445analyses to determine the genetic elements controlling MS. The data from this study
suggest that early initiation of treatment with IFN-β1b prevents the development of
confi rmed disability, supporting its use after the fi rst manifestation of relapsing-
remitting multiple sclerosis (Kappos et al. 2007 ). Expression levels of IFN response
genes in the peripheral blood of MS patients prior to treatment could serve a role as
biomarker for the differential clinical response to IFN-β (van Baarsen et al. 2008 ).
Biomarkers will enable responders and nonresponders to drugs to be identifi ed,
increase the effi cacy and compliance, and improve the pharmaco-economic profi le
of these drugs. Systems biology can be used to integrate biological and clinical data
for developing personalized treatment of MS.
Genome-wide expression profi les of peripheral blood mononuclear cells of mul-
tiple sclerosis patients within the fi rst 4 weeks of IFN-β administration identifi ed
121 genes that were signifi cantly up- or downregulated compared with baseline,
with stronger changed expression at 1 week after start of therapy (Hecker et al.
2012 ). Eleven transcription factor-binding sites (TFBS) are overrepresented in the
regulatory regions of these genes, including those of IFN regulatory factors and
NF-κB. TFBS-integrating least angle regression, a novel integrative algorithm for
deriving gene regulatory networks from gene expression data and TFBS informa-
tion, was then applied to reconstruct the underlying network of molecular interac-
tions. A NF-κB-centered sub-network of genes was highly expressed in patients
with IFN-β-related side effects.
Understanding of the factors that underlie therapeutic response is the key to iden-
tifi cation of predictive biomarkers. Novel developments in pharmacogenomics
research are helping to improve the understanding of the pharmacological effects of
IFN therapy, and the identifi cation of biomarkers that allow stratifi cation of MS
patients for their response to IFN-β (Martinez-Forero et al. 2008 ). Ultimately, this
information will lead to personalized therapy of MS (Vosslamber et al. 2009 ).
Expression of gene as biomarkers of response to IFN-β therapy in multiple sclerosis
is shown in Table 12.7.
T Cell-Based Personalized Vaccine for MS
Tcelna® (Opexa Therapeutics) is a T cell-based personalized autologous immuno-
therapy. It consists of attenuated, patient-specifi c myelin reactive T-cells (MRTCs)
against peptides of the 3 primary myelin proteins: myelin basic protein (MBP),
myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP) that
have been implicated in T cell pathogenesis of MS. Prior to use, the MRTCs are
expanded, formulated, and attenuated (by irradiation) to render them unable to rep-
licate but viable for therapy. These attenuated T cells are administered in a defi ned
schedule of fi ve subcutaneous injections. Patients are expected be treated with a
new vaccine series each year based on their altered disease profi le or epitope shift.
This vaccine is currently in phase III clinical trials.
Personalized Treatment of Multiple Sclerosis