Demyelinating Autoimmune Diseases, CNS Clinical Trial
Official title:
Epigenetic Evaluation of HAT/HDAC Activity in Peripheral Blood Mononuclear Cells From Patients With Clinically Isolated Syndrome and Analysis of the Relationship With the Pathophysiology and Disease Activity
The aim of the study is to compare the enzymatic activity of HATs and HDACs in peripheral blood mononuclear cell (PBMC) of patients with a clinically isolated syndrome (CIS group) and healthy controls (control group).
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central
nervous system (CNS). Clinically isolated syndrome (CIS) is often a sign of multiple
sclerosis and the term refers to the first episode of neurologic symptoms experienced by a
patient. Possible presentations of CIS include optic neuritis, a brain stem and/or cerebellar
syndrome, a spinal cord syndrome, or occasionally cerebral hemispheric dysfunction. An
accurate diagnosis at this time is important because people with a high risk of developing MS
are encouraged to begin treatment in order to delay or prevent a second neurologic episode
and, therefore, the onset of MS.
The innate and adaptative immune systems play an important role in pathophysiology of MS,
acting in interaction with environmental, genetic, and epigenetic factors.
Epigenetic modifications, such as DNA methylation and histone modification, alter DNA
accessibility and chromatin structure, thereby regulating patterns of gene expression. These
processes are crucial to normal development and differentiation of distinct cell lineages in
the adult organism. Histone acetylation, through the family of histone acetyl transferase
(HAT), is most consistently associated with promoting transcription. Deacetylation of
histones correlates with CpG methylation and the inactive state of chromatin. There are 4
classes of histone deacetylase enzymes (HDACs), with members capable of deacetylation of
histones and/or other protein targets. Acetylation homeostasis is a key regulator of both
immune cell activation. Of note, potent histone deacetylase inhibitors (HDACi) endowed with
antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in
experimental models of MS has been reported consistently. This study could provide
information on the mechanisms involved.
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