Cryopreserved Human Umbilical Cord as a Meningeal Patch in Fetoscopic Spina Bifida Repair (HUC-FICS): Single Arm Phase III Trial - PROJECT SUMMARY Fetal intervention to repair spina bifida in utero has dramatically improved clinical outcomes for affected children, but they still face lifelong morbidity characterized by ongoing deficits in motor function. Spinal cord tethering (SCT) due to scar formation at the surgical site contributes to suboptimal motor outcomes and long-term neurological complications and may require multiple surgeries in later life. The conventional method for in-utero spina bifida repair—open hysterotomy with two-layer closure of the neural tube defect—may contribute to SCT, as it disrupts the arachnoid meningeal layer, a protective barrier that reduces the spinal cord’s exposure to inflammatory cells and fibroblasts involved in scar formation. In addition, open hysterotomy increases maternal risks, including risk of uterine rupture, and necessitates cesarean delivery. Novel treatment strategies are needed to minimize inflammation and scarring at the spina bifida repair site while decreasing maternal morbidities associated with hysterotomy. To address these needs, we have developed an innovative approach consisting of laparotomy-assisted fetoscopic (LAF) spina bifida repair using a cryopreserved human umbilical cord graft (HUC) as a meningeal patch placed between the spinal cord and skin layer. Our preclinical studies demonstrated that using HUC as a meningeal patch for spina bifida repair improved spinal cord function by reducing inflammation and SCT and by regenerating the arachnoid layer. Based on these findings, the FDA approved human studies of spina bifida repair with HUC using a minimally invasive LAF approach. We successfully completed the feasibility study in 50 patients, more than half of whom delivered vaginally, and the Single-Arm Phase III efficacy study is underway. This study aims to evaluate neurological, motor functional, and developmental outcomes, and their correlation with radiological assessments of SCT, in children undergoing LAF spina bifida repair with HUC patch. We hypothesize that LAF spina bifida repair with a HUC patch will improve 12- and 30-month clinical outcomes compared with conventional repair outcomes from the randomized Management of Myelomeningocele Study (MOMS). We will test this hypothesis via three specific aims. Aim 1 will compare neurological outcomes for children undergoing LAF spina bifida repair using HUC meningeal patch against outcomes after conventional prenatal repair at 12 and 30 months. Independent ambulation at 30 months is our primary outcome. Aim 2 will characterize anatomic changes at surgical repair sites using Magnetic Resonance Imaging (MRI) after LAF spina bifida repair and correlate with functional status. Pediatric neuroradiologists will quantify the tethering index to assess the degree of SCT. Aim 3 will evaluate standardized developmental outcomes at 30 months in children after LAF spina bifida repair. In collaboration with a developmental pediatrician, we will assess whether improvements in motor function translate to developmental improvements for these children. Successfully achieving these aims will assess LAF with HUC's efficacy and potentially establish it as a viable or superior treatment for spina bifida repair, improving outcomes for both mothers and children.
