Analysis of Lymphocyte Cell Surface Adhesion Marker Expression in Natalizumab Population With Active Control

Patients at various timepoints in their MS treatment or who are beginning certain MS
treatments will be consented and have blood specimens collected to allow for an
immunological comparison. The decision to treat with disease modifying therapies is made
independently from this observational study.

Primary endpoint: To further understand the delineation of lymphocyte cell adhesion marker
down regulation within a treatment naïve patient population and at various stages of
treatment.

Secondary endpoint: To understand the correlation between natalizumab pharmacodynamics,
pharmacokinetics and lymphocyte cell adhesion marker down regulation.

The results of various biomarkers and immunological testing (including CD62L, LFA-1, sCD62L,
sLFA-1, sVCAM, VLA-4 saturation, IgG4, CBC with absolute differential) will be compared
amongst the groups consented. The treatment naive group will be compared longitudinally.

Inclusion Criteria:

1. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (PHI) in
accordance with national and local subject privacy regulations.

2. Aged 18 to 80 years old, inclusive, at the time of informed consent.

3. Patients with a relapsing form of Multiple Sclerosis as determined by the treating or
back-up neurologist per chart review.

4. If getting natalizumab or scheduled to commence natalizumab infusion the patient must
be enrolled in the TOUCH Prescribing Program and who is not expected to discontinue
Tysabri® therapy prior to completion of the requirements of this study or must be
currently prescribed and using interferon beta 1a or glatiramer acetate injections
for 18 months; or, naïve to natalizumab, interferon beta 1a or glatiramer acetate and
beginning treatment after consent.

5. Patients screened for Group A must be completely naïve to natalizumab, patients
beginning interferon beta-1a or glatiramer acetate must also be naïve to natalizumab.

6. Patients screened for natalizumab naïve must have at least 30 days clear of other
disease modifying therapies.

7. Patients must be free of known systemic bacterial or viral infections.

8. No fever over 99.5 degrees Fahrenheit in the last two weeks or at Baseline or prior
to any scheduled specimen collection.

9. No herpes zoster outbreaks within the last 30 days.

10. No methylprednisolone sodium succinate infusion (solumedrol) or corticosteroid use
within the last 30 days.

11. Must weigh between 44 and 190 kg, inclusive.

Exclusion Criteria:

1. Patient is unwilling or unable, in the opinion of the investigator, to comply with
study instructions.

2. Patients experiencing a MS relapse or exacerbation which results in
methylprednisolone sodium succinate infusion 30 days prior to Baseline

3. Patients with active, unknown infection etiology - if a patient is being treated for
a known infection this would be allowed at the discretion of the Investigator, but if
they present with signs of infection that has not been diagnosed they should be
excluded.

4. Fever of 99.6 or higher within the last two weeks prior to any of the scheduled
specimen collection (Baseline, 1 month, 3 month, 12 month or 18 month).

5. If patient has missed doses of their DMT as per the inclusion criteria.

6. No prior immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate,
cyclophosphamide, mycophenolate mofetil).

7. Specimen collection must occur Monday through Thursday.