Grant Award Details
File an IND application for a clinical trial using allogeneic placental MSC to augment fetal myelomeningocele repair.
Grant Application Details
- Placental Mesenchymal Stem Cell Augmentation of Fetal Myelomeningocele Repair
Therapeutic Candidate or Device
Allogeneic Placenta-derived Mesenchymal Stem Cells Seeded on Cook Biodesign® Dural Graft Extracellular Matrix (PMSC-ECM)
Myelomeningocele (MMC) -or Spina Bifida -diagnosed prenataly
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.
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
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.
- Bioact Mater (2023) A bioactive material with dual integrin-targeting ligands regulates specific endogenous cell adhesion and promotes vascularized bone regeneration in adult and fetal bone defects. (PubMed: 35663336)
- J Pediatr Surg (2022) Early investigations into improving bowel and bladder function in fetal ovine myelomeningocele repair. (PubMed: 35093254)
- J Surg Res (2022) Impact of Gestational Age on Neuroprotective Function of Placenta-Derived Mesenchymal Stromal Cells. (PubMed: 35093836)
- Bioengineering (Basel) (2022) Engineering Extracellular Microenvironment for Tissue Regeneration. (PubMed: 35621480)
- Theranostics (2022) Engineered extracellular vesicles with high collagen-binding affinity present superior in situ retention and therapeutic efficacy in tissue repair. (PubMed: 35966577)
- 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 (2021) Long-term safety evaluation of placental mesenchymal stromal cells for in utero repair of myelomeningocele in a novel ovine model. (PubMed: 34657738)
- J Surg Res (2021) Placental Mesenchymal Stromal Cells: Preclinical Safety Evaluation for Fetal Myelomeningocele Repair. (PubMed: 34273796)
- J Pediatr Surg (2021) Efficacy of clinical-grade human placental mesenchymal stromal cells in fetal ovine myelomeningocele repair. (PubMed: 34217509)
- Fetal Diagn Ther (2021) A Novel Model of Fetal Spinal Cord Exposure Allowing for Long-Term Postnatal Survival. (PubMed: 34111873)
- 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)
- Fetal Diagn Ther (2020) Surviving Lambs with Myelomeningocele Repaired in utero with Placental Mesenchymal Stromal Cells for 6 Months: A Pilot Study. (PubMed: 33166951)
- 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)
- FASEB J (2019) Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes. (PubMed: 30753093)
- 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)
- Fetal Diagn Ther (2019) Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele. (PubMed: 30970373)