Three babies have been born after receiving the world’s first spina bifida treatment combining surgery with stem cells. This was made possible by a landmark clinical trial at UC Davis Health.
The one-of-a-kind treatment, delivered
while a fetus is still developing in the mother’s womb, could improve outcomes
for children with this birth defect.
Launched in the spring of 2021, the clinical trial is
known formally as the “CuRe Trial:
Cellular Therapy for In Utero Repair of Myelomeningocele.” Thirty-five patients
will be treated in total.
The three babies from the trial that
have been born so far will be monitored by the research team until 30 months of
age to fully assess the procedure’s safety and effectiveness.
The first phase of the trial is funded by a $9 million
state grant from the state’s stem cell agency, the California Institute for
Regenerative Medicine (CIRM).
“This clinical trial could enhance the
quality of life for so many patients to come,” said Emily, the first clinical
trial participant who traveled from Austin, Tex. to participate. Her daughter
Robbie was born last October. “We didn’t know about spina bifida until the
diagnosis. We are so thankful that we got to be a part of this. We are giving
our daughter the very best chance at a bright future.”
Spina bifida,
also known as myelomeningocele, occurs when spinal tissue fails to fuse
properly during the early stages of pregnancy. The birth defect can lead to a
range of lifelong cognitive, mobility, urinary and bowel disabilities. It
affects 1,500 to 2,000 children in the U.S. every year. It is often diagnosed
through ultrasound.
While surgery performed after birth can
help reduce some of the effects, surgery before birth can prevent or lessen the
severity of the fetus’s spinal damage, which worsens over the course of
pregnancy.
“I’ve been working toward this day for almost 25 years now,” said Diana Farmer, the world’s first woman fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator on the study.
The path to a future cure
As a leader of the Management of Myelomeningocele Study (MOMS) clinical trial in the early 2000s, Farmer had
previously helped to prove that fetal surgery reduced neurological deficits
from spina bifida. Many children in that study showed improvement but still
required wheelchairs or leg braces.
Farmer recruited bioengineer Aijun Wang specifically
to help take that work to the next level. Together, they launched the UC Davis Health Surgical Bioengineering Laboratory to find ways to use stem cells and
bioengineering to advance surgical effectiveness and improve outcomes. Farmer
also launched the UC Davis Fetal Care and Treatment Center with fetal surgeon Shinjiro Hirose and
the UC Davis Children’s Surgery Center several years ago.
Farmer, Wang and their research team
have been working on their novel approach using stem cells in fetal surgery for
more than 10 years. Over that time, animal modeling has shown it is capable of
preventing the paralysis associated with spina bifida.
It’s believed that the stem cells work
to repair and restore damaged spinal tissue, beyond what surgery can accomplish
alone.
Preliminary work by Farmer and Wang
proved that prenatal surgery combined with human placenta-derived mesenchymal
stromal cells, held in place with a biomaterial scaffold to form a “patch,”
helped lambs with spina bifida walk without noticeable disability.
“When the baby sheep who received stem
cells were born, they were able to stand at birth and they were able to run
around almost normally. It was amazing,” Wang said.
When the team refined their surgery and
stem cells technique for canines, the treatment also improved the mobility of
dogs with naturally occurring spina bifida.
A pair of English bulldogs named Darla
and Spanky were the world’s first dogs to be successfully treated with surgery
and stem cells. Spina bifida, a common birth defect in this breed, frequently
leaves them with little function in their hindquarters.
By their post-surgery re-check at 4 months old, Darla and Spanky were able to walk, run and play.
The world’s first human trial
When Emily and her husband Harry learned
that they would be first-time parents, they never expected any pregnancy
complications. But the day that Emily learned that her developing child had
spina bifida was also the day she first heard about the CuRe trial.
For Emily, it was a lifeline that they
couldn’t refuse.
Emily with Diana Farmer and baby Robbie.
Participating in the trial would mean
that she would need to temporarily move to Sacramento for the fetal surgery and
then for weekly follow-up visits during her pregnancy.
After screenings, MRI scans and
interviews, Emily received the life-changing news that she was accepted into
the trial. Her fetal surgery was scheduled for July 12, 2021, at 25 weeks and
five days gestation.
Farmer and Wang’s team manufactures
clinical grade stem cells – mesenchymal stem cells – from placental tissue in
the UC Davis Health’s CIRM-funded Institute for Regenerative Cures. The cells
are known to be among the most promising type of cells in regenerative
medicine.
The lab is a Good Manufacturing Practice (GMP) Laboratory for safe use in humans. It is
here that they made the stem cell patch for Emily’s fetal surgery.
“It’s a four-day process to make the stem cell patch,” said Priya Kumar, the scientist at the Center for Surgical Bioengineering in the Department of Surgery, who leads the team that creates the stem cell patches and delivers them to the operating room. “The time we pull out the cells, the time we seed on the scaffold, and the time we deliver, is all critical.”
A first in medical history
During Emily’s historic procedure, a
40-person operating and cell preparation team did the careful dance that they
had been long preparing for.
After Emily was placed under general
anesthetic, a small opening was made in her uterus and they floated the fetus up
to that incision point so they could expose its spine and the spina bifida
defect. The surgeons used a microscope to carefully begin the
repair.
Then the moment of truth: The stem cell
patch was placed directly over the exposed spinal cord of the fetus. The fetal
surgeons then closed the incision to allow the tissue to regenerate.
“The placement of the stem cell patch
went off without a hitch. Mother and fetus did great!” Farmer said.
The team declared the first-of-its-kind surgery a success.
Delivery day
On Sept. 20, 2021, at 35 weeks and five
days gestation, Robbie was born at 5 pounds, 10 ounces, 19 inches long via
C-section.
“One of my first fears was that I
wouldn’t be able to see her, but they brought her over to me. I got to see her
toes wiggle for the first time. It was so reassuring and a little bit out of
this world,” Emily said.
This experience has been larger than
life and has exceeded every expectation. I hope this trial will enhance the
quality of life for so many patients to come.”—Emily
For Farmer, this day is what she had
long hoped for, and it came with surprises. If Robbie had remained untreated,
she was expected to be born with leg paralysis.
“It was very clear the minute she was
born that she was kicking her legs and I remember very clearly saying, ‘Oh my
God, I think she’s wiggling her toes!’” said Farmer, who noted that the
observation was not an official confirmation, but it was promising. “It was
amazing. We kept saying, ‘Am I seeing that? Is that real?’”
Both mom and baby are at home and in
good health. Robbie just celebrated her first birthday.
The CuRe team is cautious about drawing
conclusions and says a lot is still to be learned during this safety phase of
the trial. The team will continue to monitor Robbie and the other babies in the
trial until they are 6 years old, with a key checkup happening at 30 months to
see if they are walking and potty training.
“This experience has been larger than life and has exceeded every expectation. I hope this trial will enhance the quality of life for so many patients to come,” Emily said. “We are honored to be part of history in the making.”
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