Textbook of Personalized Medicine - Second Edition [2015]

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The methods selected are the considered to be most effective based on evidence
available so far. Cell therapy plays an important role in repair and regeneration.
Following recanalization of larger arteries by thrombolytic therapy, cell therapy can
target residual areas of ischemia due to small vessel atherosclerosis, reduce cell
death and facilitate neuronal plasticity as well as regeneration.
Hyperbaric oxygen (HBO), in addition to initial neuroprotection, also enhances
mobilization and action of intrinsic as well as transplanted stem cells (Jain 2009 ).
HBO is also an aid to rehabilitation of stroke patients. Response to HBO as transient
neurological improvement can also be used as an indication for revascularization
procedures such as extra-intracranial bypass operation.


Personalized Treatment of Multiple Sclerosis


Multiple sclerosis (MS) is a complex disease in which a substantial part of a person’s
liability to develop the disease is due to a combination of multiple genetic and non-
genetic risk factors. Genetic factors are considered to be responsible for the increased
frequency of the disease seen in the relatives of individuals affected with MS.
MS is considered to be an autoimmune disease associated with abnormalities in
immune regulation. Although etiology and pathogenesis of MS is still controversial,
a consistent feature of the pathology of the disease is entry of T cells into the CNS,
which induces an autoimmune infl ammatory reaction and initiates demyelination.
Immunomodulating agents have markedly improved treatment of MS because they
reduce the frequency and severity of relapses. Current therapies for MS include
interferon-β (IFN-β), glatiramer acetate, natalizumab and chemotherapy. These
therapies decrease the number of relapses and partially prevent disability accumula-
tion. However, their effi cacy is only moderate and they have adverse effects and that
are costly for health systems. The wide heterogeneity of MS as well as different
biological responses to immunomodulatory drugs can be expected to contribute to
differential treatment responses. Strategies that dissect the relationship between the
treatment response and the biological characteristics in individual patients are valu-
able not only as a clinical tool, but also in leading to a better understanding of the
disease. Examples of such approaches are:



  1. In vitro and ex vivo RNA expression profi les of MS patients under treatment
    with IFN-β have been determined by cDNA microarrays. Non-responders and
    responders to IFN-β as assessed by longitudinal gadolinium-enhanced MRI
    scans and clinical disease activity differ in their ex vivo gene expression profi les.
    These fi ndings will help to better elucidate the mechanism of action of IFN-β in
    relation to different disease patterns and eventually lead to optimized therapy.

  2. Spectratyping has shown that T cells receptors (TCRs) are activated in MS
    patients and Vbeta5.2 expansion is associated with the development of MS.
    T cell receptor (TCR)-based immunotherapy is feasible for MS patients if it is
    individualized according to TCR activation patterns of patients at different
    stages of the disease.


12 Personalized Management of Neurological Disorders
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