Placental Mesenchymal Stem Cell Augmentation of Fetal Myelomeningocele Repair
Grant Award Details
Grant Type:
Grant Number:
CLIN1-11404
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$5,615,207
Status:
Closed
Progress Reports
Reporting Period:
Operational Milestone #5 (final)
Grant Application Details
Application Title:
Placental Mesenchymal Stem Cell Augmentation of Fetal Myelomeningocele Repair
Public Abstract:
Therapeutic Candidate or Device
Allogeneic Placenta-derived Mesenchymal Stem Cells Seeded on Cook Biodesign® Dural Graft Extracellular Matrix (PMSC-ECM)
Indication
Myelomeningocele (MMC) -or Spina Bifida -diagnosed prenataly
Therapeutic Mechanism
Placenta-derived mesenchymal stem cells (PMSCs) act by a paracrine mechanism, secreting a variety of growth factors, cytokines, and extracellular vesicles. This secretory profile is unique to PMSCs and is responsible for protecting motor neurons from apoptosis, which occurs due to chemical and mechanical trauma when motor neurons are exposed to the intrauterine environment. PMSC treatment increases the density of motor neurons in the spinal cord, leading to improved motor function.
Unmet Medical Need
The current standard of care in utero surgery, while promising, still leaves 58% of patients unable to walk independently. There is an extraordinary need for a therapy that prevents or lessens the severity of the devastating and costly lifelong disabilities associated with the disease.
Project Objective
IND filing, Phase 1/2 trial start-up activities
Major Proposed Activities
Allogeneic Placenta-derived Mesenchymal Stem Cells Seeded on Cook Biodesign® Dural Graft Extracellular Matrix (PMSC-ECM)
Indication
Myelomeningocele (MMC) -or Spina Bifida -diagnosed prenataly
Therapeutic Mechanism
Placenta-derived mesenchymal stem cells (PMSCs) act by a paracrine mechanism, secreting a variety of growth factors, cytokines, and extracellular vesicles. This secretory profile is unique to PMSCs and is responsible for protecting motor neurons from apoptosis, which occurs due to chemical and mechanical trauma when motor neurons are exposed to the intrauterine environment. PMSC treatment increases the density of motor neurons in the spinal cord, leading to improved motor function.
Unmet Medical Need
The current standard of care in utero surgery, while promising, still leaves 58% of patients unable to walk independently. There is an extraordinary need for a therapy that prevents or lessens the severity of the devastating and costly lifelong disabilities associated with the disease.
Project Objective
IND filing, Phase 1/2 trial start-up activities
Major Proposed Activities
- Manufacture product to supply the proposed studies and clinical trial
- Assess safety of the therapeutic PMSC product
- Assess efficacy using clinical-grade product
Statement of Benefit to California:
There is a high incidence of MMC in CA with 39.1% of the population being of Hispanic or Latino descent, a demographic that is affected by MMC at a disproportionately high rate. The cost to CA is approximately $532,000 per child, but for many, the cost may be several million dollars due to ongoing treatment. Indirect costs include pain and suffering, specialized childcare, and lost time of unpaid caregivers. A therapy for MMC would relieve the tremendous emotional and economic cost burden to CA.
Publications
- World J Stem Cells (2020): Clonal isolation of endothelial colony-forming cells from early gestation chorionic villi of human placenta for fetal tissue regeneration. (PubMed: 32184937)
- Fetal Diagn Ther (2020): A Decade of Experience with the Ovine Model of Myelomeningocele: Risk Factors for Fetal Loss. (PubMed: 32097922)
- J Pediatr Surg (2022): Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair. (PubMed: 35093254)
- J Pediatr Surg (2021): Efficacy of clinical-grade human placental mesenchymal stromal cells in fetal ovine myelomeningocele repair. (PubMed: 34217509)
- J Surg Res (2022): Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells. (PubMed: 35093836)
- J Pediatr Surg (2021): Long-term safety evaluation of placental mesenchymal stromal cells for in utero repair of myelomeningocele in a novel ovine model. (PubMed: 34657738)
- Lab Anim (2021): Minimizing the risk of occupational Q fever exposure: A protocol for ensuring Coxiella burnetii-negative pregnant ewes are used for medical research. (PubMed: 33108940)
- FASEB J (2019): Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes. (PubMed: 30753093)
- Fetal Diagn Ther (2021): A Novel Model of Fetal Spinal Cord Exposure Allowing for Long-Term Postnatal Survival. (PubMed: 34111873)
- J Surg Res (2021): Placental Mesenchymal Stromal Cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair. (PubMed: 34273796)
- Fetal Diagn Ther (2019): Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele. (PubMed: 30970373)
- Fetal Diagn Ther (2020): Surviving Lambs with Myelomeningocele Repaired in utero with Placental Mesenchymal Stromal Cells for 6 Months: A Pilot Study. (PubMed: 33166951)
- Cells (2021): The Unique Properties of Placental Mesenchymal Stromal Cells: A Novel Source of Therapy for Congenital and Acquired Spinal Cord Injury. (PubMed: 34831060)
- J Pediatr Surg (2019): In Utero Treatment of Myelomeningocele with Placental Mesenchymal Stromal Cells – Selection of an Optimal Cell Line in Preparation for Clinical Trials. (PubMed: 31672407)
