Feasibility and safety of cellular therapy for in-utero repair of myelomeningocele (CuRe Trial): a first-in-human, phase 1, single-arm study.

The Management of Myelomeningocele Study (MOMS) showed that repairing Myelomeningocele before birth can improve health outcomes for babies. Myelomeningocele is a severe type of Spina Bifida, a condition where the spine and spinal cord do not form correctly during development. In the MOMS study, surgeons repaired the spinal defect while the baby was still in the womb. This treatment lowered the number of babies who later needed a Ventriculoperitoneal Shunt, a device that drains excess fluid from the brain. Although surgery before birth helped improve movement in some children, more than half of the patients still could not walk on their own. Because of this, researchers began looking for ways to make the treatment more effective and improve nerve recovery. One possible solution involves using Placenta-Derived Mesenchymal Stem Cells (PMSCs). These stem cells come from the placenta and may help repair damaged nerve tissue. In earlier animal studies using fetal sheep with spina bifida, researchers placed these stem cells on a biological support material called an extracellular matrix. The treatment showed promising results, improving nerve function in the animals. Based on these findings, scientists wanted to test whether the treatment would be safe in humans. To study this, researchers conducted a phase 1 clinical trial at the University of California, Davis School of Medicine in Sacramento, California. Pregnant women were eligible for the study if their babies were diagnosed with spina bifida and met certain medical requirements. These included a pregnancy between 19 and 26 weeks, a spinal defect between the T1 and S1, signs in the spine, hindbrain herniation on MRI scans, and normal chromosome results. During surgery, doctors repaired the baby’s spinal defect while the fetus was still in the womb. They also applied a single dose of stem cells placed on a surgical patch called the Cook Biodesign Dural Graft. The stem cells were collected from donated placentas at UC Davis Medical Center from patients who gave permission. Before the surgery, the cells were tested to make sure they were safe, clean, and alive. The main goal of the phase 1 portion of the study was to check for safety problems. Researchers watched for poor healing, leakage of cerebrospinal fluid, infection, or abnormal tissue growth such as tumors. Six pregnant women joined the study between June 2021 and December 2022. The babies were delivered by cesarean section at about 35 weeks of pregnancy on average. At birth, all infants had fully healed repair sites with no fluid leaks, infections, or unusual tissue growth. MRI scans also showed that the hindbrain herniation had improved after treatment, and there were no signs of tumor formation. Researchers also found no negative side effects related to the stem cells. Because the treatment appeared safe, the researchers concluded that it is reasonable to continue studying this therapy. A larger clinical trial with more patients will be conducted to further test how safe and effective this stem-cell treatment may be.