ºÙºÙÊÓƵ

 

Photo of Myrtle, a brown, tan, and white English bulldog, as a puppy wearing a rainbow outfit
Myrtle, an English bulldog, was part of a clinical trial at ºÙºÙÊÓƵ School of Veterinary Medicine using stem cells and surgery to treat her spina bifida. Myrtle was adopted by Katie Teykaerts after the trial. (Credit: Katie Teykaerts)

 

Spina bifida is the most common cause of lifelong childhood paralysis in the United States; approximately four children are born with this devastating defect every day. Standard care usually involves surgery, but it still leaves more than half of children unable to walk. Dogs are also sometimes born with spina bifida and most are euthanized at birth. But a combination of surgery and stem cell treatment may offer hope to both children and dogs. In the first of two episodes of Unfold, we examine the first clinical trial to treat bulldogs with spina bifida and the world’s first human clinical trial using stem cells before birth to treat the most serious form of the disease.

In this episode:

, professor emeritus, neurosurgeon at ºÙºÙÊÓƵ School of Veterinary Medicine 

, biomedical engineer with ºÙºÙÊÓƵ School of Medicine

, pediatric surgeon and chair of surgery at ºÙºÙÊÓƵ Health

Katie Teykaerts, owner of Myrtle, a dog with spina bifida enrolled in a clinical trial

Transcriptions may contain errors.

 

Amy Quinton
Meet Myrtle, a tricolor English bulldog. She's huffing and puffing while taking a walk in the park with her human, Katie Teykaerts.

 

Katie Teykaerts
She's not a quiet dog at all.

 

Amy Quinton
Bulldogs have flat little faces, which makes breathing a bit more difficult and walks well, not terribly long. But for Katie, that doesn't matter. For her, it was love at first sight.

 

Katie Teykaerts
So, she's really cute. She just, especially with the tricolor like her eyebrows are so expressive, and then she has her little white waterfall above her nose. And she's, like that, and she'll look at you and like her teeth are uneven in the front, so she'll get her lips caught on her little snaggle teeth, and so she was just impossible not to fall in love with.

 

Amy Quinton
For the most part, Myrtle is like any other English bulldog, except for the cow print diapers.

 

Katie Teykaerts
She's a Pampers size 7 and she's pretty much stayed at that weight. And we've been really lucky about that. She's a good weight for avoiding some of the hip problems that bulldogs just in general have.

 

Amy Quinton
Bulldogs are prone to health problems, and Myrtle has one of the toughest. She was born with spina bifida. It left her incontinent and unable to use her hind quarters. But now she's able to walk thanks to a clinical trial examining a new surgery and stem cell treatment for spina bifida that translates to humans as well. In this episode of Unfold, we'll look at how animals are providing hope for a spinal bifida cure.

 

Amy Quinton
Coming to you from ºÙºÙÊÓƵ

 

Marianne Russ Sharp
and ºÙºÙÊÓƵ Health

 

Amy Quinton
This is Unfold, a podcast that breaks down complicated problems and unfolds curiosity-driven research. I'm Amy Quinton.

 

Marianne Russ Sharp
and I'm Marianne Russ Sharp.

 

Amy Quinton
Marianne is with ºÙºÙÊÓƵ Health and our new co-host this season.

 

Marianne Russ Sharp
I'm here because this season's episodes of Unfold are focused on health.

 

Marianne Russ Sharp
Spina bifida is the most common cause of lifelong childhood paralysis in the United States. About four children are born with it every day. It occurs when a developing baby's spinal cord doesn't form properly in the womb. Part of the spinal cord and surrounding tissues are exposed through a gap in the back.

 

Amy Quinton
And dogs also get spina bifida. You just heard about Myrtle an English bulldog born with the abnormality. She's lucky because most puppies born with spina bifida are euthanized.

 

Marianne Russ Sharp
How did Myrtle escape that fate?

 

Amy Quinton
Well, it started with Dr. Diana Farmer.

 

Marianne Russ Sharp
She's the chair of the surgery department at ºÙºÙÊÓƵ Health and a pediatric surgeon. You might be wondering, what does pediatric surgery have to do with spina bifida in bulldogs?

 

Amy Quinton
Farmer has been working on a cure for spina bifida for 25 years, although her interest in finding a cure began when she was a child. Her mother taught at a school for children with disabilities.

 

Diana Farmer
And I remember thinking how unfair it was for a child to be born paralyzed. And for families who didn't really realize the extent of the disability that their child might have until their child grew up, because in this disease, spina bifida, the real manifestations don't show up until later in life.

 

Marianne Russ Sharp
That's when parents realize their child may not be able to walk.

 

Amy Quinton
Spina bifida comes with other serious problems too.

 

Diana Farmer
The possibility of a child having lifelong paralysis, lifelong bowel and bladder deformities. There are some other fluid on the brain, hydrocephalus, is something that's associated with spina bifida.

 

Marianne Russ Sharp
If left untreated, hydrocephalus can damage brain tissues.

 

Amy Quinton
But about 20 years ago, Farmer was part of a team that conducted the first clinical trial showing prenatal surgery to close the gap in the spine significantly reduced the possibility of a child developing fluid in the brain.

 

Diana Farmer
That was a huge shift and an amazingly positive outcome. It almost eliminated entirely that problem for future children.

 

Marianne Russ Sharp
And more amazingly, Amy it also improved the possibility a child could walk, but it wasn't a cure, because more than half of children who have the surgery are still unable to walk.

 

Amy Quinton
But Farmer saw that is a glass half full.

 

Diana Farmer
Just the fact that you could make any improvement in my mind opened the door to being able to make more improvement.

 

Marianne Russ Sharp
Farmer turned to one of the newer technologies at the time, stem cell therapy, but they had to find stem cells that could reverse the neurological damage and that was no easy task.

 

Amy Quinton
So, Farmer worked with biomedical stem cell engineer Dr. Aijun Wang at ºÙºÙÊÓƵ Health. Wang says that once someone is paralyzed, it's very difficult to regain function because you have to get neurons, or nerve cells, to regrow or reconnect.

 

Aijun Wang
We know that neurons in spina bifida, actually, they are formed initially but they are killed by the environment later on, because they are, the spinal cord is exposed.

 

Marianne Russ Sharp
So, they had to figure out how to develop stem cells that would protect those neurons, so they wouldn't die.

 

Amy Quinton
Right. So, the answer? Placental stem cells.

 

Diana Farmer
We discovered they had, appeared to have, amazing characteristics, special, well, I like to call it the magic stem cell juice. But it's much more complicated than that.

 

Marianne Russ Sharp
I love it. Magic stem cell juice. It's perfect.

 

Amy Quinton
Wang says the stem cells are able to secrete lots of important growth factors.

 

Aijun Wang
The juice, the magic juice can protect neurons from death, from being apoptotic from being killed by other cells. It's a very sort of a protection shield to these neurons.

 

Marianne Russ Sharp
And these stem cells and their magic juice would be held in place by a special engineered patch, a lot like a scaffold. It's placed directly on the spinal cord during surgery.

 

Amy Quinton
But first, they wanted to try the treatment on a sheep that was pregnant with twins with spina bifida, one of the twins received the patch with stem cells, the other received the patch without the stem cells.

 

Marianne Russ Sharp
And guess what happened.

 

Diana Farmer
And it was almost too good to be true. The lamb with the cells was able to walk because lambs walk right at birth, and the other lamb could not even stand up on its hind legs. And we just, it was too good to be true. We didn't believe it.

 

Aijun Wang
That was a big moment. I still remember that day when our lab manager came to me and Dr. Farmer actually saying that the lamb was able to walk. I was like, "You gotta be kidding me."

 

Amy Quinton
They tested the stem cells again. Still, the results were the same. The lambs could walk. But Farmer says it was important to have a model more like a human and one in which spina bifida occurs naturally.

 

Marianne Russ Sharp
I'm gonna go out on a limb here and guess bulldogs.

 

Amy Quinton
Bulldogs.

 

Diana Farmer
It would do two things, it would A, help these puppies that are otherwise euthanized and B, it would help us have more confidence that the principal was correct that the placental-derived stem cells engineered in this method would work.

 

Marianne Russ Sharp
Amy, you visited the ºÙºÙÊÓƵ School of Veterinary Medicine to learn more about spina bifida in bulldogs.

 

Amy Quinton
Right and to learn more about whether the stem cell treatment could offer hope for them too.

 

Marianne Russ Sharp
Okay, so where does this story start?

 

Amy Quinton
With Professor and veterinary neurosurgeon Dr. Beverly Sturges.

 

Beverly Sturges
I might put her up on the table.

 

Amy Quinton
Inside the Veterinary Medical Teaching Hospital, Sturges and her students have a 16-week-old English bulldog on an exam table.

 

Beverly Sturges
Okay, so aside from the cough, do we know anything else about she's been doing?

 

Student
No other problems to report.

 

Amy Quinton
Sturges says bulldogs are the sweetest and as if on cue, the bulldog, named Pippo, rolls over for a belly rub.

 

Beverly Sturges
Should we give a belly rub here. Should we give a belly rub here.

 

Amy Quinton
Pippo thoroughly enjoys it. Pippo does not have spina bifida. But Sturges says the breed is a perfect model to try the new surgery and stem cell treatment.

 

Beverly Sturges
With some regularity, we were seeing spina bifida in bulldogs. It actually happens in bulldogs of all kinds, but the English bulldog seemed to have a spina bifida that was pretty much limited to one area of the spine.

 

Amy Quinton
When an owner chooses not to euthanize a bulldog with spina bifida, there is a surgery that can repair the spine. It's not done in utero because diagnosis doesn't happen until after the dog is born. But the surgery is also rarely performed. And, as is the case with humans, improvement can be unpredictable.

 

Beverly Sturges
We can correct the problem of the spinal cord and nerve roots coming out of their normal place in the spine. But fixing the function, the way those cells within the spinal cord relate to each other and communicate with each other, that is the part we really haven't made any headway.

 

Amy Quinton
Farmer and Wang approached Sturges and asked her if she was willing to try the surgery and their stem cell treatment on bulldogs. Sturges jumped at the chance.

 

Beverly Sturges
I'm an animal lover and a dog lover. For me, it's enough to get a treatment for the dog, to fix the dog, but then to be able to translate this into people and help people, to help little babies with this condition, I mean there's just nothing better.

 

Amy Quinton
Then, in 2017, the perfect candidates for the treatment were born.

 

Beverly Sturges
We had a couple little pups named Darla and Spanky. I think Dr. Wang identified them early on and said, you know, do you think we can try this? And we said, Yeah, let's let's try this. Let's see if we can implant the stem cells. At the time that we do surgery and follow and see how these little dogs do. And everything went amazingly smoothly.

 

Amy Quinton
They did the surgery when the bulldog siblings were just 10-weeks-old. And at their two-month follow-up appointment that year, Darla and Spanky were running around and playing.

 

Beverly Sturges
You're getting so big. He's grown more than she has, hasn't he?

 

Amy Quinton
While the surgery and stem cell treatment gave Darla and Spanky the ability to walk again. It also left more questions for veterinarians. Would the approach work on all bulldogs consistently? And would it be better than just surgery alone? And could it relieve other complications from the condition?

 

Marianne Russ Sharp
Amy, how are Darla and Spanky doing now?

 

Amy Quinton
I'm told they're doing great. Sturges says they were adopted by wonderful people in New Mexico who live on property where the dogs have plenty of room to roam around. I'm not kidding you on this. She says they are the happiest little bulldogs ever.

 

Marianne Russ Sharp
It just doesn't get any better. But did they still have any health issues at all?

 

Amy Quinton
They still have some mild incontinence but Sturges says they're able to lead normal bulldog lives.

 

Marianne Russ Sharp
I love it. So, Darla and Spanky are the first dogs to have this surgery and stem cell treatment but they are not the last right? We mentioned two other bulldogs, Myrtle, who has spina bifida and then there's Pippo who does not.

 

Amy Quinton
Right, and both of those bulldogs are part of a new clinical trial that Sturges is leading. One group with Pippo is the control group and another is having just surgery alone. And the third is having surgery plus the stem cell treatment.

 

Marianne Russ Sharp
You might ask though, why do we need a clinical trial if we already know this treatment worked on Darla and Spanky.

 

Amy Quinton
Right, well, Sturges wants to find out if there is a big difference between dogs who have surgery and dogs who have the surgery and the stem cell treatment. While they have seen some improvement with the surgery alone, it is unpredictable.

 

Marianne Russ Sharp
I see so the idea is really just to figure out what treatments work best on these dogs.

 

Amy Quinton
Sturges is doing a physical and neurological examination of the bulldog Pippo.

 

Beverly Sturges
Okay, so let's just finish our physical. I'm just gonna look in her mouth here.

 

Amy Quinton
Besides a little cold, Sturges isn't expecting to find anything wrong with Pippo since she's part of the control group in this trial, but she needs to compare a typical dog to one with spina bifida.

 

Beverly Sturges
We'll just palpate down her back here. On our spina bifida dogs, we can feel that she's missing some of the bony elements back by her tail, but Pippo feels pretty perfect.

 

Amy Quinton
Bulldogs with spina bifida can have both orthopedic and neurological problems. As part of the neurological exam. Sturgis needs to see if Pippo can perceive where her foot is when it's moved.

 

Beverly Sturges
So, I turned the paw over on the table here and our spina bifida dogs it'll stay, it'll stay turned over because of their abnormal neurological function. They don't know where their feet are in space. She's passing the test with flying colors.

 

Amy Quinton
Sturges says she's seen neurological improvement with some dogs in the trial. But she suspects even with stem cells some orthopedic problems might remain. But she's hopeful. Sturges is waiting for enough bulldogs to complete the clinical trial. At the very minimum, she says the trial is offering these little spina bifida bulldogs a chance of survival and adoption.

 

Beverly Sturges
We didn't just treat these puppies and then do away with them. We treated the puppies. Some of the puppies have done very well but others haven't done so well. All of them still have some degree of problems. And we found owners who are willing to take on these puppies that are not not normal and require daily care way above and beyond what a normal puppy will require.

 

Amy Quinton
And one of those owners is Katie Teykaerts and her Pampers-size-7-bulldog, Myrtle.

 

Katie Teykaerts
Know what we should have done. We should have brought your toys out, so you can show her your tug of war.

 

Amy Quinton
Katie adopted Myrtle knowing she had spina bifida and all the complications that come with it. She thinks Myrtle had repair surgery without the stem cell treatment. Still, Myrtle has made a lot of improvement.

 

Katie Teykaerts
She's pretty active. She just recently taught herself how to go up the stairs in our house. She used to drag her whole legs when she first came to us. And then she kind of got used to walking on her feet and she kind of built up that muscle.

 

Amy Quinton
The biggest difficulty in caring for Myrtle is her incontinence, because it makes her susceptible to urinary tract infections, or UTIs.

 

Katie Teykaerts
She has chronic UTIs because of the diaper wearing. She's on antibiotics, probably quarterly, at least. She might already becoming resistant to the first one that we've been using. But that's kind of just the routine with these dogs is the UTIs.

 

Amy Quinton
And the constant diaper changing. But Katie had no problem tackling those complications. She's a speech pathologist and has clients with spina bifida.

 

Katie Teykaerts
Any chance for that increased independence, because my kids with spina bifida are just, they're so active, they just want to like communicate and do what everyone else is doing. And so the idea that this surgery can kind of provide that to them is huge.

 

Marianne Russ Sharp
That's a story with a happy ending.

 

Amy Quinton
And I have to say Myrtle is the sweetest dog. Katie shared a photo with us of Myrtle when she was just a puppy. You can have a look at it on our website at ucdavis.edu/unfold. She's got little like, Myrtle has little suspenders like little rainbow suspenders, with the diapers. It's very cute.

 

Marianne Russ Sharp
Okay, gotta check that one out. Okay, so now that we know that the stem cell treatment worked on sheep, and dogs, people are next, right?

 

Amy Quinton
Yeah, the results are compelling enough that the FDA gave its approval to launch the world's first human clinical trial using stem cells before birth to treat the most serious form of spina bifida.

 

Marianne Russ Sharp
And that is taking place right now at ºÙºÙÊÓƵ Health.

 

Amy Quinton
And we're going to tell you that story in the next episode of Unfold. You can check out all of our Unfold episodes including past seasons on our website. I'm Amy Quinton.

 

Marianne Russ Sharp
And I'm Marianne Russ Sharp. Thanks so much for listening.

 

Amy Quinton
Unfold is a production of ºÙºÙÊÓƵ. Original music for Unfold comes from Damien Verrett and Curtis Jerome Haynes. Additional music comes from Blue Dot Sessions.

 

Marianne Russ Sharp
If you like Unfold, leave us a review because reviews can help more people like you find our show and enjoy it. So write your review on Apple podcasts or leave a rating for us on Spotify or anywhere you listen to podcasts. Thanks for helping this show grow.