New treatment inside the womb could save thousands of babies, scientists say

Several key trials are underway to test surgical and medical treatments that allow doctors to treat conditions in babies before they are born

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About 1.400 babies with spina bifida are born in the US every year, Photo: UC Davis Health
About 1.400 babies with spina bifida are born in the US every year, Photo: UC Davis Health
Disclaimer: The translations are mostly done through AI translator and might not be 100% accurate.

Cutting-edge therapies that treat fetuses with neurological defects have the potential to change birth care as we know it.

Michelle Johnson's fourth pregnancy was going according to plan until the specialist, who was performing a standard 20-week ultrasound scan, stiffened slightly while pressing on her stomach.

The sonographer was "really uncomfortable," Johnson recalled, asking questions in confusion.

A few days later, the head of radiology called her.

His tone was serious as he chose his words and said that it was rare in his experience, but Johnson needed to see a gestational-fetal medicine specialist immediately because her child had spina bifida.

Scientifically known as myelomeningocele, spina bifida is when the spinal cord, which in children begins to develop as a cannoli-shaped tube and includes the nervous system, does not close completely.

The superhighway of nerves thus flows into a small bulge somewhere along the spine.

This birth defect of the nervous system can lead to lifelong cognitive problems as well as chronic immobility and paralysis from the hips down.

"It was devastating," says Johnson, who was 35 at the time and living in Portland, Oregon, in the US.

"I was in shock," she adds.

It is born in the USA every year about 1.400 babies with spina bifida.

The exact cause of this complex condition is not fully known, but it is assumed to be a combination of genetic and environmental factors.

A low level of folic acid intake during pregnancy or certain anti-epileptic drugs can influence the development of this condition, but it is not clear exactly how big a role they play.

Spina bifida is usually treated within 24 to 48 hours of birth: surgeons sew the spinal cord back into the baby's body, preventing the condition from worsening.


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But while making an appointment with a specialist, a nurse told Johnson over the phone about a new program in California that uses stem cells to treat children with spina bifida while they're still in the womb.

If she decided to participate in the program, her baby would be the second human patient ever to undergo this type of treatment.

Johnson knew this was the chance she wanted to give her unborn child.

Because the procedure had to happen before the 26th week of pregnancy, "it was like a race against time," Johnson says.

After several scans, blood tests and conversations, she embarked on something larger than life.

Prenatal screening for neurological conditions has made tremendous progress over the past few decades.

This technology includes genetic analysis, neuroimaging and high-resolution fetal magnetic resonance imaging.

They help doctors peer into the developing fetus's nervous system and diagnose any life-changing conditions that will befall them as soon as they are born, earlier and more often.

But during all that progress, there wasn't much that doctors could do about those diagnoses until after the child left the womb, but significant a percentage of key brain development occurs long before a baby is born.

Now a new wave of pioneering in-utero neuroscience therapies is helping to change that.

Several key trials are underway to test surgical and medical treatments that allow doctors to treat conditions in babies before they are born.

The field is "on the very edge" of a whole new dimension of therapy, says Jeffrey Russ, a pediatric neurologist at Duke University who recently wrote an academic essay on in-utero treatment as the "next frontier" of neurology.

One of those revolutionary treatments is the current first clinical trial approved by the US Food and Drug Administration (FDA), which treats spina bifida in the uterus with the help of placental stem cells.

The project, known as Where did it last(CuRe Trial), is the culmination of 25 years of work as a fetal surgeon Diana Lee Farmer, from the University of California, Davis.

Intrauterine surgeries, during which the opening in the spinal cord is sewn back up, have become standard care in cases with very severe spina bifida.

They slow the progression of the disease during pregnancy and improve the patient's outlook more than postpartum surgery, as indicated by the results of Dijana Li Farmer's many years of work.

But with a new project she wants to go one step further.

Suturing the open neural tube would be done with stem cells from parts of the mother's placenta, known as "mesenchymal stromal cells", derived and grown in a meticulously precise four-day process.

They should actively step in and repair the damage that has already occurred by the time of diagnosis.

These stem cells are "very smart," he says Aidžun Vang, the bioengineer who developed this stem cell technology for the Kjur trial.

"They can protect neurons from dying in the environment," he adds.

Preliminary data from this experiment on lambs with spina bifida showed that the treatment allows them to hop around without noticeable disability, when they would otherwise be paralyzed in their hind legs.

The same was observed when the procedure was applied to bulldozers.

UC Davis

More than 30 people were in the operating room when Michelle Johnson, just one day shy of the 26-week mark, became the second patient to undergo this operation.

An incision was made on her stomach in the shape of a watermelon, the uterus was almost entirely pulled out of the body, and the fetus was floated to the opening of the uterus.

This allowed doctors to reach the herniated disc in the baby's tiny spine and delicately create a patch with stem cells.

Doctors used a special microscope to perform the procedure because the baby was so small.

If the child, a boy who would later be named Tobajas, had not been treated, he would have been born paralyzed from the hips down.

On February 2022, 3,5, he was born by caesarean section, weighing XNUMX kilograms, wiggling his legs and curling his toes.

"It felt like we'd won the lottery," says Johnson.

Tobajas will have to be monitored until he is 30 months old.

Its final live review is scheduled for this summer, before the procedure is officially declared completely safe and effective for the purposes of the experiment.

Doctors will most likely continue to monitor him until he is at least five years old.

At the time of writing, 10 more patients have undergone Cure treatment, and Diana Lee Farmer's team has secured $15 million in funding for 29 more patients, with hopes of treating a dozen patients a year.

Only in 2028 will the team led by Farmer be able to review all the collected data and confirm whether this new therapy can become the standard for children across the country.

"I hope we can achieve a very significant improvement in outcomes for these children with spina bifida," Farmer says.

"But as with any good science project, you answer one question and that opens the door to new questions," he adds.

This is cutting-edge science for anatomical conditions that can be surgically repaired, according to Ras.

But a new revolution in which in-utero therapies may have the potential to reverse neurological conditions in newborn babies is taking place where therapies can be delivered at the molecular or genetic level.

It's a "completely new concept" that will "open up a whole new world," says Ras.

His colleagues at Duke University contributed to the design of the protocol for the first-ever in utero treatment for Pompe disease, a rare genetic disease that causes cells to stick to overly complex sugars, leading to neurological conditions, breathing problems, heart problems and muscle weakness.

Most patients die within a year or two of birth.

Because Pompe disease is caused by a deficiency of an enzyme called acid alpha-glucosidase, it is usually treated with enzyme replacement therapy (ERT), where children receive regular injections of the enzyme.

As with spina bifida, the data show that starting ERT as soon as the baby is born can improve symptoms, but it cannot completely stop the occurrence of the disease.

When doctors at the Ottawa Hospital in Ontario, Canada, performed tests on the unborn baby girl Ajla Bashir in February 2021, announcing that she had inherited the same genes that led to her two sisters Zara and Sara being diagnosed with Pompe disease after birth, they knew they had to act quickly.

Both Zara and Sara died, one at 29 months and the other at eight.

But with Aileen's diagnosis in utero, the medical team was able to intervene earlier.

On March 2021, 24, doctors gave Ajla her first dose of enzyme replacement while she was still in her mother's womb at XNUMX weeks and five days of development.

They injected a liquid formula with a copy of the missing enzyme called alglucosidase alfa into the umbilical vein.

This approach allows the engineered enzyme to make its way into the bloodstream of the fetus while it is still developing.

He barely notices the medicine as something foreign to him and does not have a strong immune reaction that can occur during treatment after birth.

Six more infusions every two weeks followed.

Ajla was born on June 22, 2021 and has been receiving enzyme injections every week since then.

"She is a very happy, agile three-year-old who meets all her neurodevelopmental thresholds," he says Karen Fung-Ki-Fung, a specialist in fetal medicine at the Ottawa Hospital who treated her.

"I was just watching a video of her jumping up and down," she adds.

CHEO Media House

Similar to Tobajas, doctors will continue to monitor Ayla for at least five more years to monitor the disease's progress, as the therapy does not completely prevent irreversible organ damage.

But Ajla's story paves the way for startups prenatal medical treatments which intervene on disorders such as these with one simple injection.

"We hoped to change the paradigm so that we could treat genetic diseases," he says Tippy Mackenzie, one of the fetal surgeons at the University of California, San Francisco who led the development of the protocol used to treat Ayla.

Several types of treatment are currently offered to newborns that could potentially be offered during the fetal stage, McKenzie says.

It launched an ongoing five-year clinical trial on total 10 patients in California to help officially establish in utero ERT as an approved procedure for Pompe disease and other rare diseases such as Neuronopathic Gaucher disease, Mucopolysaccharidosis and Wolman disease.

Two babies with mucopolysaccharidosis have already been treated as part of the trial and "the news is positive," Mackenzie says.

They continue to accept patients for the trial treatment, which is open to international patients.

Developing fetal treatments for conditions like these would also help highlight the need for more testing for genetic diseases in general, McKenzie says.

"Diagnosis and treatment, I call them ying and yang, they go together," he adds.

While enzyme replacement is the least invasive type of treatment for genetic disorders and requires multiple doses throughout the patient's life, this new method could be adapted to other controversial genetic therapy to alter DNA unborn babies either by cutting out the defective gene or replacing the missing one.

Maurice Ramirez/UCSF

Tippi McKenzie's work "lays the groundwork for these types of advanced therapies in the future," he says To William Parenteau, professor of surgery at the Children's Hospital of Philadelphia.

"If those trials prove useful in treating disease before birth with enzyme replacement therapy, then the next question is more definitive therapy such as gene editing in the womb," he adds.

In a series of groundbreaking experiments, Peranto used the Crispr genome-editing technique to tweak the genetic code of several mice still in the womb and cured them of a genetic skin disease, a lung disease, and a genetic metabolic disorder that affects the liver of rodents.

How long it will take before gene-editing therapies reach human trials is very difficult to say, and "it always takes longer than we want or expect," Peranto says.

Maybe five to 10 years.

"It's just a matter of working hard at it," he says.

As these trials gather momentum, consideration of the ethical and practical implications of these advances will be a priority.

"We're going to have to start with really concrete examples, where it's very clear that the benefits outweigh the risks," Ras says.

Obviously not all conditions can and should not be treated with stem cells, enzyme replacement and gene editing technology before birth.

It's too early to acquire a clear picture of the long-term effects of these treatments in the womb.

Most patients from these in utero trials are still babies or very young children.

There is also no long-term data from adult parents who are currently undergoing gene-altering therapies.

While surgical procedures and chemical therapies such as those developed by Farmer and McKenzie are mostly short-term procedures, once doctors make genetic changes in an unborn child, these changes and their consequences will remain forever.

Most importantly, therapies in the womb are unique procedures with double risk and stakes, because they involve both the mother and her unborn child, says Ras.

"You're not treating just one patient, but two," he adds.


The Johnson family traveled back to California a little more than a year after the procedure.

Johnson also met other mothers from the Cure trial, and hospital staff took turns coming to say hello, play with Tobajas in the yard, bring him cake and candles to celebrate his first birthday.

"It was really special.

"It came full circle for them to see all the work they do and to meet the miracle of a baby and see how healthy and happy she is," Johnson says.

At the time of writing this article, Tobajas is more than two years old and walking.


See what life looks like for parents of children with rare diseases


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