Phase I-II Clinical Trial With Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis

Treatment tested

• Bone marrow autologous mesenchymal stem cells transplantation

Other measures (14)

Inclusion Criteria: * Relapsing-remitting MS (RRMS) patients * Age 18-50 years * Disease duration >= 2 and \<= 10 years * EDSS: 3.0 - 6.5 * 1) Patients who do not wish to be subjected to approved immunomodulatory treatments (interferon beta and acetato de glatiramer) 2) Patients who have tried and had to withdraw within a year due to adverse events 3) Patients who have not responded to them after at least 1 year of continuous treatment. Lack of response is considered one or more of the following * >= 1 moderate-severe relapses in past 12 months * >= 2 moderate-severe relapses in past 24 months * >= 1 Gadolinium enhancing lesions in a MRI performed in previous 12 months Relapse: * Mild: Increase of \< 1 EDSS point * Moderate: Increase of >= 1 EDSS point (if baseline EDSS 3.0-5.0) or 0.5 EDSS points (if baseline EDSS >= 5.5) * Severe: Increase of >=3 EDSS point * Social, mental and physical ability to communicate with physicians and to understand the requirements of the protocol * Has given informed consent to participate in the study Exclusion Criteria: * RRMS not fulfilling inclusion criteria * SPMS or PPMSTreatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization * Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization * Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization * Treatment with corticosteroids within the 30 days prior to randomization * Relapse occurred during the 60 days prior to randomization * History of cancer or clinical or laboratory results indicative of severe systemic diseases, including infection for HIV, Hepatitis B or C * Pregnancy or risk of pregnancy/ lactation * Current treatment with an investigational therapy * Inability to give written informed consent in accordance with research ethics board guidelines

Immunomodulatory therapies to treat the relapsing-remitting phase of multiple sclerosis (MS) are designed to ameliorate the inflammatory processes that mediate the damage to the central nervous system (CNS) and to delay progression of the disease. To date, there is no effective means to stop the progression of disease and induce remyelination. Adult stem cells therapy show great promise and is rapidly developing as alternative therapeutic strategy. We propose the use of bone marrow-derived autologous Mesenchymal (BM-MSC) Stem Cells transplantation to treat patients with relapsing-remitting MS (RRMS), despite immunomodulatory therapy. Taking advantage of the potential that MSC possess strong immunomodulatory properties thought to play a role in the maintenance of peripheral tolerance and in the control of autoimmunity and that may stimulate repair and regeneration of lesions, we plan a trial of a single injection of autologous BM-MSC into eight patients. First, we aim to assess the feasibility, safety and tolerability of autologous MSC therapy in RRMS. Second, we plan to evaluate the effects of BM-MSC transplantation on MS disease activity by clinical, neurophysiological, immunological and imaging assessments. Autologous MSC will be obtained from bone marrow aspirates, purified by culture and characterized by surface antigen expression. A single dose of autologous BM-MSC will be injected intravenously. Clinical, neurological and immunological assessments will be scheduled at baseline (before BM-MSC transplantation) at 1, 3, and 6 months after transplant. The imaging will be performed at 3 and 6 months after transplant. Proposed trial will enable us to ascertain whether autologous BM-MSC transplantation is a feasible and safe procedure, and whether BM-MSC can establish an environment of immune tolerance and through the local production of neurotrophic/growth factors, might induce neuroprotection and improvement in CNS function.