Diana Farmer, M.D., and Shinjiro Hirose, M.D., during Emily's surgery. Credit: UC Davis Health.
If Robbie, who just celebrated her first birthday on Sept. 20, is anything to go by, a clinical trial for the world’s first stem cell treatment for spina bifida delivered during fetal surgery is off to an incredibly successful start.
Spina bifida, also known as myelomeningocele, occurs when spinal tissue fails to fuse properly during the early stages of pregnancy, leading 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.
Robbie was the first of three babies thus far to receive groundbreaking fetal surgery to reverse the paralysis and other abnormal functions caused by spina bifida before birth. Thirty-two other babies will be treated as part of the ongoing CuRe Trial (Cellular Therapy for In Utero Repair of Myelomeningocele).
The CuRe Trial is the result of 25 years of research by Diana Farmer, the world’s first woman fetal surgeon, and professor and chair of surgery at UC Davis Health.
A quarter of a century
Working on the Management of Myelomeningocele Study clinical trial in the early 2000s, Farmer was part of a team that showed fetal surgery reduced neurological deficits from spina bifida. Many children in that study showed improvement but still required wheelchairs or leg braces.
Over the next couple decades, Farmer worked with colleagues at UC Davis to find ways to use stem cells and bioengineering to advance surgical effectiveness and improve outcomes, even launching multiple treatment centers during that time.
A huge breakthrough came when Farmer and her team showed 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.
Then, with slight revisions, the team did it again for a pair of English bulldogs named Darla and Spanky. They became the world’s first dogs to be successfully treated with surgery and stem cells to improve their mobility with naturally occurring spina bifida. By their post-surgery re-check at 4 months old, Darla and Spanky were able to walk, run and play.
Human trial
With successes in animals, CuRe was approved as the world’s first human trial for stem cell treatment of spina bifida delivered during fetal surgery in Spring 2021.
Farmer team manufactures mesenchymal stem cells from placental tissue in the UC Davis Health’s Institute for Regenerative Cures. It was there scientists made the stem cell patch for their first human patients, mom-to-be Emily and her developing child that had been diagnosed with spina bifida.
“It’s a four-day process to make the stem cell patch,” said Priya Kumar, a 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.”
On July 12, 2021, at 25 weeks and five days gestation, Emily was placed under general anesthetic and wheeled into an operating room occupied by a 40-person team.
First, surgeons made a small opening in Emily’s uterus, then floated the fetus up to that incision point so they could expose the fetus’s spine and the spina bifida defect. Then, the carefully constructed stem cell patch was placed directly over the fetus’s exposed spinal cord. Finally, the fetal surgeons closed the incision to allow the tissue to regenerate.
The placement of the patch was a success, but Farmer and team still had to wait 3 months to see if the procedure worked.
When baby Robbie came out of the womb on Sept. 20, 2021, kicking her legs and wiggling her toes, the team was amazed. If Robbie had remained untreated, she was expected to be born with leg paralysis.
“We kept saying, ‘Am I seeing that? Is that real?’” said Farmer.
Since then, two more babies have received the fetal surgery and similarly been born healthy and with the ability to control their legs, feet and toes. All three babies—and any others born in the future—will be monitored by Farmer and her team until they are 6 years old, with a key checkup happening at 30 months to see if they are walking and potty training. The CuRe trial was approved for a total of 35 patients.
“The first part of this trial is about safety,” said Farmer. “We’re just making sure there are no unexpected things. Having stem cells in the spinal cord of a fetus is brand new. We are cautiously optimistic.”