In-Utero Stem Cell Therapy for Myelomeningocele Shows Early Safety and Feasibility: The Lancet
A first-in-human, phase I single-arm trial has found that in-utero treatment of myelomeningocele, the most severe form of spina bifida, using allogeneic live stem cells was both feasible and safe. All six infants in the study had an intact repair site at birth, with no cerebrospinal fluid leaks, infections, or abnormal tissue growth observed. Currently, there are no commercially available regenerative stem cell therapies approved for treating diseases in utero, making this study an important early step in advancing prenatal regenerative medicine. The study was published in the journal The Lancet by Prof. Diana F. and colleagues.
The Management of Myelomeningocele Study (MOMS) had already determined in its prior research that in-utero surgical correction of myelomeningocele reduces the need for the placement of a ventriculoperitoneal shunt and improves some neurological outcomes when compared with the traditional post-natal procedure. The present study is a phase 1, single-dose, single-arm trial of pregnant women who are carrying a fetus diagnosed with myelomeningocele and who are enrolled at the University of California, Davis School of Medicine in Sacramento, California. The study had a staggered enrollment design for safety reasons and is registered on ClinicalTrials.gov (NCT04652908).
The inclusion criteria for the study are gestational age between 19 and 26 weeks, an upper boundary of the myelomeningocele defect between thoracic level T1 and sacral level S1, hindbrain herniation on magnetic resonance imaging (MRI), and a normal fetal karyotype. Between June 21, 2021, and December 5, 2022, six women were enrolled in the trial. At the time of the procedure, the gestational age of the fetuses was between 24 weeks and 5 days and 25 weeks and 5 days.
Key findings:
In this phase 1 first-in-human study, six pregnant women with fetuses diagnosed with myelomeningoceles between 24+5 and 25+5 weeks of gestation received stem cell-augmented in-utero repair.
Infants were born at a median gestational age of 34+5 weeks, ranging from 33+2 to 36+6 weeks.
All infants had intact repair sites without cerebrospinal fluid leak, infection, abnormal tissue growth, or tumor formation. There were no cell-mediated adverse effects.
Based on the safety data it was determined that the therapy is safe enough to proceed with non-staggered enrollment of 35 patients with an expanded phase 1/2a clinical trial. This will be followed by further investigation of potential efficacy, including neurological and functional outcomes.
Should subsequent clinical trials verify improved outcomes with regard to motor and cognitive function, stem cell-augmented fetal repair could be considered a major breakthrough beyond the status quo established by the MOMS trial.
In this first-in-human study, it was found that prenatal myelomeningocele repair with allogeneic live placenta-derived mesenchymal stem cells is safe, with no cell-related adverse effects. These findings support further clinical trials with potential benefits for children with spina bifida with regard to neurological outcomes.
Reference:
Farmer, D. L., Kumar, P., Reynolds, E., Lee, S. Y., Powne, A. B., Pivetti, C. D., Zwienenberg, M., McLennan, A. S., Nolta, J. A., Brown, E. G., Saadai, P., Hirose, S., & Wang, A. (2026). Feasibility and safety of cellular therapy for in-utero repair of myelomeningocele (CuRe Trial): a first-in-human, phase 1, single-arm study. Lancet, 407(10531), 867–875. https://doi.org/10.1016/s0140-6736(25)02466-3
