Human Umbilical Cord
Mesenchymal Stem Cells
for Multiple Sclerosis

 

Clinical Trial

Translational Biosciences DRAFT logo 3Translational Biosciences, a wholly-owned subsidiary of Medistem Panama is no longer recruiting patients for this trial.


Feasibility Study of Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in Patients with Multiple Sclerosis

Abstract

Umbilical cord tissue derived mesenchymal stem cells (UC-MSC), are an immune modulatory cell population that has demonstrated therapeutic activity in animal models of autoimmunity [1, 2], as well as clinical trials [3, 4]. Mechanistically, UC-MSC produce anti-inflammatory and immune modulatory factors, which appear to be therapeutic in the context of autoimmunity[5]. Additionally, UC-MSC produce neurotrophic mediators that enhance myelin production and/or prevent neuronal apoptosis[6].

While safety of UC-MSC administered intravenously is established, it is unknown whether these cells are effective in treatment of multiple sclerosis (MS). A case report suggested therapeutic benefit [7], however no formal trials have been conducted.

The proposed study seeks to determine safety and efficacy of 100 million intravenously administered UC-MSC cells in patients with multiple sclerosis. Safety will be defined as freedom from treatment associated adverse events. Efficacy parameters, which will be assessed at weeks 12 and 52 will comprise endpoints of EDSS, expanded EDSS (Rating Neurologic Impairment in Multiple Sclerosis), the Scripps neurological rating scale (NRS), paced auditory serial addition test (PASAT) (Fischer, Jak, Kniker, Rudick, Cutter, 2001), the nine-hole peg test, 25-foot walking time, short-form 36 (SF-36) quality of life questionnaire and gadolinium enhanced MRI scans of the brain and cervical spinal cord.

This, study will provide support for double-blind placebo controlled investigations. The potential of using UC-MSC for this debilitating condition will open the door for future investigations in other inflammatory conditions if results demonstrate safety and feasibility of this approach.

Inclusion Criteria

  • Patients willing to sign informed consent and capable of understanding the features of this clinical trial.
  • Willing to keep a weekly diary and undergo observation for 12 months
  • Non-pregnant patients 18-55 years of age with MS according to the revised McDonald criteria and meeting the Possner criteria for clinically defined MS.
  • EDSS scores of 2·0 to 5·5 points assessed at least 3 months after the last acute attack of MS.
  • Must have proof of health insurance in country of residence.

 

Exclusion Criteria

  • Patients with evidence of active proliferative retinopathy.
  • Patients with poorly controlled diabetes mellitus (HbA1C > 8.5%).
  • Patients with renal insufficiency (Creatinine> 2.5) or failure.
  • Infection as evidenced by WBC count of >15,000 k/cumm and/or temperature >38C.
  • History of organ transplant.
  • History of previous or active malignancy, except for localised cutaneous basal or squamous cell carcinoma or carcinoma in situ of the cervix
  • Cardiovascular conditions:
    • Exercise limiting angina ( Canadian Cardiovascular Society Class 3
    • Congestive heart failure (New York Heart Association class 3
    • Unstable angina
    • Acute ST elevation myocardial infarction (MI) within 1month
    • Transient ischemic attack or stroke within 1 month

As seen on ClinicalTrials.gov

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


References

  1. Anzalone, R., et al., Wharton’s jelly mesenchymal stem cells as candidates for beta cells regeneration: extending the differentiative and immunomodulatory benefits of adult mesenchymal stem cells for the treatment of type 1 diabetes. Stem Cell Rev, 2011. 7(2): p. 342-63.
  2. Liu, R., et al., Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination. Stem Cells Dev, 2013. 22(7): p. 1053-62.
  3. Hu, J., et al., Long term effects of the implantation of Wharton’s jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocr J, 2013. 60(3): p. 347-57.
  4. Ma, L., et al., Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients. Thromb Haemost, 2012. 107(5): p. 937-50.
  5. Najar, M., et al., Adipose-tissue-derived and Wharton’s jelly-derived mesenchymal stromal cells suppress lymphocyte responses by secreting leukemia inhibitory factor. Tissue Eng Part A, 2010. 16(11): p. 3537-46.
  6. Weiss, M.L., et al., Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells, 2006. 24(3): p. 781-92.
  7. Liang, J., et al., Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis. Mult Scler, 2009. 15(5): p. 644-6.