Tratamientos actuales para el Síndrome de Duplicación de MECP2

Methyl-CpG-binding protein 2 (MeCP2) is a small, intrinsically disordered protein which has a role in gene activation and repression, and chromatin compaction. When MECP2 gene, located in the X chromosome, suffers a duplication, MeCP2 expression increases, leading to the outbreak of seizures, hypotonia, autistic features and respiratory infections. This disorder is known as MECP2 Duplication Syndrome (M2DS).The aim of this Master’s thesis is to gather all the existing drug trials and auxiliar treatments for M2DS.The search returned 10 cases of drug trials (6 performed on humans, 1 on human iPSCs and 3 on M2DS mouse models). Anticonvulsants are the most frequently prescribed drugs on young patients, although antisense oligonucleotides (ASOs) and CRISPR-Cas9 gene editing are being developed in preclinic studies. The main auxiliar therapies found for M2DS were occupational, physical and speech therapy.Valproic acid (VPA) is the most used anticonvulsant for the treatment of seizures in children with M2DS, but other drugs have also proven to be effective, such as lamotrigine (LTG) and topiramate (TPM). The screening of small compounds able to destabilize the MeCP2-DNA union could also be a fruitful source of long-term drugs against M2DS. Auxiliar therapies will continue to be imperative until a full phenotype reversal can be achieved in human patients via gene editing.