AT RISK FOR MS - Clinical Conversion of Female Monozygotic Twins Discordant for CIS/MS

Primary Objective: Determine if the presence of characteristic MS-like lesion(s) on baseline MRI predisposes to CIS/MS in female MZ twins discordant for CIS/MS.

Secondary Objective: Define the protein and microarray gene expression profile predictive of conversion to MS/CIS in female MZ twins discordant for CIS/MS.

Design and Outcomes: This is a single center, clinical study to determine if the presence of MS-like MRI brain lesions predict the rate of conversion to CIS in female MZ twins discordant for CIS/MS.

We will screen and recruit 30 subjects, and begin to follow these subjects annually for a total of 5 years to determine if MR brain scans predict CIS/MS conversion.

Interventions and Duration: Subjects will be recruited over 2 years and followed for five years with annual neurological examinations and MR brain scans.

Sample Size and Population: 30 female co-twins discordant for CIS/MS will be studied. We predict 72% of the 27% 'at risk' subjects with characteristic MR brain lesions at baseline will convert to CIS within 5 years. We predict only 6% of the 73% 'at risk' subjects without characteristic MR brain lesions at baseline will convert to CIS within 5 years.

These data will determine if paraclinical (MRI) evidence of demyelinating disease and specific blood or cerebrospinal fluid proteins predict clinical expression of disease in highly susceptible populations predicts.

Inclusion criteria

• 'at risk' individuals for MS - female co-twins discordant for CIS/MS.
• 'at risk' individuals for MS who at the time of randomization have not converted to MS or CIS.
• 'at risk' individuals will be treatment-naïve for immunomodulatory/suppressive medications.
• < 46 years old.

Exclusion criteria

• Individuals diagnosed with MS or CIS.
• Other 'at risk' individuals who do not conform to the specific 'at risk' groups outlined above e.g., 1st degree, 2nd degree and 3rd degree relative of MS index cases.
• Subjects over 45.
• Use of immunomodulatory medications such as azathioprine, gold, sulfasalazine, minocycline, statins, and MTX or prednisone > 7.5 mg/day within 30 days of randomization for any reason.
• Active drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or a psychiatric disorder that is unstable or would preclude reliable participation in the study.
• Serious illness (requiring systemic treatment and/or hospitalization) such as diabetes mellitus, renal, cardiac, or pulmonary disease. Subjects with a history of alcoholism, or in whom intellectual functioning is impaired sufficiently to interfere with the understanding of the protocol, or participation in the treatment and evaluation program.