretty consistent relationship.
In dogs, the opposite is true. The smaller individuals tend
to have shorter life expectancies, and that's not a natural phenomenon.
That's a consequence of deliberate artificial breeding. We have selected
(13:10):
dogs very intensively and very aggressively, especially over the last
couple hundred years, for very specific traits, for appearance, for
particular behaviors, and one of the things that we have
bred dogs for is body size. We have selected these
large and giant free dogs to be large, and we've
bred them very intensively to achieve this. And unfortunately, some
of the hormonal and metabolic changes that lead to larger
(13:33):
body size have other consequences, and those consequences include accelerated aging.
So larger dogs live shorter lives, largely because we've made
them large through a process that also impacts their aging trajectory.
And then, on a practical level, larger dogs can be
harder to manage clinically when they get older and they
have age associated diseases. It's much easier to manage a
(13:55):
fifteen pound Chuala that has some arthritis and has difficulty
walking than it is one hundred and fifty pound mastiff,
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. But
most of it has to do with the biology of
artificial breeding.
Speaker 3 (14:15):
All right, thank you so much. Now, what are the
most promising recent advancements in the field of canine longevity?
Do you mind just telling us a little bit about
what you do at Loyal.
Speaker 6 (14:25):
So there are a lot of exciting things happening. Loyle
obviously is the company that I work for, and I'm
very excited about our projects. There are quite a few
other organizations working in the canine aging field as well,
so I think we're really at a pivotal moment in
this area where we're going to see a lot of
new advancements. The Dog Aging Project, the Golden Retriever Lifetime
Study through the Morris Animal Foundation, there are lots and
(14:45):
lots of efforts going on to do several things. One
is simply to understand aging as well as we can
and dogs, how it occurs and what the consequences are.
We know a lot about aging and 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, but we definitely want
(15:05):
to have precise research results in the species we're interested in.
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. Another thing that we're trying to do
(15:27):
is develop really good, reliable tools for measuring the aging process.
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, whereas another eight
(15:50):
year old Golden retriever may have more consequences of aging.
Individuals age differently at different rates, and we're trying to
develop tools to measure things like frailty and health related
quality of life, which are ways of getting it what
aging is doing to each individual, so we can tailor
our prevention in our treatment methods to those individuals where
they are. And then obviously, finally we're interested in developing
(16:12):
more therapeutic tools. So we are beginning. All we've already
actually started to enroll for our first clinical study called
the Stay Study. This is to achieve approval through the
FDA for the first medication to specifically extend healthy lifespan
in dogs. This is going to be a four year
study with about one thousand dogs, so one of the
largest studies, clinical trials and veterinary medicine ever, and we're
(16:34):
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.
Speaker 3 (16:42):
All right, amazing information when it comes to canon longevity
and potential drugs. I know that earlier, over a couple
months ago, you guys announced a major milestone and bringing
dog longevity drugs to market. And again this is cutting edge,
like most veterinarians don't even know about that. So the
FDA accepted loyals reasonable Expectation of effectiveness application for a
(17:07):
drug that you've been developing for large and giant breed
dogs to help them live long. From my understanding, the
name of the drug right now is called loy dashoer
zer A one, 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. So this is totally historic, right because
(17:29):
we've never seen anything like this. 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.
Speaker 6 (17:44):
Yeah, So loi wan, which is just our code name
for it, because during the FDA approval process, you know,
we have some pretty strict rules about what we can
and cannot say. They don't want us to be making
any claims for drugs that we haven't proven yet. Loy
One is a drug that's intended to help mitigate some
of the consequences of that intensive breeding of large dogs
that I mentioned earlier. Specifically, it helps to lower levels
(18:06):
of growth hormone and something called insulin light growth factor
one in adult dogs, so after they've reached full growth,
we're not trying to make mini great Danes or anything
like that, and we hope that that will mitigate some
of the negative health consequences of that hormonal system. And
the big news was that we've gone through a process
called Conditional expanded Conditional approval, So the FDA has a
(18:29):
very rigorous process for vetting drugs to make sure that
they are safe and effective, 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. All
of those things are necessary for any kind of approval,
but for drugs that are treating an untreated problem, a
(18:50):
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,
and that involves the same safety data, the same manufacturing data,
all of the other criteria are the same. But in
addition to going through a long term clinical trial to
(19:12):
prove that it's effective, you can market the drug early
under conditional approval if you meet the standards of reasonable
expectation of effectiveness. 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, and
while we're going to go ahead with the long four
year clinical study to demonstrate that definitively, we think this
(19:35):
might be worthwhile to make available to veterinarians earlier, and
the FDA has agreed that that evidence is compelling, 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 twenty twenty six,
while we're then conducting a longer term study to verify
all the details and make sure that we're confident in
the benefits, and we have several products in development. That's
(19:58):
for Loyo one. We also have product Loyo three, which
works in the same way on the same mechanism, but
it's intended to be given as a daily tablet prescribed
via a veterinarian, whereas one is going to be an
injectable product that would be used about every three to
six months. We're still working on the best way to
make that available to people. So we have a couple
of products in this general category, but the announcement applies
(20:20):
to this Loyo one or the injectable medication to extend
healthy lifespan in large dogs.
Speaker 3 (20:25):
Amazing information 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, and you know, I know it oftentimes
will take a while to be able to get out
and get the drug marketed out there, But just knowing
that we have some hope in helping extend the lives
and the health span of our large to.
Speaker 2 (20:47):
Giant breeds is so amazing.
Speaker 3 (20:49):
I usually have the fifty to fifty five pound pit
bull mix, 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 ten to twelve, right,
I know if you feel like people don't always know
what to anticipate for the longevity of their pets. So
anything we can do to help them and help promote
a healthy, happy lifespan where they're a good condition, they're happy,
(21:13):
there have a good quality of life is.
Speaker 2 (21:15):
So so important, Doctor Brennan, thank you so much. Any
last point you want to leave with us, I.
Speaker 6 (21:20):
Just want people to, you know, hopefully share my enthusiasm
and my optimism. 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. 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
(21:41):
give dogs and their people more happy, healthy time together.
And I'm excited about that potential, and I hope that
the rest of the profession will be as well.
Speaker 3 (21:49):
Wonderful, Doctor Brenna Mackenzie, thank you so much love what
you do for loyal and just wanted to thank you
for being on today's show.
Speaker 6 (21:55):
Thank you my pleasure.
Speaker 3 (21:56):
Well that brings us to the end of today's show,
Doctor Justinelee dot com, on Facebook or Instagram at doctor
Lee or email me your pet questions at doctor Justine
at Petlife radio dot com.
Speaker 2 (22:07):
With that, we're out of time and we want to thank.
Speaker 3 (22:09):
Our guests, doctor Brennan Mackenzie and Mark Winter, our producer,
for making this show possible.
Speaker 2 (22:14):
See you at the next episode.
Speaker 5 (22:16):
Let's Talk Pets every week on demand only on Petlife
Radio dot com.
This is pet Life Radio. Let's Talk Pets.
Speaker 2 (00:26):
Welcome to er Vet on pet Life Radio.
Speaker 3 (00:28):
I'm your host, actor Justine Lee, and I'm an emergency
critical care veterinary specialist and a toxicologist.
Speaker 2 (00:34):
Thanks for joining us today.
Speaker 3 (00:35):
We're going to be talking about a cool, amazing new
update about how to make your dog live longer and
what dog owner doesn't want their pets to live longer?
So you want to tune in right after these messages.
Speaker 4 (00:50):
Take a bite out of your competition, advertise your business
with an ad in pet Life Radio podcast and radio shows.
There is no other pet related media that is as
large and reaches more pet parents and pet lovers than
pet Life Radio with over seven million monthly listeners. Pet
Life Radio podcasts are available on all major podcasts platforms,
(01:12):
and our live radio stream goes out to over two
hundred and fifty million subscribers on iHeartRadio, Odyssey, tune In,
and other streaming apps. For more information on how you
can advertise on the number one pet podcast and radio network,
visit Petlife Radio dot com slash advertised today.
Speaker 5 (01:32):
Let's Talk Pets on Petlifradio dot com.
Speaker 2 (01:51):
Welcome back to er Vet on pet Life Radio.
Speaker 3 (01:54):
I'm doctor Justine Lee, and I'm super excited to speak
with doctor Brennan mackenzie, who's a fellow veterinary.
Speaker 2 (02:00):
Brennan, thank you so much for joining us today.
Speaker 6 (02:02):
Thank you my pleasure.
Speaker 3 (02:04):
All right, Jess, 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?
Speaker 6 (02:10):
Absolutely so. I am one foot in two worlds. I
am in clinical practice as a general practitioner. I trained
at the University of Pennsylvania more years ago than I
care to say, and I've been in practice in private
practice for that entire time. But about five years ago
I started working as director of veterinary Medicine for Loyal.
Loyal is a biotechnology startup company based in San Francisco,
(02:31):
and our goal is to develop FDA approved medications to
extend healthy lifespan in dogs. So I'm getting to work
both in the clinical and in the research world.
Speaker 2 (02:41):
Awesome.
Speaker 3 (02:41):
Well, I really appreciate you joining us today, and I
love the stuff that Loyal is starting to do, so
thank you for all that you do. First of all,
now I want to talk to you about the health
span and the lifespan in dogs. First of all, what
exactly is the definition of health span and how is
it related to lifespan and dogs.
Speaker 6 (03:00):
So, lifespan is a word and a concept that everyone's
very familiar with. It's simply the amount of time that
an individual's been alive. 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. So lifespan and health
span are both aspects of the length of time, but
(03:20):
health span refers specifically to health 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. We euthanize them when their quality
of life has reached a point that we feel is unacceptable.
And the ability to extend health span by delaying the
(03:43):
onset of age associated diseases is also the ability to
extend lifespan, because if dogs are healthier and have a
good quality of life, then they will in naturally live longer.
Speaker 3 (03:53):
Sounds like it's important for human medicine too, but that's
a whole another topic. Now, what are some approaches for
extending lifespan and health span and dogs and what role
could drugs play in accomplishing this.
Speaker 6 (04:04):
So there are a number of things that we can
already do to extend the healthy life span of our dogs,
and these are things that as a clinician I talk
to dog owners about all the time, things like preventative
veterinarian care. 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, So simply continuing with good
(04:26):
quality preventative care is an important thing that dog owners
can do to extend the healthy lifespan in their dogs.
We also know that one of the most challenging problems
right now in canine medicine is obesity. We know that
dogs who are overweight have a shorter life expectancy than
dogs who are a healthy weight, so maintaining your dog
a healthy body weight is an important way of extending
(04:47):
lifespan and health span. However, what we're interested in is
giving veterinarians and dog owners more tools to do that,
more tools to prevent the development of age associated disease
and keep dogs happy and healthy longer and we think
that medications can play a role in that. I'll give
you an example. One of the most effective ways to
extend healthy lifespan in a variety of species, which has
(05:08):
been tested in dogs is something called calorie restriction. Purina
did a great study a while back where they paired
up puppies Labrador retriever puppies, and one dog was in
a group that was fed its entire life to a healthy,
normal body condition. The puppy that was matched was fed
to twenty five percent fewer calories than that group. So
all they did for these dogs was some of them
(05:29):
got fed to be a healthy condition and some of
them got fed less. The dogs who were calorie restricted
lived on average a year and a half longer. 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.
So we know that calorie restriction is a way that
you can extend healthy lifespan. The problem is that it's
(05:50):
not a practical, realistic thing to do for our companion dogs.
Food is love. Food is how we show affection and
trying to get people to dramatically restrict how they feed
their dogs likely to interfere with the human animal bond,
and if it's not done carefully with proper supervision, it's
likely to cause malnutrition and actually be harmful. However, what
we've learned from studies like this is that there are
(06:11):
underlying mechanisms of aging that occur that we can manipulate.
So if counter 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.
Speaker 3 (06:30):
I love all that you're bringing up, and thank you
so much for bringing up that Purina study. It's one
of my favorite long term studies and I'm hoping one
day they replicate this in cats.
Speaker 2 (06:39):
But it's probably very similar.
Speaker 4 (06:41):
Right.
Speaker 3 (06:41):
We know there's a huge link between obesity and the
development of osteoarthritis. We know that obesity definitely contributes to
underlying cardiopulmonary problems, part and lung problems, to creating arthritis,
to really affecting the mobility of dogs and cats as
a age, I can't I'll tell you how heartbreaking it
(07:01):
is for me as an emergency of 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 austereithritis that was
worsened by obesity. And oftentimes when I'm talking to pet owners,
I'll say, hey, have you tried veterinary nonstal anti inflammatory medications?
(07:23):
They're like, oh, no, my dog's on glucosamine, but they
haven't actually tried anti inflammatories. 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. 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. Okay, so you
(07:45):
should be able to see or feel the ribs really lightly,
especially when your dog is running. And again you shouldn't
be able to feel that big fat pad right over
their back or their pelvis. So so important just because
of again that purian A study. 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. Brennan, I hope you don't mind me
(08:08):
bringing this up. But on a total side note, I
recently read this book that was directed towards human longevity
called Outlive, and it was how to age gracefully versus
just living to old age. Right, we want to make
sure that we're mobile, that we're healthy, and a lot
of it is so similar to what we already know.
It's caloric restriction, it's more exercise, it's a lot of
(08:31):
things we can do preventative wise, even when it comes
to sleep hygiene, when it comes to our mental health.
Speaker 2 (08:37):
So a lot that we.
Speaker 3 (08:38):
Can do in terms of our overall lifespan and health
span in both human and veterinary medicine. So with that said,
what might be the benefits and disadvantages of longevity drugs?
You might just telling us a bit more about that
and how drugs could play a role in accomplishing longevity.
Speaker 6 (08:56):
Happy to So, one of the problems is that we
do know a lot about lifestyle interventions that potentially help
extend healthy lifespan, and yet we have difficulty implementing those
right 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,
(09:17):
and the same is true in humans. 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. 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. They
(09:38):
are practical, 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,
And we sometimes forget that some of these lifestyle interventions
are actually kind of broad acting things. If you calorically restrict,
you're also protein restricting, restricting micronutrients. You're making a lot
(10:02):
of changes in the nutrient intake of a particular individual,
and that's likely to have a lot of effects other
than simply reducing body weight. 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. But if we've understood how colored restriction extends
lifespan and slows aging at a mechanistic level, if we're
(10:23):
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, and that potentially has even the chances
of having fewer adverse effects than something broad and a
blunt tool like a dramatic diet change. So I think
(10:45):
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.
Speaker 3 (10:56):
Of the individual. Thank you so much, such important information.
I can't wait to hear more, Doctor Brennon. Love the
fact that we're even focusing on prevented medicine in the
way that we can help our four legged family members
live longer. We'll be right back with doctor Brennon right
after these.
Speaker 7 (11:11):
Messages, begging to hear more of your favorite show. Full
episodes of all our shows are available on demand. Go
to petlife Radio dot com to vet our entire lineup
of powsome pet podcasts. Also dig us up in iHeartRadio
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Speaker 5 (11:36):
Let's talk past it, Let's done petto Life.
Speaker 8 (11:39):
Radio, Headline Radio, pet live Radio dot Com.
Speaker 2 (11:58):
Welcome back to er Vet on pet Life Radio again.
Speaker 3 (12:01):
We're speaking with doctor Brennan 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.
I did have a question most of us know, if
you've ever had, like a small dog versus a Great Dane,
like a teacup chiuaha versus a Great Dane, that smaller
(12:21):
dogs often live longer than larger dogs. And it's often
hard in the emergency room because I'll see six or
seven year old Great Dane come in for life threatening
gashic diletation, bovulus or a stomach bloat, and unfortunately that's
geriatric for a dog versus at that same age for
teacup chiuaha, I would barely call that in middle age.
(12:44):
So why do smaller dogs live longer?
Speaker 6 (12:46):
It's really quite interesting because dogs are an exception to
the usual rule in biology. It's generally well understood that
larger animals tend to live longer. We expect elephants to
live longer than mice, and that's a pretty consistent relationship.
In dogs, the opposite is true. The smaller individuals tend
to have shorter life expectancies, and that's not a natural phenomenon.
That's a consequence of deliberate artificial breeding. We have selected
(13:10):
dogs very intensively and very aggressively, especially over the last
couple hundred years, for very specific traits, for appearance, for
particular behaviors, and one of the things that we have
bred dogs for is body size. We have selected these
large and giant free dogs to be large, and we've
bred them very intensively to achieve this. And unfortunately, some
of the hormonal and metabolic changes that lead to larger
(13:33):
body size have other consequences, and those consequences include accelerated aging.
So larger dogs live shorter lives, largely because we've made
them large through a process that also impacts their aging trajectory.
And then, on a practical level, larger dogs can be
harder to manage clinically when they get older and they
have age associated diseases. It's much easier to manage a
(13:55):
fifteen pound Chuala that has some arthritis and has difficulty
walking than it is one hundred and fifty pound mastiff,
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. But
most of it has to do with the biology of
artificial breeding.
Speaker 3 (14:15):
All right, thank you so much. Now, what are the
most promising recent advancements in the field of canine longevity?
Do you mind just telling us a little bit about
what you do at Loyal.
Speaker 6 (14:25):
So there are a lot of exciting things happening. Loyle
obviously is the company that I work for, and I'm
very excited about our projects. There are quite a few
other organizations working in the canine aging field as well,
so I think we're really at a pivotal moment in
this area where we're going to see a lot of
new advancements. The Dog Aging Project, the Golden Retriever Lifetime
Study through the Morris Animal Foundation, there are lots and
(14:45):
lots of efforts going on to do several things. One
is simply to understand aging as well as we can
and dogs, how it occurs and what the consequences are.
We know a lot about aging and 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, but we definitely want
(15:05):
to have precise research results in the species we're interested in.
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. Another thing that we're trying to do
(15:27):
is develop really good, reliable tools for measuring the aging process.
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, whereas another eight
(15:50):
year old Golden retriever may have more consequences of aging.
Individuals age differently at different rates, and we're trying to
develop tools to measure things like frailty and health related
quality of life, which are ways of getting it what
aging is doing to each individual, so we can tailor
our prevention in our treatment methods to those individuals where
they are. And then obviously, finally we're interested in developing
(16:12):
more therapeutic tools. So we are beginning. All we've already
actually started to enroll for our first clinical study called
the Stay Study. This is to achieve approval through the
FDA for the first medication to specifically extend healthy lifespan
in dogs. This is going to be a four year
study with about one thousand dogs, so one of the
largest studies, clinical trials and veterinary medicine ever, and we're
(16:34):
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.
Speaker 3 (16:42):
All right, amazing information when it comes to canon longevity
and potential drugs. I know that earlier, over a couple
months ago, you guys announced a major milestone and bringing
dog longevity drugs to market. And again this is cutting edge,
like most veterinarians don't even know about that. So the
FDA accepted loyals reasonable Expectation of effectiveness application for a
(17:07):
drug that you've been developing for large and giant breed
dogs to help them live long. From my understanding, the
name of the drug right now is called loy dashoer
zer A one, 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. So this is totally historic, right because
(17:29):
we've never seen anything like this. 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.
Speaker 6 (17:44):
Yeah, So loi wan, which is just our code name
for it, because during the FDA approval process, you know,
we have some pretty strict rules about what we can
and cannot say. They don't want us to be making
any claims for drugs that we haven't proven yet. Loy
One is a drug that's intended to help mitigate some
of the consequences of that intensive breeding of large dogs
that I mentioned earlier. Specifically, it helps to lower levels
(18:06):
of growth hormone and something called insulin light growth factor
one in adult dogs, so after they've reached full growth,
we're not trying to make mini great Danes or anything
like that, and we hope that that will mitigate some
of the negative health consequences of that hormonal system. And
the big news was that we've gone through a process
called Conditional expanded Conditional approval, So the FDA has a
(18:29):
very rigorous process for vetting drugs to make sure that
they are safe and effective, 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. All
of those things are necessary for any kind of approval,
but for drugs that are treating an untreated problem, a
(18:50):
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,
and that involves the same safety data, the same manufacturing data,
all of the other criteria are the same. But in
addition to going through a long term clinical trial to
(19:12):
prove that it's effective, you can market the drug early
under conditional approval if you meet the standards of reasonable
expectation of effectiveness. 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, and
while we're going to go ahead with the long four
year clinical study to demonstrate that definitively, we think this
(19:35):
might be worthwhile to make available to veterinarians earlier, and
the FDA has agreed that that evidence is compelling, 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 twenty twenty six,
while we're then conducting a longer term study to verify
all the details and make sure that we're confident in
the benefits, and we have several products in development. That's
(19:58):
for Loyo one. We also have product Loyo three, which
works in the same way on the same mechanism, but
it's intended to be given as a daily tablet prescribed
via a veterinarian, whereas one is going to be an
injectable product that would be used about every three to
six months. We're still working on the best way to
make that available to people. So we have a couple
of products in this general category, but the announcement applies
(20:20):
to this Loyo one or the injectable medication to extend
healthy lifespan in large dogs.
Speaker 3 (20:25):
Amazing information 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, and you know, I know it oftentimes
will take a while to be able to get out
and get the drug marketed out there, But just knowing
that we have some hope in helping extend the lives
and the health span of our large to.
Speaker 2 (20:47):
Giant breeds is so amazing.
Speaker 3 (20:49):
I usually have the fifty to fifty five pound pit
bull mix, 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 ten to twelve, right,
I know if you feel like people don't always know
what to anticipate for the longevity of their pets. So
anything we can do to help them and help promote
a healthy, happy lifespan where they're a good condition, they're happy,
(21:13):
there have a good quality of life is.
Speaker 2 (21:15):
So so important, Doctor Brennan, thank you so much. Any
last point you want to leave with us, I.
Speaker 6 (21:20):
Just want people to, you know, hopefully share my enthusiasm
and my optimism. 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. 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
(21:41):
give dogs and their people more happy, healthy time together.
And I'm excited about that potential, and I hope that
the rest of the profession will be as well.
Speaker 3 (21:49):
Wonderful, Doctor Brenna Mackenzie, thank you so much love what
you do for loyal and just wanted to thank you
for being on today's show.
Speaker 6 (21:55):
Thank you my pleasure.
Speaker 3 (21:56):
Well that brings us to the end of today's show,
Doctor Justinelee dot com, on Facebook or Instagram at doctor
Lee or email me your pet questions at doctor Justine
at Petlife radio dot com.
Speaker 2 (22:07):
With that, we're out of time and we want to thank.
Speaker 3 (22:09):
Our guests, doctor Brennan Mackenzie and Mark Winter, our producer,
for making this show possible.
Speaker 2 (22:14):
See you at the next episode.
Speaker 5 (22:16):
Let's Talk Pets every week on demand only on Petlife
Radio dot com.
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