Could a simple injection fix spina bifida before birth?

spina bifida myelomeningocele
Prenatal cell therapy could avoid the need for invasive surgery to repair myelomeningocele.

The neural tube, which becomes the spinal cord and brain, is supposed to close during the first month of prenatal development. In children with spina bifida, it doesn’t close completely, leaving the nerves of the spinal cord exposed and subject to damage. The most common and serious form of spina bifida, myelomeningocele, sets a child up for lifelong disability, causing complications such as hydrocephalus, leg paralysis, and loss of bladder and bowel control.

New research from Boston Children’s Hospital, though still in animal models, suggests that standard amniocentesis, followed by one or more injections of cells into the womb, could be enough to at least partially repair spina bifida prenatally.

Currently, the standard procedure is to operate on infants soon after delivery. In an effort to minimize nerve damage—caused as the fetus moves around or by chemical injury from the amniotic fluid itself—the Management of Myelomeningocele Study (MOMS) tested fetal surgery to cover over the malformation with commercially available acellular skin or artificial materials.

While MOMS showed improved outcomes, leading patient randomization to be stopped in 2011, opening the mother’s uterus carries major risks, including preterm labor. Fetal surgery cannot be done safely until the 19th to 25th week of pregnancy, when much of the nerve damage has already occurred, and not everyone is eligible; sometimes the surgery is too risky for the mother, or the defect is too small or too large to justify it. Of more than 1,000 expectant mothers screened for the MOMS study, only 183 were enrolled.

Transamniotic stem cell therapy

Amniotic mesenchymal stem cells for spina bifida
Amniotic mesenchymal stem cells can be multiplied rapidly in the lab.

That’s where surgeon and tissue engineering pioneer Dario Fauza, MD, PhD, comes in. He has conducted more than a decade of testing in a series of animal models showing that amniotic fluid, commonly drawn from expectant mothers by amniocentesis, particularly when the developing baby has an anomaly such as spina bifida, contains a unique population of mesenchymal stem cells. Fauza and colleagues have shown that these cells, present throughout pregnancy, naturally find their way to fetal injuries in utero and repair them. And they can be expanded rapidly in a laboratory dish.

“Even though I am a surgeon, the idea of harnessing natural healing non-surgically is very appealing,” says Fauza.

In the new study, reported in May at the American Pediatric Surgical Association annual meeting, Fauza, with his research fellow Beatrice Dionigi, MD, and other colleagues, showed that these stem cells, expanded in the lab and injected back into the womb in large numbers, caused skin to grow over the spinal cord in a rat model, sometimes completely covering the defect.

Harnessing natural repair mechanisms

This method—which Fauza calls Transamniotic Stem Cell Therapy, or TRASCET—will of course require more testing before it can be tried in humans, but it has the potential to be a safe and very practical option to prevent more damage to the spinal cord.

Dario Fauza, MD, PhD“The problem with surgical closure is that you can only do it relatively late in the pregnancy,” says Fauza. “We found out that you may not need to operate: If you inject cells in large enough amounts, they will trigger coverage of the defect, at least in this animal model. And you can potentially inject these cells very early in pregnancy—as much as 10 to 12 weeks earlier than in the MOMS study—and offer the treatment to many more patients.”

Over the years, Fauza has repeatedly put amniotic mesenchymal stem cells through their paces, demonstrating the ability to expand them in the lab in conformance with FDA Good Manufacturing Practice (GMP).

He hopes to get FDA approval for using the cells to make a tissue-engineered patch for babies with a common birth defect known as congenital diaphragmatic hernia, in this case implanting the patch after birth. His lab has also used these mesenchymal stem cells to grow segments of trachea and successfully grafted the tissue before birth in a large animal model.

While implanting engineered tissues such as these entails many FDA regulatory requirements, the requirements are fewer for simple cell injections from an autologous source (the fetus itself), and some—like meeting GMP requirements—have already been met.

“Our next hurdle is fine-tuning the technique in a large animal model and demonstrating functional benefits in the mid- to long-term,” says Fauza. “We also need to determine the best dose and administration regimen. But from the MOMS trial, we know that every time you cover the defect earlier, the child does better clinically.”

Next week, Vector looks at the broader arena of non-amniotic mesenchymal stem cell transplants. For more on care of spina bifida at Boston Children’s, visit the Spina Bifida Center or follow the Center on Facebook.