Comment on “Feasibility and Safety of Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe Trial): A First-in-Human, Phase 1, Single-Arm Study”

Neural tube defects, including spina bifida, are a spectrum of congenital conditions that carry a significant worldwide disability burden. Spina bifida is present in one out of every 2800 US births. The most severe form of this anomaly, myelomeningocele, results from failed neural tube closure, leaving the fetal spinal cord vulnerable to chemical and mechanical injury in utero. The possible resulting morbidities are severe, including hindbrain herniation, hydrocephalus, and paralysis. While in utero repair improves outcomes compared with postnatal closure, it does not reverse existing spinal cord damage, and many patients still cannot ambulate. One avenue of research that shows promise in preclinical studies is in utero treatment with placenta-derived mesenchymal stem cells (PMSCs), which have neuroprotective, anti-apoptotic, and anti-inflammatory properties. The phase 1 CuRe Trial evaluated the feasibility and safety of PMSC treatment when applied on an extracellular matrix scaffold during in utero repair of myelomeningocele.

This first-in-human, single-arm study included eligible patients at 19 to 26 weeks’ gestation with fetal myelomeningocele or myeloschisis from T1 to S1, hindbrain herniation on MRI, and normal karyotype. Donated placentas were used to generate cell lines, which were expanded, cryopreserved, tested, and seeded onto an FDA-approved dural graft before surgery. The investigational product was applied directly to the exposed fetal spinal cord during standard open fetal repair, followed by routine closure and weekly ultrasound monitoring until delivery. Primary outcomes were the feasibility of product application and safety, defined by the absence of cerebrospinal fluid leak, infection, wound-healing failure, tumor formation, or death during birth hospitalization. Due to the investigatory nature of this study, treatment was staggered to allow for the attainment of safety outcomes between patients.

Six pregnant patients were enrolled between June 2021 and December 2022. All fetuses had myelomeningocele or myeloschisis diagnosed in the second trimester, lesion levels from L1 to S1, and hindbrain herniation confirmed on MRI. Surgery occurred between 24+5 and 25+5 weeks’ gestation, and the PMSC-ECM product was successfully applied in all cases without technical, maternal, fetal, or intraoperative complications requiring transfusion, resuscitation, or emergent delivery. Newborns were delivered by cesarean at a median gestational age of 34+5 weeks. Two infants were delivered before 34 weeks, one of which required intubation due to transient respiratory distress syndrome attributed to prematurity. At birth, all repair sites were intact, with no cerebrospinal fluid leak, infection, wound separation, or tumor growth. Postnatal MRI showed reversal of hindbrain herniation and no abnormal tissue proliferation, and no infants required shunt placement for hydrocephalus before discharge.

This trial demonstrates the early safety and clinical feasibility of PMSC-ECM for in utero treatment of myelomeningocele. While fetal stem cell therapy remains limited to early-phase trials, this study adds to emerging safety data from in utero cell-based therapies for conditions like thalassemia and osteogenesis imperfecta. However, the study was limited by its small sample size and focus on birth hospitalization outcomes rather than long-term neurologic function. These results were sufficient for continuation of the trial, with follow-up planned through age 6 years to assess safety, motor function, bowel and bladder function, and preliminary efficacy.

(Summarized from Farmer DL, Kumar P, Reynolds E, et al. Feasibility and safety of cellular therapy for in utero repair of myelomeningocele (CuRe Trial): a first-in-human, phase 1, single-arm study. Lancet. 2026;407:867–875. doi:10.1016/S0140-6736(25)02466-3).