Textbook of Personalized Medicine - Second Edition [2015]

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ATP1A2, encoding a catalytic subunit of a sodium-potassium-ATPase, have been
found in some families with dominantly inherited hemiplegic migraine. These two
genes are not associated with more common migraine syndromes and are not the
most common hemiplegic migraine genes. However, the work on migraine can also
have implications for the increasing number of additional neurological episodic dis-
orders with the common denominator of channelopathy. Genome-wide analysis of
a large population in Europe, including migraineurs and non-migraineurs, revealed
that two SNPs, rs2651899 and rs10166942, were associated with migraine, but the
association was not preferential for migraine with aura or without aura, or with any
for specifi c features of migraine (Chasman et al. 2011 ).


Individualization of Use of Triptans for Migraine


With a large number of triptans now available, it may be possible to match indi-
vidual patient needs with the specifi c characteristics of the individual triptans to
optimize therapeutic benefi t. Pharmacogenetics provides the possibility of tailoring
the therapeutic approach to individual patients, in order to maximize treatment effi -
cacy while minimizing the potential for unwanted side-effects (Buzzi 2008 ). Pain
relief by triptans is signifi cantly modulated by a common genetic variant − G protein
beta3 (Schürks et al. 2007 ). Genetic profi ling of predisposition to migraine should
facilitate the development of more effective diagnostic and therapeutic applications.
Pharmacogenomics will most likely provide a stronger scientifi c basis for optimiz-
ing triptan therapy on the basis of each patient’s genetic constitution (Tfelt-Hansen
and Brøsen 2008 ; Tfelt-Hansen 2009 ).
Pharmacogenomics may help in rationalizing triptan administration according to
characterization of an individual’s genomic profi le. An observational study shows
that serotonin transporter gene polymorphism STin2 VNTR confers an increased
risk of inconsistent response to triptans in migraine patients (Terrazzino et al. 2010 ).
Although some genetic factors infl uence drug response, prediction of therapy
response with adequate predictive power requires a systematic approach to genetic
association studies due to complexity of the fi eld (Gentile et al. 2011 ).


Multitarget Therapeutics for Personalized Treatment


of Headache


Migraine is a special type of headache. For most headaches in practice, genotyping
is impractical and unnecessary. Different aspects of pain perception, i.e. sensory and
affective components, also explain why there is not just one single target structure
for therapeutic approaches to headache. A network of brain areas is involved in pain
perception and pain control. This diversifi cation of the pain system explains why a
wide range of molecularly different substances can be used in the treatment of


12 Personalized Management of Neurological Disorders
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