Textbook of Personalized Medicine - Second Edition [2015]

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Personalized Management of Pain

Interindividual differences in the experience of pain have been appreciated clini-
cally for over a century. Essentials of personalized management of pain are shown
in Fig. 12.5.

Genetic Factors in Response to Pain

Gender, ethnicity, temperament and genetic factors also contribute to individual
variation in pain sensitivity and responses to analgesics. Pain measurement
scales can be used differently across individuals based on the past pain experiences
of individuals. The outcomes of clinical trials are based on the mean responses
of large numbers of subjects but fail to address inter-individual differences.

Table 12.7 Gene expression as biomarker of response to IFN-β in multiple sclerosis

Gene Protein Function Comments
CASP3 Caspase 3 Regulation
of apoptosis

Expression predicts response
to IFN-β
CAST Calpastatin Cell adhesion Response to IFN-β correlates
with gene polymorphisms
COL25 Collagen type XXV Extracellular
proteoglycans

Response to IFN-β correlates
with gene polymorphisms
FLIP FLIP Regulation
of apoptosis

Gene expression predicts
response to IFN-β
GPC5 Glypican 5 Ion channel regulation Response to IFN-β correlates
with gene polymorphisms
HAPLN1 Hyaluronan proteoglycan
link protein

Extracellular

proteoglycans

Response to IFN-β correlates
with gene polymorphisms
IAP-1,
IAP-2

IAP, IAP2 Inhibit caspase activation

and apoptosis

IFN-β reduces gene expression
in B lymphocytes
MMP-9 Matrix
metalloproteinase-9

Disruption of BBB,

immune cell migration

into the CNS, and

myelin degradation

IFN-β s uppresses MMP-9

mRNA

MX1 Myxovirus resistance
protein 1

IFN-β-induced protein

with an antiviral effect

MX1 is a biomarker of the
response to IFN-β
STAT JAK family of proteins Regulation of expression
of genes that mediate
biological effects of
INF-β

IFN-β activates JAK-STAT

signaling pathway

TRAIL TNF-related apoptosis-
inducing ligand

Regulation of apoptosis TRAIL expression is a marker

of IFN-β clinical effi cacy

© Jain PharmaBiotech

12 Personalized Management of Neurological Disorders