Mesenchymal Stem Cells for the Treatment of MS

NCT00781872 | Completed Phase 1

• 1 other identifier: MS22MSC-HMO-CTIL
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Although, effective immunotherapies for MS exist which downregulate the anti-myelin reactivity and reduce the rate of relapses of the disease, there is no effective means today to stop the progression of disability and induce remyelination. Neuronal stem cells were shown to possess the ability to restore neuronal activity and produce new neurons through transdifferentiation. Various other types of stem cells were tested in animal models with promising results, revealing a potential for restoration of the neurological function in neuroimmune and neurodegenerative conditions. Adult bone marrow derived stromal cells (MSC) were shown to induce similar (to neuronal stem cells) immunomodulatory and neuroregenerative effects and were shown in our laboratory to induce neuroprotection in the animal model of chronic experimental autoimmune encephalomyelitis (EAE). MSCs offer practical advantages for clinical therapeutic applications, since they can be obtained from the adult bone marrow and therefore the patient can be the donor for himself, without any danger for rejection of the cells. In addition, MSCs carry a safer profile and are less prone to malignant transformation. Our initial clinical experience with 10 patients with ALS and 10 with multiple sclerosis show that intravenous and intrathecal administration of MSCs is feasible and safe. In this study we propose an explorative protocol with the injection of MSCs (both intrathecally and intravenously) in patients with MS, in an effort to prevent further neurodegeneration through neuroprotective mechanisms and induce neuroregeneration and restoration of neuronal function. The primary endpoint will be to further evaluate the safety and feasibility of the treatment with MSC infusions, in MS patients. Additionally, the migration ability of the transplanted cells will be evaluated by tagging MSCs with the superparamagnetic iron oxide particle (Feridex) for detection by MRI. Clinically the patients will be followed by monthly evaluations of the MS functional rating scale (EDSS) scale. The MRI, will be also used to evaluate changes in the total volume of lesions in the brain and the degree of atrophy. Significance: This project may provide information for possible therapeutic uses of this type of bone marrow adult stem cells in MS but may also serve as a pilot platform and pave the path for future applications of various types of stem cells in neurodegerative diseases, in general.

Conditions

Multiple Sclerosis

Keywords

multiple sclerosis (MS); bone marrow stromal cells; stem cells

Outcome Measures

Primary Outcomes (1)

• Safety of one or multiple intrathecaland intravenous injections of autologous MSC in Multiple sclerosis

  Appearance of adverse events during the 1-4 years of follow up after one or multiple treatments with MSC

  One year for the first phase; 4 years for the extension phase

Secondary Outcomes (2)

• Clinical effects in terms of changes in the expended disability status scale (EDSS) at 3-6 month intervals

  One year for the first phase; 4 years for the extension phase

• Immunological effects of treatment with MSC in MS

  1-6 months after the first treatment with MSC

Study Arms (1)

Treatment with autologous mesenchymal stem cells (MSC) intrathecally and intravenously

EXPERIMENTAL

Intrathecal and intravenous treatment with autologous mesenchymal stem cells (MSC) intrathecally and intravenously in patients with active multiple sclerosis, failures to respond to other treatments

Biological: Injection of autologous bone marrow derived mesenchymal stem cells

Interventions

Injection of autologous bone marrow derived mesenchymal stem cells BIOLOGICAL

60 million cells intrathecally (approximately 1 million cells per Kg of body weight) and 20 million cells intravenously

Also known as: Mesenchymal stem cells of bone marrow

Treatment with autologous mesenchymal stem cells (MSC) intrathecally and intravenously

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consenting patients fulfilling the Poser's clinical criteria for definite MS
• Age: 35-65, males and females
• Duration of disease: \>5 years
• Failure to the currently available -registered- for MS immunomodulatory treatments (ie interferons, Copaxone, immunosuppression): the lack of response to (at least two) of these treatments will be determined/defined by either an increase (deterioration) of at least one degree in the EDSS score during the last year or the appearance of at least two major relapses of MS during the same period of time (under treatment).

You may not qualify if:

• Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results
• Patients with active infections
• Patients with severe cognitive decline or inability to understand and sign the informed consent

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Related Publications (1)

• Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94. doi: 10.1001/archneurol.2010.248.

  PMID: 20937945 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Dimitrios Karussis, Prof.

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of The Center for Multiple Sclerosis & Unit of Neuroimmunology

Study Record Dates

• First Submitted: October 28, 2008
• First Posted: October 29, 2008
• Study Start: October 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: March 29, 2021

Record last verified: 2021-03