Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

The specific aims are:

1. To determine the effects of Tysabri on cognition (memory, thought processes, etc.)

2. To determine the effects of Tysabri on specific MRI markers for cognitive dysfunction

3. To determine the effects of Tysabri on retinal nerve fiber layer thickness (RNFL) using
optical coherence tomography (OCT), a special instrument used in ophthalmology

Inclusion Criteria:

- 18 through 60 years of age inclusive

- Diagnosis of relapsing remitting multiple sclerosis

- Prior to treatment phase, have had disease activity with at least 1 documented relapse
during the previous year OR 2 documented relapses during the previous 2 years OR one
or more new MRI lesions (Gd+ and/or T2 hyperintense)

- An Expanded Disability Status Scale (EDSS) score of 0-4.5 inclusive

- Neurologically stable with no evidence of relapse or corticosteroid treatment within
30 days prior to treatment

- Never been treated with Tysabri/natalizumab.

Exclusion Criteria:

- Another type of MS other than relapsing remitting multiple sclerosis (RRMS)

- A history of chronic disease of the immune system other than MS or a known
immunodeficiency syndrome/immunocompromised

- A history or presence of cancer (except for successfully treated basal or squamous
cell carcinoma of skin)

- Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis
B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface
antigen or Hepatitis C antibody tests, respectively

- Have received any live or live attenuated vaccines (including for varicella-zoster
virus or Measles) within the last 2 months

- Have received total lymphoid irradiation or bone marrow transplantation

- Have been treated with: corticosteroids or adrenocorticotropic hormones (ACTH) within
the last month, IFN-β or glatiramer acetate within the last 3 months,
immunosuppressive medications such as azathioprine or methotrexate within the last 6
months, immunoglobulins and/or monoclonal antibodies (including natalizumab) within
the last 6 months, or cladribine, cyclophosphamide or mitoxantrone at any time.

- Any medically unstable condition or a progressive neurological disorder, other than
MS, which may affect participation in the study

- History of any clinically significant cardiac, endocrinologic, hematologic, hepatic,
immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric,
renal or other major disease

- Unable to undergo MRI scans, including claustrophobia, have a pacemaker or history of
hypersensitivity to gadolinium-DTPA

- Have had a relapse within 30 days prior AND/OR not stabilized from a previous relapse

- History of severe allergic or anaphylactic reactions or known drug hypersensitivity to
natalizumab/Tysabri

- A clinically significant infectious disease, such as cellulitis, pneumonia, septicemia

- History of progressive multifocal leukoencephalopathy(PML)

- Participation in any clinical research study evaluating another investigational drug
or therapy within the last 6 months

- History of Tysabri therapy

- Abnormal screening blood test

- Females who are not postmenopausal for at least 1 year, surgically sterile or willing
to practice effective contraception during the study

- Nursing mothers, pregnant women, and women planning to become pregnant while on study