Stem Cells in Rapidly Evolving Active Multiple Sclerosis

Inclusion Criteria

Patients with clinically and radiologically active multiple sclerosis as defined by:

• Diagnosis of MS:
• Relapsing remitting MS (RRMS): ≥ 1 moderate-severe relapse and ≥1 GEL in past 18 months or ≥ 1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.
• Secondary progressive MS (SPMS) with an increase of ≥ 1 EDSS point (if baseline EDSS ≤ 5) or 0.5 EDSS point (if baseline EDSS ≥ 5.5), in the previous 18 months and ≥ 1 GEL in past 18 months or ≥ 1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.
• Primary progressive MS (PPMS) patients with positive oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) and an increase of ≥ 1 EDSS point (if baseline EDSS is ≤ 5.0) or 0.5 EDSS point (if baseline EDSS is ≥ 5.5), or quantifiable, objective evidence of equivalent progression in the previous 18 months and ≥ 1 GEL in past 18 months or ≥ 1 new T2 lesion in past 18 months.
• Age 18 to 50 years.
• Disease duration 2 to 10 years from diagnosis (inclusive).
• Expanded Disability Status Scale (EDSS) 2.0 to 6.5 at screening evaluation.
• ≥ 1 GEL on MRI within 6 months prior to harvesting.
• Adequate culture of a subject's MSCs and their release for clinical use.

Exclusion Criteria

• RRMS without at least one severe relapse in the previous 18 months or without at least one GEL or one new T2 in the previous 18 months.
• SPMS without relapses and without new lesions (GEL or T2 positive) at MRI in the last 18 months.
• PPMS without positive CSF OCBs or without a GEL or new T2 lesion in the previous 18 months.
• No gadolinium enhancing lesion(s) in the 3 months prior to bone marrow harvesting.
• A previously ineligible patient who failed to meet the MRI requirements of the inclusion criteria will not be reviewed again even if further imaging, revealing ≥ 1 GEL, becomes available.
• Failure of bone marrow (BM) sample to generate MSCs suitable for clinical use within a specified time frame (4 weeks).
• Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the last 3 months.
• Treatment with interferon-beta or glatiramer acetate within the last 1 month.
• Treatment with alemtuzumab (campath-1H) within the last 2 years.
• Prior treatment with total lymphoid irradiation and autologous or allogeneic hematopoietic stem cell transplantation.
• Participation in clinical trials of any experimental drugs in the 6 months before study entry.
• Corticosteroid treatment in the last 30 days.
• Presence of any active or chronic infection.
• Previous history of a malignancy other than basal cell carcinoma of the skin and carcinoma in situ that has been in remission for more than one year.
• Severely limited life expectancy by any other co-morbid illness.
• Abnormal blood counts, a history of myelodysplasia or other cytopenia.
• Known pregnancy, positive urine pregnancy test at screening or risk or pregnancy (this includes patients who are unwilling to practice active contraception during the duration of the study).
• Contraindication to MRI including but not limited to intracranial aneurysm clips (except Sugita), history of intra-orbital metal fragments that have not been removed by an MD (as confirmed by orbital X-Ray), pacemaker and non-MRI compatible devices (e.g. heart valves, inner ear implants), history of claustrophobia or the inability of the subject to lie still on their back for a period of 1.5 hours in the MRI scanner.
• An estimated glomerular filtration rate (eGFR)< 60 mL/min/1.73m2 or history or presence of renal impairment (e.g. serum creatinine clearance less than 30ml/min).
• Inability to give written informed consent/comply with study procedures.
• Any significant organ dysfunction or co-morbidity that the Investigators consider would put the subject at unacceptable risk by participating in the study or that would interfere with the functional assessments.