Groundbreaking trial aims to reverse paralysis and other abnormal functions of spina bifida before birth

Three babies have been born after receiving the world’s first spina bifida treatment combining surgery and stem cells. This was made possible by a landmark clinical trial at UC Davis Health.

The unique treatment, given 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 officially known as the “CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele”. Thirty-five patients will be treated in total.

The three babies in the trial who have been born so far will be followed by the research team until they are 30 months old to fully assess the safety and effectiveness of the procedure.

The first phase of the trial is funded by a $9 million grant from the state stem cell agency, the California Institute for Regenerative Medicine (CIRM).

“This clinical trial could improve the quality of life for so many future patients,” said Emily, the first clinical trial participant who traveled from Austin, Texas to participate. His daughter Robbie was born last October. “We didn’t know about spina bifida before the diagnosis. We are so grateful to have been able to be part of it. We are giving our daughter the best chance for 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 cause a series of cognitive, motor, urinary and intestinal disorders throughout life. It affects 1,500 to 2,000 children in the United States each year. It is often diagnosed by ultrasound.

While surgery after birth can help reduce some of the effects, surgery before birth can prevent or lessen the severity of damage to the fetal spine, which worsens during pregnancy.

“I’ve been working to date for almost 25 years now,” said Diana Farmer, the world’s first female fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator of 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 prove that fetal surgery reduced the neurological deficits of spina bifida. Many children in this study showed improvement but still needed wheelchairs or leg braces.

Farmer recruited bio-engineer Aijun Wang specifically to help take this work to the next level. Together, they launched the UC Davis Health Surgical Bioengineering Lab to find ways to use stem cells and bioengineering to advance surgical efficiency and improve outcomes. Farmer also started 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 over 10 years. During this period, animal modeling has shown that it is able to prevent the paralysis associated with spina bifida.

Stem cells are thought to work to repair and restore damaged spinal tissue, beyond what surgery alone can accomplish.

Preliminary work by Farmer and Wang proved that prenatal surgery combined with mesenchymal stromal cells derived from the human placenta, held in place with a biomaterial scaffold to form a “patch”, helped lambs with spina bifida walk without disability. noticeable.

“When the baby sheep who received stem cells were born, they were able to stand at birth and they could run almost normally. It was amazing,” Wang said.

When the team refined their canine surgery and stem cell technique, the treatment also improved the mobility of dogs with naturally occurring spina bifida.

Two English bulldogs named Darla and Spanky were the first dogs in the world to be successfully treated with surgery and stem cells. Spina bifida, a common birth defect in this breed, often leaves them with little function in their hindquarters.

On their post-operative 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 found out they would be first-time parents, they didn’t expect any pregnancy complications. But the day Emily learned her developing child had spina bifida was also the day she first heard about the CuRe trial.

For Emily, it was a lifeline they couldn’t refuse.

Participating in the trial would mean she would have to temporarily move to Sacramento for fetal surgery and then for weekly follow-up visits during her pregnancy.

After screenings, MRIs and interviews, Emily received the life-changing news that she had been 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 is making clinical-grade stem cells — mesenchymal stem cells — from placental tissue in the CIRM-funded Institute for Regenerative Cures at UC Davis Health. Cells are known to be among the most promising cell types in regenerative medicine.

The lab is a Good Manufacturing Practices (GMP) lab for safe use in humans. This is where 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, a scientist at the Department of Surgery’s Center for Surgical Bioengineering, who leads the team that creates the stem cell patches and delivered to the operating room. . “The time we remove the cells, the time we sow on the scaffold and the time we deliver, are all critical.”

A first in medical history

During Emily’s landmark procedure, a 40-person operating and cell prep team performed the painstaking dance she had long been preparing for.

After Emily was placed under general anesthesia a small opening was made in her uterus and they floated the fetus to this incision point so they could expose her spine and the spina bifida defect . Surgeons used a microscope to carefully begin the repair.

Then the moment of truth: the stem cell patch was placed directly on the exposed spinal cord of the fetus. Fetal surgeons then closed the incision to allow the tissue to grow back.

“The placement of the stem cell patch went without a hitch. Both mother and fetus did very well!” said the farmer.

The team declared the surgery, the first of its kind, a success.

Delivery day

On September 20, 2021, at 35 weeks and five days gestation, Robbie was born 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 to me. I could see her toes wiggle for the first time. It was so reassuring and a bit out of this world,” Emilie said.

For Farmer, this day is what she had long hoped for, and it came with surprises. If Robbie was left untreated, she was expected to be born with paralysis of her legs.

“From birth it was very clear that she was kicking her legs and I very clearly remember saying, ‘Oh my God, I think she’s wiggling her toes!’ said Farmer, who noted that the sighting was not official confirmation. , but it was promising. “It was amazing. We kept saying, ‘Do I see this? Is this real?'”

Mom and baby are home and healthy. Robbie just celebrated his first birthday.

The CuRe team are cautious about drawing conclusions and say there is still a lot to learn 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 check at 30 months to see if they are walking and potty training.

“This experience was larger than life and exceeded all expectations. I hope this trial will improve the quality of life for so many patients to come,” said Emily. “We are honored to be part of history in the making.”

Video: https://youtu.be/TGvHRqsopQo

About Antoine L. Cassell

Check Also

IMU-838 treatment associated with low rate of confirmed disability worsening in relapsing MS

Recently reported interim data from the Phase 2 EMPhASIS trial (NCT03846219) of Immunic’s investigational agent, …