Reactivation of FMR1 gene expression is a promising strategy for fragile X syndrome therapy.

08:00 EDT 12th March 2020 | BioPortfolio

Summary of "Reactivation of FMR1 gene expression is a promising strategy for fragile X syndrome therapy."

Fragile X syndrome (FXS) is the most common form of intellectual disability and autism spectrum disorder and is caused by CGG repeat expansion in the promoter region of the FMR1 gene, which encodes fragile X mental retardation protein. This event leads to gene silencing and the loss of gene products through DNA methylation and chromatin remodeling. Due to the pathogenesis of FXS, targeted, symptomatic, and etiological approaches have been developed for its treatment. Despite their rapid development, symptomatic and targeted treatment approaches have numerous limitations; etiological approaches have the greatest potential because they affect the main causes of transcriptional silencing. In this review, we consider three potential etiological therapeutic methods that affect the reactivation of FMR1 gene expression: treatment with inhibitors of chromatin-modifying enzymes, the use of noncoding RNAs and the application of gene therapy. Inhibitors of chromatin-modifying enzymes are not clinically applicable because of their low reactivity and high cytotoxicity, and noncoding RNAs are currently only under study. Thus, we discuss gene therapy as the most promising approach for treating FXS in the near future.


Journal Details

This article was published in the following journal.

Name: Gene therapy
ISSN: 1476-5462


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Medical and Biotech [MESH] Definitions

Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)

A RNA-binding protein that is found predominately in the CYTOPLASM. It helps regulate GENETIC TRANSLATION in NEURONS and is absent or under-expressed in FRAGILE X SYNDROME.

An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.

The expression of a gene in an abnormal place, or at an abnormal time in an organism. Ectopic Gene Expression is often induced artificially by genetic techniques.

A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.

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