Stem Cell Therapy for Spina Bifida
(CuRe Trial)
Recruiting in Palo Alto (17 mi)
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: University of California, Davis
Disqualifiers: Multifetal pregnancy, Diabetes, Obesity, Hypertension, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?Spina bifida, or myelomeningocele (MMC), is a birth defect that results in paralysis, excess fluid on the brain (hydrocephalus), and impaired ability to urinate and have bowel movements normally. In a previous study (the MOMS trial), surgery before birth (in-utero/fetal surgery) was shown to reduce the need for shunting for hydrocephalus. There was also some improvement in ambulation, but 58 % of the children still could not walk unassisted.
This study is testing living stem cells from placenta added to the fetal repair in an effort to improve the ability to walk. Previous animal studies have shown dramatic improvement in walking and bowel and bladder function when placental stem cells are added to MMC repair. Use of these "living" cells may protect the developing spinal cord, prevent further injury, and may even reverse existing damage to the nerves that control movement. This study is assessing the safety and efficacy of adding stem cells to open fetal surgery for MMC in humans.
Do I need to stop my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment for spina bifida?
Research shows that using placenta-derived mesenchymal stromal cells (PMSCs) during in utero repair of spina bifida in animal models significantly improves motor function at birth. This suggests that adding these cells to the treatment could enhance outcomes for patients with spina bifida.
12345Is stem cell therapy for spina bifida safe for humans?
Preclinical studies using placental mesenchymal stromal cells (a type of stem cell) for spina bifida repair have shown promising safety results in animal models, suggesting potential safety for future human trials.
35678How is the Cellular Therapy treatment for spina bifida different from other treatments?
This treatment is unique because it involves delivering stem cells to the fetus before birth to help repair the spinal cord, potentially improving neurological outcomes more effectively than traditional surgical methods alone.
145910Eligibility Criteria
This trial is for pregnant women over 18 with a fetus diagnosed with myelomeningocele, confirmed by ultrasound and MRI. The gestational age must be between 19-25 weeks, and the fetus should have a normal karyotype. Women can't join if they have certain conditions like incompetent cervix, placenta issues, positive HIV/Hepatitis-B status or other medical conditions that increase surgery risks.Inclusion Criteria
I am 18 years old or older.
You have a certain type of spinal defect and brain herniation that can be confirmed by ultrasound and MRI at a specific medical center.
You are in the 19th to 25th week of pregnancy, based on clinical information and first ultrasound evaluation.
+1 more
Exclusion Criteria
You are not eligible for fetal surgery, including if you are pregnant with more than one baby.
My unborn baby has a condition unrelated to spinal defects.
I cannot travel or follow the required check-ups for fetal surgery.
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
One-time administration of PMSC-ECM during in utero fetal myelomeningocele surgery
Immediate
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments at birth and up to 30 months
30 months
Participant Groups
The CuRe Trial tests the safety and effectiveness of adding stem cells to prenatal surgery for fetal spina bifida repair. It compares outcomes in fetuses treated with stem cells on a dural graft matrix versus an untreated group to see if there's improved mobility and development.
2Treatment groups
Experimental Treatment
Group I: non-PMSC untreated contemporaneous cohortExperimental Treatment1 Intervention
Contemporaneous cohort of patients undergoing routine fetal or postnatal MMC repair without PMSC-ECM (non-PMSC untreated contemporaneous cohort).
Group II: Treatment with PMSC-ECMExperimental Treatment1 Intervention
One-time administration of PMSC-ECM during the course of in utero fetal myelomeningocele surgery will be administered
Cellular Therapy is already approved in United States for the following indications:
🇺🇸 Approved in United States as CuRe Trial for:
- Spina bifida
- Myelomeningocele
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UC Davis HealthSacramento, CA
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Who Is Running the Clinical Trial?
University of California, DavisLead Sponsor
Diana Lee FarmerLead Sponsor
California Institute for Regenerative Medicine (CIRM)Collaborator
References
Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery for spina bifida. [2022]We introduce the notion of prenatal neural stem cell (NSC) delivery to the spinal cord as an adjuvant to fetal repair of spina bifida.
Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta. [2022]We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods.
Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells. [2023]The Management of Myelomeningocele Study demonstrated that in utero repair of myelomeningocele improved motor outcomes compared with postnatal repair. However, even after in utero repair, many children were still unable to walk. We have previously demonstrated that augmentation of in utero repair with early-gestation placental mesenchymal stromal cells (PMSCs) improves motor outcomes in lambs compared with standard in utero repair. The neuroprotective potential of PMSCs of all gestational ages has not been evaluated previously.
Intra-amniotic delivery of amniotic-derived neural stem cells in a syngeneic model of spina bifida. [2013]Neural stem cells (NSCs) may promote spinal cord repair in fetuses with experimental spina bifida. We sought to determine the fate of amniotic-derived NSCs (aNSCs) after simple intra-amniotic injection in a syngeneic model of spina bifida.
Placental mesenchymal stromal cells rescue ambulation in ovine myelomeningocele. [2019]Myelomeningocele (MMC)-commonly known as spina bifida-is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients.
Outcomes of autologous bone marrow mononuclear cell administration in the treatment of neurologic sequelae in children with spina bifida. [2023]To evaluate the safety and efficacy of autologous bone marrow mononuclear cell (BMMNC) infusion in the management of neurological sequelae in children with spina bifida (SB).
Placental Mesenchymal Stromal Cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair. [2022]Myelomeningocele (MMC) is the congenital failure of neural tube closure in utero, for which the standard of care is prenatal surgical repair. We developed clinical-grade placental mesenchymal stromal cells seeded on a dural extracellular matrix (PMSC-ECM), which have been shown to improve motor outcomes in preclinical ovine models. To evaluate the long-term safety of this product prior to use in a clinical trial, we conducted safety testing in a murine model.
Cryopreserved human umbilical cord versus biocellulose film for prenatal spina bifida repair in a physiologic rat model. [2019]Prenatal spina bifida (SB) repair with a regenerative patch may improve neurological outcomes by decreasing inflammatory scarring.
Initial Mechanistic Screening of Transamniotic Stem Cell Therapy in the Rodent Model of Spina Bifida: Host Bone Marrow and Paracrine Activity. [2021]Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can induce spina bifida coverage with neoskin. We initiated a mechanistic analysis of this host response.
A comparison between placental and amniotic mesenchymal stem cells for transamniotic stem cell therapy (TRASCET) in experimental spina bifida. [2018]We compared placental-derived and amniotic fluid-derived mesenchymal stem cells (pMSCs and afMSCs, respectively) in transamniotic stem cell therapy (TRASCET) for experimental spina bifida.