Textbook of Personalized Medicine - Second Edition [2015]

(Ron) #1

444


Fusokine Method of Personalized Cell Therapy of Multiple Sclerosis


Fusokine (GIFT15), a cytokine prepared by fusion of granulocyte-macrophage col-
ony–stimulating factor (GM-CSF) with interleukin-15 (IL-15), exerts immune sup-
pression via aberrant signaling through the IL-15 receptor on lymphomyeloid cells.
This is reverse of immune stimulating effect of either GM-CSF or IL-15 when given
singly. Ex vivo GIFT15 treatment of mouse splenocytes converts B cells, normally
involved in immune response, into powerful immune-suppressive cells termed
GIFT15 Breg cells (Rafei et al. 2009 ). Unlike T-cells, naturally-occurring immune-
suppressing B cells are almost unknown in nature and the idea of using them to
control immunity is novel. In this study, mice with experimental autoimmune
encephalomyelitis went into complete remission after intravenous infusion of
GIFT15 Breg cells paralleled by suppressed neuroinfl ammation. There were no sig-
nifi cant side-effects in the mice and the treatment was fully effective with a single
dose. Autologous GIFT15 Breg cells may serve as a new treatment for autoimmune
diseases such as multiple sclerosis. Unlike earlier immune-suppressing therapies
that rely on drugs, this approach is a personalized form of cellular therapy, which
uses the body’s own cells to suppress immunity in a more targeted manner. B-cells
can be isolated from a patient’s blood sample, purifi ed in the laboratory, treated with
GIFT15 in a petri dish, and administered back to the patient. Multiple sclerosis
should be treated with this method in its earliest stages. Clinical trials are needed to
test the treatment’s effi cacy and safety in humans.


Pharmacogenomics of IFN-β Therapy in Multiple Sclerosis


Affymetrix 100 K SNP arrays have been used to identify 18 SNPs that may explain
why some individuals respond better to IFN-β treatment for MS than others (Byun
et al. 2008 ). The study was done on individuals with relapsing-remitting MS over a
period of 2 years. Then large-scale pharmacogenomic comparisons were done
between those who responded positively to the treatment and those who did not.
The researchers found that 18 of the 35 SNPs were signifi cantly associated with
positive interferon beta treatment response. Of these 18 mutations, 7 lie within
genes and the remainder are in non-coding regions. Many of the detected differ-
ences between responders and nonresponders were genes associated with ion chan-
nels and signal transduction pathways. The study also suggests that genetic variants
in heparan sulfate proteoglycan genes may be of clinical interest in multiple sclero-
sis as predictors of the response to therapy. Although additional research needs to be
done to further validate the study and understand the functional role of IFN-β, the
work has the potential to change the approach to MS treatment from a hit-and-miss
to a more systematic personalized management.
The BENEFIT (BEtaseron/Betaferon in Newly Emerging multiple sclerosis
for Initial Treatment) study incorporated pharmacogenetic and pharmacogenomic


12 Personalized Management of Neurological Disorders
Free download pdf