By D. Maan, Jadetimes News
Prenatal care could be revolutionised by the implementation of innovative medicines for foetuses with neurological abnormalities
Michelle Johnson’s fourth pregnancy was proceeding as expected until the specialist conducting her 20 week ultrasound showed signs of unease. The ultrasonographer became noticeably awkward, asking unusual questions like whether they already had children. Days later, the department’s chief radiologist called with a solemn tone, informing her that her child had spina bifida and urgently needed to see a specialist in gestational fetal medicine. Spina bifida, scientifically known as myelomeningocele, occurs when the spinal cord, initially forming as a tube that folds to encase the nervous system, fails to fully close.
This results in nerves protruding through a small bulge along the spine. This congenital defect can lead to lifelong cognitive issues, impaired mobility, and paralysis from the waist down. "It was devastating," recalls Johnson, then 35 and living in Portland, Oregon, USA. "I was in complete shock." Approximately 1,400 babies are born with spina bifida in the US each year. The exact cause of this complex condition remains unknown, though it is believed to involve a combination of genetic and environmental factors. Factors such as inadequate folic acid intake during pregnancy or specific anti seizure medications have been linked to a higher risk, but their precise role is unclear.
Spina bifida is commonly managed within 24 to 48 hours after delivery: surgeons perform a procedure to seal the spinal cord and reposition it inside the infant's body in order to prevent additional harm. During the process of arranging meetings with medical experts, Johnson was notified by a nurse about a novel initiative in California that employs stem cells to address spina bifida in foetuses. Choosing to participate meant that her kid would be the second human patient to get this treatment. Johnson perceived it as an irresistible opportunity. She described the procedure, which must be done before the 26th week of pregnancy, as a time sensitive endeavour. Following multiple scans, blood tests, and interviews, she commenced on this remarkable expedition.
It feels like we've just hit the jackpot ''Michelle Johnson''
In recent decades, there have been substantial advancements in prenatal screening for neurological diseases. Advancements in technologies such as genetic analysis, neuroimaging, and high resolution foetal magnetic resonance imaging (MRI) have empowered doctors to study the neurological systems of developing foetuses and identify potential life altering diseases at an earlier stage and with greater frequency. Nevertheless, despite these technological progressions, physicians have been constrained in their choices for managing these illnesses until the time of delivery. A significant proportion of crucial brain development takes place prior to a child's birth.
Currently, a fresh surge of innovative in utero neuroscience treatments is begun to alter this situation. Multiple pioneering trials are currently in progress, evaluating both surgical and medicinal interventions that allow doctors to reverse abnormalities in infants before to their birth. Jeffrey Russ, a paediatric neurologist at Duke University, recently stated in an academic piece that the area of therapy is on the brink of a new age, with in utero treatment being dubbed as the "next frontier" in neurology.
An example of such pioneering interventions is the initial clinical trial sanctioned by the FDA, which aims to treat spina bifida prenatally by employing placental stem cells. The CuRe Trial, led by foetal surgeon Diana Lee Farmer from the University of California, Davis, is the culmination of 25 years of research and development. According to Farmer's extensive study, in utero procedures, which include sewing shut the opening in the spinal cord, have become the standard treatment for severe cases of spina bifida. These surgeries are performed during pregnancy and are more effective in slowing down the progression of the condition and improving patient outcomes compared to surgeries performed after delivery. Nevertheless, her latest endeavour strives to surpass previous achievements. By using a patch containing stem cells from the mother's placenta, specifically "mesenchymal stromal cells," and carefully culturing them over a four day period, it is anticipated that the repair of the open neural tube can reverse the existing damage at the time of diagnosis.
Aijun Wang, the bioengineer responsible for the development of this stem cell technology for the CuRe trial, describes these stem cells as highly intelligent. "They have the ability to safeguard neurons from environmental induced cell death." Initial evidence from trials conducted on lambs with spina bifida indicated that the treatment enabled them to ambulate without any discernible impairment, when they would have otherwise experienced paralysis in their hind limbs. Comparable outcomes were noted when the procedure was executed on bulldogs.
More than 30 people were present when Johnson, just shy of 26 weeks pregnant, became the second patient to undergo this pioneering surgery. An incision was made in her belly, the uterus was partially extracted, and the fetus was positioned to access the spinal hernia. Using microscopes, doctors applied the stem cell patch to the tiny spine. Without treatment, her son Tobias would have been born paralyzed from the hips down. Instead, on February 1, 2022, he was delivered via C section, legs kicking and toes wriggling. "It just feels like we won the lottery," Johnson said.
Tobias will be monitored until he is 30 months old to assess the procedure's safety and efficacy, with likely follow ups until age five. To date, 10 more patients have received CuRe treatment, and Farmer's team has secured $15 million for 29 additional patients, aiming to enroll about 10 per year. By 2028, they hope to determine if this therapy could become standard for children nationwide.
"I'm hopeful we can significantly improve outcomes for kids with spina bifida," says Farmer. "But like every good scientific project, answering one question opens the door to another."
According to Russ, this is cutting edge science for surgically reparable anatomic conditions. However, another frontier for in utero therapies lies in addressing neurological conditions at a molecular or genetic level. This is a "totally new concept" that will "open a whole new realm," says Russ.
At Duke University, his colleagues helped design the protocol for the first ever in utero treatment for Pompe disease a rare genetic disorder causing cells to accumulate excessive complex sugars. This leads to neurological issues, breathing problems, heart complications, and muscle weakness, with most patients dying within one or two years of birth.