Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

The specific aims are:

• To determine the effects of Tysabri on cognition (memory, thought processes, etc.)
• To determine the effects of Tysabri on specific MRI markers for cognitive dysfunction
• 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