442
patients if the T cell receptor activation pattern of each patient is determined at dif-
ferent stages of the disease. The BEST-PGx (Betaferon/Betaseron in Early relapsing-
remitting MS Surveillance Trial-Pharmacogenomics) has investigated the value of
RNA expression profi ling and pharmacogenetics in predicting treatment response to
interferon beta in patients with early relapsing MS (Kappos et al. 2005 ).
Genome-wide expression studies in brain tissue and blood samples of MS
patients are expected to reveal biomarkers that would help to determine disease
course, outcome, or treatment response in early stages of the disease (Habek et al.
2010 ). An increasing number of genetic polymorphisms have been correlated with
MS but so far their relevance to diagnosis of MS is rather low. A large number of
genes (including GSTM, IL1B, PD-1, CCR5, OPN, IL4, HLA-DRB1*1501, CD24,
ESR1, CD59, CNTF, CRYAB, IFNγ, MEFV, APOE, TGFB1) have been associated
with certain MS phenotypes but these correlations are often controversial. Research
on pharmacogenomics of MS is increasing but has not produced a useful biomarker
for clinical practice so far (Comabella and Vandenbroeck 2011 ).
Immunopathological Patterns of Demyelination
for Assessing Therapy
Early, active multiple sclerosis lesions show several immunopathological patterns
of demyelination, which may explain differences in response to therapy in various
patients. Therapeutic plasma exchange (TPE) has been successfully used to treat
fulminant demyelinating attacks unresponsive to steroids. A Mayo Clinic study
demonstrated that patients with pattern II would be more likely to improve after
TPE than those with other patterns since pattern II lesions are distinguished by
prominent immunoglobulin deposition and complement activation. This is the fi rst
evidence that differences in pathological subtypes of MS may predict response to
treatment. Correlation of plasma exchange response to tissue pathology supports
the hypothesis that different patterns of tissue damage in MS may require different
treatment approaches. However, brain biopsies such as those undergone by the
patients studied are not routinely done in MS patients. They are only performed for
excluding other diagnoses such as tumor or infection. Therefore, it is necessary to
identify specifi c biomarkers from blood, DNA or MRI, which can distinguish
between these four patterns without the need for a brain biopsy.
Personalizing Mitoxantrone Therapy of Multiple Sclerosis
Numerous studies have shown that mitoxantrone (MX), an anticancer agent, is
highly effi cient in suppressing disease activity in multiple sclerosis. It is adminis-
tered as escalation therapy when other medication no longer suffi ces and in
12 Personalized Management of Neurological Disorders