Neural tube defects are among the most challenging congenital conditions in medicine, with a devastating burden on patients, families, and health care systems. These defects arise when the neural tube, the embryonic structure that becomes the brain and spinal cord, fails to close properly during early fetal development. This failure can range in severity from minor disabilities to lethal malformations. Globally, nearly half a million babies are born each year with such defects. Spina bifida, one of the most recognized forms, continues to occur despite preventive measures such as folate supplementation. In the United States, annual hospital charges related to spina bifida were estimated at two billion dollars in 2024, underscoring the economic weight of lifelong multidisciplinary care for affected children.
Myelomeningocele is the most severe form of spina bifida. In this condition, the spinal cord and surrounding tissues remain exposed due to failure of closure, leading to leakage of cerebrospinal fluid. The developing spinal cord is then subjected to chemical damage from amniotic fluid and mechanical trauma from contact with the uterine wall. This dual insult results in a host of developmental abnormalities. Patients may suffer loss of motor function below the lesion level, causing paralysis, as well as bowel and bladder dysfunction. A common associated problem is hindbrain herniation, in which the lower portions of the brain — specifically the cerebellum and brainstem — are pulled downward from their normal position into the upper spinal canal. This can disrupt normal brain and spinal fluid flow, cause pressure on delicate brain structures, and lead to neurological symptoms.
The newly reported phase 1 trial explored a groundbreaking regenerative approach to myelomeningocele repair before birth — “Feasibility and safety of cellular therapy for in-utero repair of myelomeningocele (CuRe Trial): a first-in-human, phase 1, single-arm study.” The therapy uses placenta-derived mesenchymal stem cells, known as PMSCs, obtained from early-gestation placentas. These cells are uniquely suited for fetal applications due to their fetal origin, lack of tumor-forming potential, neuroprotective properties, and ability to reduce cell death (apoptosis). Importantly, when cultured in a specialized neurogenic medium, PMSCs adapt to secrete higher concentrations of neurotrophic growth factors and can rescue dying neurons in laboratory settings.
In this trial, PMSCs were seeded onto an FDA-approved extracellular matrix graft and placed directly onto the exposed fetal spinal cord during standard prenatal surgery for myelomeningocele. The aim was to augment the mechanical effects of surgical closure with a biologically active therapy capable of protecting and regenerating neural tissue during a crucial window of fetal neurodevelopment. Investigators designed the study to rigorously monitor surgical feasibility and early safety, given the unknowns of placing living allogeneic stem cells into the developing central nervous system.
The results are highly encouraging. All six patients in the initial cohort successfully received the therapy, and no stem cell-related adverse events were observed. Every newborn had reversal of hindbrain herniation on postnatal MRI, with intact and fully healed surgical repair sites. There was no evidence of abnormal tissue growth or tumor formation. The therapy did not interfere with the known benefits of fetal surgery, nor did it cause complications in wound healing. These findings suggest that PMSCs can be safely integrated into prenatal surgery without compromising established surgical gains.
This pioneering work also highlights the growing intersection between regenerative medicine and personalized medicine. Personalized medicine is not only about genetic diagnostics and targeted drugs, it increasingly encompasses designing and delivering the right biologic or regenerative therapy at the right developmental moment for maximum impact. In the case of myelomeningocele, early, targeted intervention with a biologically active repair tailored to the unique characteristics of the patient’s lesion could represent the next evolution in precision perinatal care.
The implications go beyond this single condition. This trial demonstrates a scalable and clinically feasible platform for delivering biologically active therapeutics directly to the fetus. By intervening early in development, such therapies may alter lifelong health trajectories, potentially preventing paralysis, preserving bladder and bowel function, and reducing the societal and economic impact of chronic disability. While longer-term follow-up is needed to confirm sustained benefits, this first-in-human study provides hope for addressing a serious unmet medical need for which no curative alternatives exist. It also adds to the very short list of regenerative medicine therapies reaching clinical application, particularly in the prenatal setting.
