AT RISK FOR MS - Clinical Conversion of Female Monozygotic Twins Discordant for CIS/MS
Condition: Multiple Sclerosis; Clinically Isolated Syndrome
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Observational

Summary: 
      The definition of the most 'at-risk' population within highly susceptible groups would
      provide an opportunity for preemptive therapeutics.

      A convenient, safe, and tolerable therapy that delays the onset of clinical disease during
      the pre-symptomatic stage of demyelinating disease would provide a therapeutic alternative to
      a 'wait and see' approach in subjects at 'high risk' for CIS (clinically isolated syndrome -
      monosymptomatic demyelinating disease) or MS.

      Identical twins share the same genes and have the highest rate of shared MS. An identical
      female with a sister twin with MS has a 34% chance of having MS. Non concordant (no MS yet)
      identical (monozygotic - from the same sperm-egg zygote) female twins provide an ideal
      population to find out what factors predict the onset of MS in the non-affected twin.

      We will recruit 30 identical female twins, one with MS and the other without MS, and obtain
      brain MRI and biological samples on the non-affected twin and determine if:

        -  the presence of characteristic MS-like lesion(s) on baseline MRI predisposes to MS.

        -  specific proteins in blood or cerebrospinal fluid predispose to the clinical expression
           of demyelinating disease

      If we can predict by simple tests (MR brain scan and blood tests) the likelihood of the onset
      of MS in 'at risk' subjects, and have safe and tolerable therapies, we may be able to prevent
      the clinical onset of demyelinating disease (MS).
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        female monozygotic twins discordant for CIS/MS
      
Biospecimen description: 
      blood for serum and peripheral mononuclear cells; optional CSF - cerebrospinal fluid at entry
      and exit from trail
    
Keywords: demyelinating disease; multiple sclerosis; female monozygotic identical twins; MS; non-concordant; clinically isolated syndrome - CIS; brain MRI; proteomics