Safety and Feasibility Study
Cell Therapy
for Spinal Cord Injury

 

Clinical Trial

Translational Biosciences DRAFT logo 3Translational Biosciences, a wholly-owned subsidiary of Medistem Panama is currently recruiting patients for this IRB-approved clinical trial. We encourage anyone suffering from autism who meets the inclusion/exclusion criteria below to apply.


Safety and Feasibility Study of Cell Therapy in Treatment of Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is caused by direct mechanical damage to the spinal cord that usually results in complete or incomplete loss of neural functions such as mobility and sensory function. To date, no therapy exists to induce recovery in subjects with SCI.

Although endogenous repair mechanisms are activated after SCI, such as proliferation of endogenous stem cells [1-3], their activity is in many times clinically insignificant. Administration of mesenchymal stem cells (MSC) in animal models of SCI induces a therapeutic benefit by: a) production of trophic factors that inhibit inflammation and induce endogenous neurogenesis [4]; b) differentiate into, or stimulating endogenous cells to differentiate into myelin-forming cells [5, 6]; and c) providing an environment suitable for axon regeneration through inhibition of fibrosis [7] and stimulation of angiogenesis [8, 9].

Clinical trials using MSCs [10-12] as well as bone marrow mononuclear cells (BMMC) [13-17]
have demonstrated safety and signals of efficacy in subjects with SCI. In the proposed study, we seek to assess the safety and potential benefit of a combination therapy using umbilical cord tissue MSCs (UC-MSC) together with autologous BMMC administered intrathecally and intravenously. We have successfully reported a variation of this protocol in a case report [18]. In contrast to other studies, the combination of intrathecal and intravenous administration provides a minimally invasive regenerative protocol that can be widely employed.

The proposed study seeks to determine safety and efficacy of stem cells administered to 20 male or female SCI subjects between the ages of 18 and 50. Safety will be defined as freedom from treatment associated serious adverse events. Efficacy parameters, which will be assessed at baseline, Month 3 and Month 12, will comprise endpoints of acute spinal cord injury Frankel classification grading system and American Spinal Cord Injury Association (ASIA) International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).

This study will provide support for double-blind placebo controlled investigations. The potential of using cell based therapy for SCI will provide a research direction for a condition that currently represents an unmet medical need.

This protocol will be conducted under the safety standards and in accordance with the guiding principles of GCP and adequate human subject protection, as well as with local and international policies and regulations that govern the discipline of clinical research and use of stem cells

Inclusion Criteria

  • Men and women between age 18 and 50
  • Paraplegics and quadriplegics with complete or incomplete spinal cord injuries.
  • Willingness to undergo bone marrow derived autologous cell therapy.
  • Ability and willingness to make regliar visits to hospital and follow ups during the protocol procedure and comply with all medical instructions
  • Traumatic Injury of spinal cord with complete or partial damage by Magnetic Resonance Imaging (MRI) and injury level below C4
  • ASIA impairment scale from A – C
  • Must have proof of health insurance in country of residence.
  • Signed informed consent

Exclusion Criteria

  • Pre- existing or current systemic disease such as lung, liver (exception: history of uncomplicated hepatitis A), gastrointestinal, cardiac, Human Immunodeficiency Virus (HIV)
  • History of life threatening allergic- or immune-mediated reaction
  • Hemodynamic instability
  • Peripheral muscular dystrophy
  • Lactating or pregnant woman
  • Women capable of childbearing unwilling to use multiple forms of contraception
  • Alcohol drug abuse /dependence
  • Positive test result for hepatitis A and Hepatitis B OR C
  • Major-traumatic brain injury and psychiatric illness
  • Open injuries
  • Active infectious diseases
  • Life expectancy of less than one year due to terminal condition
  • Neurodegenerative diseases
  • Primary hematologic diseases
  • Any of the following medications that cannot be discontinued one week prior to the first stem cell administration and throughout the course of treatment. (1 week before visit 2 through one week after visit 12)
    • Antibiotics
    • Antifungals
    • Antivirals
    • Blood thinners (to avoid bleeding risk during bone marrow aspiration and IT procedures)
    • High doses of Vitamin D or fish oils (since these might prolong bleeding times)
  • Bone reflecting increased risk for spinal puncture
  • Hepatic dysfunction
  • Other medical complications that contraindicate surgery, including major respiratory complications
  • Participation in another clinical trial
  • Coagulopathies
  • Uncorrected coagulopathy during the baseline period defined as: International Normalized Ratio (INR) > 1.4; Partial Thromboplastin Time (PTT) > 35 sec; Platelet Count (PLT) < 100,000.
  • Pre-injury history of seizure disorder and/or neurological impairment where participation in age-appropriate pain rating scales would not be practical or possible
  • Subject does not sign informed consent form

As seen on ClinicalTrials.gov

View this clinical trial on National Institutes of Health ClinicalTrials.gov


References

  1. Hagg, T. and M. Oudega, Degenerative and spontaneous regenerative processes after spinal cord injury. J Neurotrauma, 2006. 23(3-4): p. 264-80.
  2. Matthews, M.A., M.F. St Onge, and C.L. Faciane, An electron microscopic analysis of abnormal ependymal cell proliferation and envelopment of sprouting axons following spinal cord transection in the rat. Acta Neuropathol, 1979. 45(1): p. 27-36.
  3. Bruni, J.E., Ependymal development, proliferation, and functions: a review. Microsc Res Tech, 1998. 41(1): p. 2-13.
  4. Park, S.I., et al., Human umbilical cord blood-derived mesenchymal stem cell therapy promotes functional recovery of contused rat spinal cord through enhancement of endogenous cell proliferation and oligogenesis. J Biomed Biotechnol, 2012. 2012: p. 362473.
  5. Steffenhagen, C., et al., Mesenchymal stem cells prime proliferating adult neural progenitors toward an oligodendrocyte fate. Stem Cells Dev, 2012. 21(11): p. 1838-51.
  6. Keilhoff, G., et al., Transdifferentiated mesenchymal stem cells as alternative therapy in supporting nerve regeneration and myelination. Cell Mol Neurobiol, 2006. 26(7-8): p. 1235-52.
  7. Veeravalli, K.K., et al., Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury. Neurobiol Dis, 2009. 36(1): p. 200-12.
  8. Quertainmont, R., et al., Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions. PLoS One, 2012. 7(6): p. e39500.
  9. Zeng, X., et al., Bone marrow mesenchymal stem cells in a three-dimensional gelatin sponge scaffold attenuate inflammation, promote angiogenesis, and reduce cavity formation in experimental spinal cord injury. Cell Transplant, 2011. 20(11-12): p. 1881-99.
  10. Bhanot, Y., et al., Autologous mesenchymal stem cells in chronic spinal cord injury. Br J Neurosurg, 2011. 25(4): p. 516-22.
  11. Park, J.H., et al., Long-term results of spinal cord injury therapy using mesenchymal stem cells derived from bone marrow in humans. Neurosurgery, 2012. 70(5): p. 1238-47; discussion 1247.
  12. Karamouzian, S., et al., Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg, 2012. 114(7): p. 935-9.
  13. Callera, F. and R.X. do Nascimento, Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury: a preliminary safety study. Exp Hematol, 2006. 34(2): p. 130-1.
  14. Geffner, L.F., et al., Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant, 2008. 17(12): p. 1277-93.
  15. Sykova, E., et al., Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant, 2006. 15(8-9): p. 675-87.
  16. Yoon, S.H., et al., Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial. Stem Cells, 2007. 25(8): p. 2066-73.
  17. Park, H.C., et al., Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Eng, 2005. 11(5-6): p. 913-22.
  18. Ichim, T.E., et al., Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report. Int Arch Med, 2010. 3: p. 30.