Glatiramer acetate (GA, Copolymer-1) an hypothetical treatment option for Rett syndrome.

Abstract:

:Rett syndrome (RTT) is an X-linked dominant postnatal severe and disabling neurodevelopmental disorder which is the second most common cause for genetic mental retardation in girls and the first pervasive disorder with a known genetic basis. The syndrome is primarily caused by mutations in the Methyl CpG binding protein 2 (MECP2) gene on Xq28. Its protein product MeCP2 acts as a transcriptional repressor or activator depending on the target gene associated. Brain derived neurotrophic factor (BDNF) is a neurotrophic factor playing a major role in neuronal survival, neurogenesis and plasticity. It has been identified as a major MeCP2 target through a candidate gene approach and abnormalities in BDNF homeostasis are believed to contribute to the neurologic phenotype and pato-physiology of part of the symptoms in Mecp2 null mice that show progressive deficits in its expression. Based on the presumed role of BDNF in the pathophysiology of Rett syndrome it is reasonable to assume that interventions that will elevate its levels in the brain of RTT patients will be of therapeutic benefit. Glatiramer acetate (GA, Copolymer 1, Copaxone) an immunomodulator with proven safety and efficacy in Multiple Sclerosis has been reported to cause elevated secretion of BDNF both in animal model and in MS patients. Our hypothesis is that continuous treatment of patients with RTT with Glatiramer acetate might lead to an increase in their brain's BDNF content and an improvement in at least part of the syndrome symptomatology while being safe to use and well tolerated in this population. In a pilot preliminary study we have shown that GA cause elevation of BDNF expression up to the level in naïve control mice in several cortical areas in the Mecp2 mutated mouse brain, but as of yet did not examine the behavioral aspects of this elevation.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

Ben-Zeev B,Aharoni R,Nissenkorn A,Arnon R

doi

10.1016/j.mehy.2010.09.015

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

190-3

issue

2

eissn

0306-9877

issn

1532-2777

pii

S0306-9877(10)00369-5

journal_volume

76

pub_type

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