Stem Cell Therapy for Spina Bifida

(CuRe Trial)

Overseen By Maria G Hernandez, CPT1

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, Davis

Disqualifiers: Multifetal pregnancy, Diabetes, Obesity, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for spina bifida, a birth defect that can cause paralysis and issues with walking and bladder and bowel control. The researchers add stem cells from the placenta to the surgery typically performed before birth to enhance walking abilities and protect the spinal cord. This method is known as Cellular Therapy, also called the CuRe Trial or Cellular Therapy for In Utero Repair of Myelomeningocele. The trial includes two groups: one receiving stem cells during surgery and another undergoing standard treatment without them. It seeks pregnant women diagnosed with a fetus having spina bifida who meet specific criteria for fetal surgery. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using special cells from the placenta, called placental mesenchymal stromal cells (PMSC), along with a supportive structure, appears promising for safety in humans. Studies have focused on applying these cells directly to the fetal spinal cord. So far, no unusual tissue growth or leftover cells appeared three months after the procedure, suggesting the treatment could be safe for humans.

Animal studies also support these findings. They have demonstrated that these cells can improve movement and assist with bowel and bladder function without causing harm. While these results are encouraging, it is important to remember that this trial remains in the early stages. Some safety information is available, but more data is needed to fully understand the treatment's effects in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using PMSC-ECM for spina bifida because it introduces a novel approach to treating this condition. Unlike traditional surgical repairs, which primarily focus on closing the defect after birth, PMSC-ECM is administered during fetal surgery, potentially promoting better spinal healing and reducing long-term complications. This treatment leverages the regenerative properties of placental stem cells, aiming to improve outcomes by enhancing tissue repair and nerve protection, which could be a game-changer for managing spina bifida from early on.

What evidence suggests that this trial's treatments could be effective for spina bifida?

Research has shown that adding placental stem cells during spina bifida surgery might improve walking ability. In animal studies, these cells significantly improved walking and bladder function when used in spina bifida repair. The living cells appear to protect and possibly heal spinal cord damage. This trial will test the one-time administration of PMSC-ECM during in utero fetal myelomeningocele surgery. Although research in humans remains in the early stages, promising results from animal studies offer hope for better outcomes. ^{1 6 7 8 9}

Who Is on the Research Team?

Diana L Farmer, MD

Principal Investigator

UC Davis School of Medicine

Are You a Good Fit for This Trial?

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

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.

Your chromosomes are normal, or if you are pregnant, certain test results are acceptable.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cellular Therapy

Trial Overview 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.

How Is the Trial Designed?

Group I: non-PMSC untreated contemporaneous cohort Experimental Treatment 1 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-ECM Experimental Treatment 1 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

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Diana Lee Farmer

Lead Sponsor

Trials

1

Recruited

60+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Published Research Related to This Trial

In a study involving 25 fetal lambs with spina bifida, the delivery of neural stem cells (NSCs) alongside standard surgical repair significantly improved survival rates and reduced major paraparesis compared to no repair.

The NSCs successfully engrafted in the damaged spinal cord areas, remained undifferentiated, and produced neurotrophic factors, suggesting their potential as a therapeutic strategy for spina bifida without worsening the condition of the animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery for spina bifida. Fauza, DO., Jennings, RW., Teng, YD., et al.[2022]

In a study involving 29 pregnant dams and 100 fetuses with induced spina bifida, both placental-derived (pMSCs) and amniotic fluid-derived mesenchymal stem cells (afMSCs) showed significantly higher rates of defect coverage compared to saline and untreated groups, indicating their efficacy in treating spina bifida.

There was no significant difference in the effectiveness of pMSCs and afMSCs, suggesting that either cell type can be used for transamniotic stem cell therapy (TRASCET) in prenatal management of spina bifida, providing flexibility in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison between placental and amniotic mesenchymal stem cells for transamniotic stem cell therapy (TRASCET) in experimental spina bifida. Feng, C., D Graham, C., Connors, JP., et al.[2018]

In a study involving 54 immunodeficient mice, the implantation of placental mesenchymal stromal cells (PMSC) seeded on a dural extracellular matrix (ECM) showed no signs of tumor formation after 4 weeks and 6 months, indicating a strong safety profile for this treatment.

No human DNA was detected in the mice, suggesting that the PMSC did not persist in the host, which further supports the safety of using PMSC-ECM in future clinical trials for treating myelomeningocele.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placental Mesenchymal Stromal Cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair. Jackson, JE., Pivetti, C., Stokes, SC., et al.[2022]

Using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) in conjunction with in utero surgical repair of myelomeningocele (MMC) significantly improved neurologic function in a fetal lamb model, with 67% of treated lambs able to walk independently compared to none in the control group.

PMSCs not only enhanced motor function but also preserved spinal cord neuron density, suggesting their potential as a promising therapy for improving outcomes in children with MMC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placental mesenchymal stromal cells rescue ambulation in ovine myelomeningocele. Wang, A., Brown, EG., Lankford, L., et al.[2019]

Induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) were successfully derived from skin fibroblasts of three newborns with spina bifida aperta (SBa), indicating a potential source for future therapeutic applications.

The generated iPSCs exhibited characteristics of human pluripotent stem cells and were differentiated into NSPCs, which could be expanded for potential use in treating neurological and urological defects associated with SBa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta. Bamba, Y., Nonaka, M., Sasaki, N., et al.[2022]

In this study, placental mesenchymal stromal cells (PMSCs) from all gestational ages (first, second, and term) were found to secrete neuroprotective factors, indicating their potential for improving motor outcomes in children with myelomeningocele after in utero repair.

The research showed that certain cell lines from each trimester exhibited significant neuroprotective capabilities, suggesting that a wider range of PMSCs could be used in clinical applications to enhance treatment outcomes for affected children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells. Stokes, SC., Kabagambe, SK., Lee, CJ., et al.[2023]

In a study involving 20 pregnant Lewis dams and their fetuses with induced spina bifida, intra-amniotic injection of amniotic-derived neural stem cells (aNSCs) resulted in successful localization of donor cells in 93.3% of the affected fetuses.

The injected aNSCs were found to cluster in the neural placode and retained an undifferentiated state, suggesting that intra-amniotic delivery could be a viable method for enhancing spinal cord repair in spina bifida.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-amniotic delivery of amniotic-derived neural stem cells in a syngeneic model of spina bifida. Turner, CG., Pennington, EC., Gray, FL., et al.[2013]

Transamniotic stem cell therapy (TRASCET) using amniotic fluid-derived mesenchymal stem cells (MSCs) can promote coverage of spina bifida defects in a fetal model, indicating potential for prenatal treatment.

The successful coverage is linked to significant downregulation of specific growth factors (Egf, Fgf-2, Tgfb-1) and immune markers (CD45) in both the defect area and fetal bone marrow, suggesting a complex host response that enhances MSC activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Mechanistic Screening of Transamniotic Stem Cell Therapy in the Rodent Model of Spina Bifida: Host Bone Marrow and Paracrine Activity. Lazow, SP., Tracy, SA., Chalphin, AV., et al.[2021]

The study involved 11 children with spina bifida who received autologous bone marrow mononuclear cell (BMMNC) infusions, showing no severe adverse events, indicating the procedure's safety.

After two BMMNC infusions, significant improvements were observed in bowel and bladder function, with a reduction in the need for assistance with stool expulsion and urine leakage, as well as an increase in bladder capacity and independent walking ability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of autologous bone marrow mononuclear cell administration in the treatment of neurologic sequelae in children with spina bifida. Nguyen, LT., Le, HT., Nguyen, KT., et al.[2023]

In a study using Sprague-Dawley rats with induced spina bifida, cryopreserved human umbilical cord (HUC) patches significantly promoted the migration of native cells and showed minimal inflammatory response compared to biocellulose film (BCF) patches.

HUC patches demonstrated effective cellular migration of epithelial, astrocyte, and endothelial cells, suggesting that HUC may be a superior material for prenatal spina bifida repair due to its regenerative properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreserved human umbilical cord versus biocellulose film for prenatal spina bifida repair in a physiologic rat model. Snowise, S., Mann, L., Morales, Y., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34217509/

Efficacy of clinical-grade human placental mesenchymal ... Conclusions: Clinical-grade placental mesenchymal stromal cells seeded on an extracellular matrix rescued ambulation in a fetal ovine myelomeningocele model.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9365330/

Placental Mesenchymal Stromal Cells: Preclinical Safety ... We developed clinical-grade Placental Mesenchymal Stromal Cells seeded on a dural Extracellular Matrix (PMSC-ECM), which have been shown to improve motor ...

3. cirm.ca.gov cirm.ca.gov/our-progress/awards/placental-stem-cells-utero-treatment-spina-bifida/

Placental Stem Cells for the In Utero Treatment of Spina Bifida J Pediatr Surg (2017): Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324925001884

A Placental Mesenchymal Stromal Cell Living Therapeutic ... In the randomized MOMS trial, that compared in utero and post-natal closure of the spinal cord defect, 54% of the patients walked in the in utero closure group ...

5. journals.lww.com journals.lww.com/neurosurgery/fulltext/2022/04001/184_placental_mesenchymal_stromal_cells_seeded_on.94.aspx

184 Placental Mesenchymal Stromal Cells Seeded on an... We have shown placental mesenchymal stromal cells (PMSCs) applied in utero improve ambulatory function and preserve motor neurons in an ovine model of spina ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9415987/

Long-term Safety Evaluation of Placental Mesenchymal ... This study evaluated the safety of PMSC-ECM application directly onto the fetal spinal cord in preparation for a clinical trial.

7. jpedsurg.org jpedsurg.org/article/S0022-3468(21)00640-0/abstract

Long-term safety evaluation of placental mesenchymal ... There was no evidence of abnormal tissue growth or PMSC persistence at three months following in utero application of PMSC-ECM to the spinal ...

8. cirm.ca.gov cirm.ca.gov/about-cirm/publications/placental-mesenchymal-stromal-cells-preclinical-safety-evaluation-fetal-myelomeningocele-repair/

Preclinical Safety Evaluation for Fetal Myelomeningocele ... We developed clinical-grade placental mesenchymal stromal cells seeded on a dural extracellular matrix (PMSC-ECM), which have been shown to improve motor ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022346821004358

Efficacy of clinical-grade human placental mesenchymal ... Conclusions. Clinical-grade placental mesenchymal stromal cells seeded on an extracellular matrix rescued ambulation in a fetal ovine myelomeningocele model.