Spina bifida is the most common cause of lifelong childhood paralysis in the United States; approximately four children are born with this spinal defect every day. Standard care usually involves surgery, but it still leaves more than half of children unable to walk. But a combination of surgery and stem cell treatment may offer hope to children. In this episode of Unfold, we examine the world’s first human clinical trial using stem cells before birth to treat the most serious form of the condition.
In this episode:
, pediatric surgeon and chair of surgery at ºÙºÙÊÓƵ Health
, medical director of the Shriners Spina Bifida program and associate professor in the department of Physical Medicine and Rehabilitation at ºÙºÙÊÓƵ
Michelle Johnson, mother of baby enrolled in spina bifida clinical trial
Jeff Maginnis, father of baby enrolled in spina bifida clinical trial
Transcript
Transcriptions may contain errors.
Amy Quinton
Michelle Johnson was 20 weeks pregnant with her second child, when she got a phone call about her ultrasound that left her shaken.
Michelle Johnson
Just in the clinician’s voice. You know, it was not a good call. And he had just said, "Is this a good time? You know, are you available to talk?" And then, he said he wanted to talk about the results of the ultrasound and that based on the abnormalities they were seeing it was indicative of spina bifida.
Amy Quinton
In tears, she immediately called her boyfriend and the baby's father, Jeff Maginnis, at work.
Jeff Maginnis
I could hear in her voice that she was concerned and, you know, very upset. And so, I left work and came home, and you know, we talked about it. And that's, I think, when I learned that it was a lot more severe than the phone call might have led on to be.
Amy Quinton
The Portland, Oregon couple spent the next few days researching what the diagnosis meant, and what treatment options they might have. What did you know about spina bifida?
Michelle Johnson
Nothing. Very little to nothing.
Jeff Maginnis
Nothing for me, yeah.
Michelle Johnson
Yeah, I think I knew, I knew it was a defect of the spine, and that it could impact walking. So, I guess I knew briefly of spina bifida but not specifics. And I was just in shock. You know, I, I had no idea what the right answer was or what outlet to pursue. So, it was it was surreal.
Amy Quinton
Michelle and Jeff's developing baby had myelomeningocele, the most severe form of spina bifida. Paralysis, incontinence and excess fluid in the brain were all possibilities. But they soon heard about a trial testing a new stem cell treatment and prenatal surgery at ºÙºÙÊÓƵ Health. They learned it might prevent the most severe conditions. While it had never been tested on humans, they decided to participate.
Michelle Johnson
What won't you do for your child, unborn or born? You're going to do everything you can.
Amy Quinton
In this episode of Unfold, you'll hear about their journey through the world's first human clinical trial that's providing hope for a spina bifida cure. 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
I'm Marianne Russ Sharp. This story is about the groundbreaking work of pediatric surgeon Diana Farmer with ºÙºÙÊÓƵ Health.
Amy Quinton
It's also about the courage of families taking part in the world's first clinical trial to treat spina bifida through prenatal surgery and stem cell treatment.
Marianne Russ Sharp
Spina bifida is when the fetus’s spinal cord doesn't develop properly in the womb. Part of the spinal cord and the surrounding tissues are exposed through a gap in the backbone.
Amy Quinton
Farmer says four children in the United States are born with spina bifida every day, and it can leave children paralyzed.
Diana Farmer
The severity can be variable based on where in the spinal cord the defect develops. So, if it's in the cervical, in the neck area, then a person might be paralyzed from the neck down. If it's in the back area, you might just be paralyzed from the legs down.
Marianne Russ Sharp
Farmer actually pioneered the prenatal surgery to close the exposed spinal cord. It doubled the chances a child would walk and decreased the likelihood that a child would develop excess fluid in the brain, called hydrocephalus.
Amy Quinton
Now researchers have designed the first human clinical trial to see whether engineered placental stem cells combined with prenatal surgery can do even more.
Marianne Russ Sharp
Surgeons will close the developing baby's exposed spinal cord and then use a special stem cell patch. The stem cells are engineered to protect neurons, or nerve cells, from damage.
Amy Quinton
And as we mentioned in the last episode of Unfold, the procedure was successful on lambs with spina bifida. It allowed them to walk.
Marianne Russ Sharp
And in 2017, ºÙºÙÊÓƵ veterinary surgeons were able to successfully treat spina bifida in two English bulldogs named Darla and Spanky, using this same procedure.
Amy Quinton
Darla and Spanky can now walk and run. Farmer says the bulldogs shed light on a few things about this procedure, especially given the dog's age much faster than humans.
Diana Farmer
The pets Darla and Spanky allowed us to see that there appears to be durability to this therapy.
Marianne Russ Sharp
The FDA has given doctors approval to conduct a safety trial also called a phase one trial
Amy Quinton
And a safety trial probably sounds a bit scary.
Marianne Russ Sharp
It does sound scary, but it's actually standard.
Amy Quinton
Well, it was scary for Michelle Johnson and Jeff Maginnis. Before Michelle even considered participating, she had to weigh all the risks and options and she had several, including a much less invasive laparoscopic surgery, without stem cells.
Michelle Johnson
Laparoscopic has much less risks to the mom. You're not going to be at high risk for ruptured uterus, you can have subsequent pregnancies, but laparoscopic didn't offer the stem cells. And if you do any research on the last decade of stem cell studies with animals, it's really black and white. You know, the animals that receive stem cells are able to walk at birth and the ones that don't, don't walk at birth.
Marianne Russ Sharp
So, Michelle had really done her homework on the lamb studies. Did she know about Darla and Spanky, too?
Amy Quinton
Yeah, Michelle says the animal studies gave both of them hope that the surgery could work.
Michelle Johnson
I knew there were more increased risks. But with what we knew, we felt that it was just the best, the best decision to go forward. I don't think we felt like we had anything to lose.
Amy Quinton
Jeff says they just wanted to do what was best for their baby.
Jeff Maginnis
It's scary. You know, I mean, "what happens if" is always, you know, in the back of your mind, but I think that, you know, as soon as we spent those four days kind of doing our research and learning, I think that we decided that, you know, there was no question in our mind that that was the program that ºÙºÙÊÓƵ had.
Marianne Russ Sharp
In order to take part in a clinical trial, moms have to first meet a lot of qualifications and go through a number of tests that included an MRI for Michelle. And remember, Michelle was 20 weeks pregnant when she got the news.
Michelle Johnson
So, you can only pursue gestational surgery for up to 26 weeks and after that you're no longer a candidate. And at this point, I was 21 to 22 weeks. So, we were running out of time. And these MRIs were booked out three to six weeks in Oregon.
Amy Quinton
So, she came to ºÙºÙÊÓƵ Health.
Michelle Johnson
We had to drop everything, our careers, our plans. I mean, it was all hands-on deck. We've only got four weeks to work with, what are we going to do.
Amy Quinton
Time was running out to make this major life decision.
Diana Farmer
And a woman has to they have to move here because this is a big deal right now for this trial, because the FDA wants them close by if there was some problem to happen, so we have to be able to follow them weekly during their pregnancy.
Marianne Russ Sharp
So, she and Jeff up ended their lives in Portland and moved to Sacramento that could not have been an easy decision.
Amy Quinton
No and what made it more difficult, Michelle and Jeff have two school-aged children from previous marriages. They had to leave them with their former spouses in order to move to Sacramento.
Marianne Russ Sharp
Wow.
Michelle Johnson
That was a huge sacrifice. I mean, my career potentially, how our older kids stay in Portland and function and succeed in school without us and how we can juggle that. And so, we were willing to risk all of that, in hopes that our child could walk.
Marianne Russ Sharp
The surgical team operated on the first clinical trial participant in July of last year.
Amy Quinton
Farmer says the entire team tried to think of the operation as just another surgery. It would be another 10-week wait until the baby was born. For Farmer that moment was the culmination of 10 years of research.
Diana Farmer
I will. I will admit I was just I broke into tears.
Amy Quinton
The baby seemed healthy.
Diana Farmer
The back was closed. There didn't appear to be complications. And it was like oh my god, you know, we did it.
Amy Quinton
About three months later, it was Michelle's turn. Surgeons performed a cesarean section to attach the stem cell patch to the developing baby's spinal cord and then close the back. Michelle's surgery was successful. But her recovery was tough, really tough.
Michelle Johnson
It's a more invasive C section, it's much larger, and it's really hard to heal when you have something growing inside of you. So as much as I'd try and rest it was extremely uncomfortable and every kick or movement from the baby would put me in a lot of pain.
Amy Quinton
Women who have prenatal surgery also have a high risk of a ruptured uterus during labor.
Marianne Russ Sharp
So, at 36 weeks, Michelle had another C section. That's considered pre-term.
Amy Quinton
And that second C section when Michelle and Jeff would meet their baby came on February 1. Doctors brought Jeff into the delivery room to make the big announcement.
Jeff Maginnis
They summoned me over for my job to tell everybody if it was a boy or a girl. We waited for the whole entire pregnancy to find out that he was a boy. And so, they lifted him up and one of our favorite pictures of Tobi is that exact moment right there and there's a, it was a very magical moment finding out that we were having a boy, or we had had a boy.
Michelle Johnson
When they held Tobi up on the other side of the curtain, it was like holding up Simba in The Lion King when he was born. And that's, we call it our Lion King photo we have this great picture of Tobi just being held up and...
Jeff Maginnis
The lights are just
Michelle Johnson
Right on him.
Jeff Maginnis
Spot on. Spotlight right on Tobi, and then Tobi's just all in the light right there and yeah, that's his Pride Rock moment.
Michelle Johnson
Yeah
Marianne Russ Sharp
And it is an amazing photo. It's just beautiful. And you can see it if you'd like on our website that's uc davis.edu/unfold.
Amy Quinton
So, Tobias "Tobi" Maginnis was born weighing a healthy seven pounds and 13 ounces.
Michelle Johnson
He was born with his legs kicking and toes wiggling. The MRI showed no brain inflammation, no hydrocephalus, which was a miracle for us. You know, as far as we know, the procedure worked. Although it will take time as he develops and becomes of walking age to definitively know. As far as we can tell, he's very healthy and great. So
Jeff Maginnis
It hurts when he kicks so we have some hope there.
Michelle Johnson
Yeah
Amy Quinton
Michelle and Jeff brought Tobi back to ºÙºÙÊÓƵ Health for his three-month checkup. They met Dr. Maya Evans who specializes in pediatric rehabilitation.
Maya Evans
And what do you guys notice as far as leg movements?
Michelle Johnson
Great. They kick. He's ticklish. His toes wiggle.
Maya Evans
Great. So, no weakness detected?
Michelle Johnson
No.
Maya Evans
Okay, good. Good. Good.
Amy Quinton
Tobi has reddish blond hair and blue eyes and is sporting a onesie with little carrots on it. Evans lays him down on an exam table to try to get him to do a number of movements to test his motor skills.
Maya Evans
I am trying to get his quads so to kick up, kick out at the knees. Let's check. Oh yeah, quad, quad, quad quad. Kick, kick, kick. Oh, that was a good one. Kick. Kick. This one.
Amy Quinton
She rolls over on his tummy to test his glutes or his little booty muscles as she calls them.
Maya Evans
That's really good. Okay. Then we're going to try to get your booty. That's going to be a little tricky. It's hard for Dr. Evans to feel everything. That's good.
Amy Quinton
Evans then test Tobi's hamstrings, which are difficult to assess on a three-month-old, but Tobi is being a little trooper through it all.
Maya Evans
I feel like your hamstrings are very strong. It's just hard for me to fight against them. You know, like to really like, you know, if he could kick straight, I could really push against it. When he bends it, I just never got a good one. But it's okay if you don't want to do it. You don't. Okay, that was good. Okay. I'll take it. I'll take it. I am done. You were very good. You're gonna go rest now. You going to take a nap.
Amy Quinton
After both morning and afternoon sessions of testing his motor skills and flexibility, Tobi is tuckered out. But Tobi's dad, Jeff, couldn't be prouder.
Jeff Maginnis
But it sounded like he tested in the 75 percentiles. So, I mean, I think you know, even for a preemie, I'd say that's very exciting. So.
Amy Quinton
Doctors stress, it's too early to know whether Tobi could still experience developmental delays, or complications as a result of spina bifida. The incontinence that often comes with spina bifida is hard to gauge at Tobi's age, although Michelle says he will likely have to catheterize the rest of his life.
Michelle Johnson
Sometimes I worried about that, you know, what does that look like for a seven-year-old? What does that look like for a 12-year-old? What does that look like for an adult? But it's, it's minimal compared to not having the ability to walk you know. Catheterization is, is much more manageable than then many other ailments so I put my worries aside for now, and we'll tackle it when the time comes.
Amy Quinton
But some of the bladder and bowel issues that come with spina bifida could improve because of this procedure. And although it's not certain, Diana Farmer is hopeful.
Diana Farmer
I think it's possible that we could completely reverse the damage that has already been done as well as preventing more damage, such that we might not only improve the spinal cord level but include all the way down to bowel and bladder function. I mean, that's, that's the goal. That's the hope.
Amy Quinton
Tobi's last appointment of the day is less of an appointment and more of a reunion, with Farmer.
Diana Farmer
Oh my gosh, who is this huge person. Oh, my gosh, I haven't seen you since you were like this big.
Amy Quinton
Farmer immediately picks up Tobi and holds him in her arms. She gently touches the soft spot on his head.
Diana Farmer
Nice soft fontanelle, that soft spot, you know. So that's always that's also a good sign. What's nice for us doctors, it's a hint into what's going on underneath. And so, if it was bulging, we'd be worried about it. That he had fluid on the brain. So, when it's kind of sunken in and soft, it's like, perfect. So, you got that for sure. And then we're pretty excited about these wiggly legs. Yeah.
Amy Quinton
Besides the scar on his back from prenatal surgery, it's tough to see any difference between Tobi and any other three-month-old. Tobi's mom, Michelle, thinks he's perfect.
Michelle Johnson
We were saying how his first laugh he was five days old when we were discharged. And I was holding him, and he went, "ha, ha, ha." And I said, "Did you hear that? He just laughed." I said, "We all need some stem cells." These things are great. He's the happiest baby. He's just always laughing and happy and content.
Diana Farmer
I'd be happy to take credit for that.
Michelle Johnson
It's the stem cells.
Marianne Russ Sharp
It's so moving to hear about these women going through this trial. They're really brave.
Amy Quinton
Yeah, Farmer says if clinical trials like this one succeed moving forward, it might mean that children having to use wheelchairs as a result of spina bifida could be a thing of the past.
Marianne Russ Sharp
It's just incredible. We should also mention that there's another positive aspect of this trial. And that is where the research is headed next.
Amy Quinton
I know they're hoping to perform the same operation and use the stem cells on spina bifida babies after they're born. Farmer says it may not have the same effects, but it could still offer some improvement.
Marianne Russ Sharp
But wait, there's more. Believe it or not, there's another hopeful aspect to all of this. And that has to do with the placental stem cells that were engineered by Dr. Aijun Wang. We heard from him in the last episode. He is researching whether the stem cells also have the potential to help people with other neurological diseases, maybe even those with acquired spinal cord injuries, such as from an accident.
Amy Quinton
That would be a remarkable next chapter. And in the meantime, you can listen to more Unfold episodes, and you can check out our first episode on spina bifida at our website and see photos of Michelle Johnson and Jeff and Tobi Maginnis at ucdavis.edu/unfold.
Marianne Russ Sharp
And don't forget, we've even got that photo they described as the Lion King moment there. It is awesome.
Amy Quinton
Definitely worth checking out. Thanks for listening. I'm Amy Quinton.
Marianne Russ Sharp
And I'm Marianne Russ Sharp.
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.
If you liked this podcast, check out ºÙºÙÊÓƵ's other podcast The Backdrop. It's a monthly interview program featuring conversations with ºÙºÙÊÓƵ scholars and researchers working in the social sciences, humanities, arts and culture. Hosted by public radio veteran Soterios Johnson, the conversations feature new work and expertise on a trending topic in the news. Subscribe wherever you get your podcasts.