EPIGENETIC APPROACH IN THE TREATMENT OF FRAGILE X SYNDROME: INTEGRATIVE REVIEW.

Abstract

In fragile X syndrome (SXF), the loss of expression of the FMR1 gene is caused by unstable expansion of the repetition (CGG)n in the 5 'untranslated region. To date, there is no pharmacological treatment directed to the etiopathogenesis instituted. With the advances in epigenetics, there is evidence of new target-specific therapeutic approaches in cells of carrier patients. The aim of the study was to investigate the content of publications on epigenetic therapies for SXF. An integrative review was carried out in the PubMed, BVS and EMBASE databases, using the descriptors: “DNA demethylation” OR “Histone deacetylase inhibitor” OR “Histone acetylation” OR “Epigenetic treatment” AND “Fragile X syndrome”. From the search, 172 heterogeneous articles were found, of which 22 were selected, according to the established exclusion criteria. Among the drugs tested for transcriptional reactivation, histone deacetylase inhibitors (HDAC) and DNA methyltransferase inhibitors (DNMT) are highlighted, the main ones being evaluated for 5-aza-2-deoxycytidine (5-azadC), 5- azadesoxycytidine and TSA. 5-azadC was the most studied, presenting promising results in relation to the reactivation of FMR1, with restoration of expression between 8% and 70% in relation to the levels found in cells of normal individuals, the dose of the substance being closely linked to its effectiveness . However, the higher the dose of 5-azadC, the greater the toxicity, limiting its therapeutic use. The present study demonstrated that there is still little research in the field of epigenetic therapy, therefore, new compounds must be investigated in order to find an efficient and safe drug for SXF.