Inclusion Criteria

- INCLUSION CRITERIA:

MS as defined by the modified McDonald's criteria (Polman, Reingold et al. 2005)

SP-MS as documented by lack of MS relapse for the past 1 year and non-remitting/sustained
(> 3 months) progression of disability

Age 18-65, inclusive, at the time of the first screening baseline visit

EDSS 3.0 to 7.0, inclusive, at the time of the first screening baseline visit

Able to provide informed consent

Willing to participate in all aspects of trial design and follow-up

Lack of CEL on all MRIs performed within the last 12 months or if patient has CEL, then
documentation that they tried and failed or could not tolerate FDA approved disease
modifying therapies (DMTh)

Not receiving any DMTh (such as IFN-beta preparation, glatiramer acetate, corticosteroid,
natalizumab, fingolimod, immunosuppressive agents or experimental therapeutics) for a
period of at least 1 month before enrollment in the study, allowing for at least a 1-year

period off therapy prior to the first study dose

Agreeing to commit to the use of a reliable/accepted method of birth control (i.e.
hormonal contraception (birth control pills, injected hormones, vaginal ring),
intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom
with spermicide) or they have undergone surgical sterilization (such as hysterectomy,
tubal ligation, or vasectomy)) during enrollment in the study and through 12 months after
the last dose of study drug

EXCLUSION CRITERIA:

RR-MS or PP-MS

Evidence of clearly documented MS relapse within the last 1 year

Alternative diagnoses that can explain neurological disability and MRI findings

Clinically significant medical disorders that, in the judgment of the investigators could
cause CNS tissue damage, limit its repair, expose the patient to undue risk of harm or
prevent the patient from completing the study (such as, but not limited to cerebrovascular
disease, ischemic cardiomyopathy, clotting disorder, brittle diabetes, neurodegenerative
disorder)

Pregnant or breastfeeding female

History or sign of congenital or acquired immunodeficiency or chronic infections, such as
HIV/AIDS, Hepatitis A, B or C, HTLV-1 carrier and others that would expose patient to
risks of pathogen reactivation associated with rituximab treatment

Abnormal screening/baseline blood tests exceeding any of the limits defined below:

1. Serum alanine transaminase or aspartate transaminase levels which are greater than
three times the upper limit of normal values.

2. Total white blood cell count < 3 000/mm(3)

3. Platelet count < 85 000/mm(3)

4. Serum creatinine level > 2.0 mg/dl and eGFR (glomerular filtration rate) < 60

5. Serological evidence of HIV, HTLV-1 or active hepatitis A, B or C

6. Positive pregnancy test

7. Positive CSF or serum quantitative PCR for JC virus on CSF collected from the
baseline spinal tap (test will be performed by CLIA certified laboratory of Gene
Major, NINDS)

8. Total serum IgG < 600mg/dl (nl 642-1730mg/dl) or total serum IgM < 30mg/dl (nl
34-342mg/dl) as these Ig deficiencies would suggest underlying abnormalities with B
cell function/maturation