Early intervention with psychostimulants or antidepressants to increase methyl-CpG-binding protein 2 (MeCP2) expressions: a potential therapy for Rett syndrome.
Rett syndrome (RTT) is a severe X-linked postnatal neurodevelopmental disorder. The syndrome is caused primarily by mutations in the methyl CpG binding protein 2 (MeCP2) gene on Xq28. Most individuals with RTT are female, and female RTT is normally heterozygous for mutations in MeCP2. Patients with RTT display a normal period of development prior to the onset of symptoms, at which point they undergo a period of regression. Currently, no effective medication is available for this disorder, although animal studies have suggested that RTT symptoms are potentially reversible. For females with RTT, the severity of symptoms and progression of the disease varies a great deal, despite its homogenous genetic origin. These differences could be attributed to differences in the mutation points of MeCP2 and the skew caused by X-chromosome inactivation. Thus, the increased expression in the normal MeCP2 gene could decrease the severity of the disease. Based on findings from studies on animals indicating that fluoxetine (an antidepressant) and cocaine (a psychostimulant) can increase MeCP2 expression in the brain, it is suggested that early intervention with antidepressants or psychostimulants could increase the normal MeCP2 expression in females with RTT, who are normally heterozygous. This therapeutic hypothesis could be tested in an RTT animal model. Following the identification of the antidepressants or psychostimulants with the greatest influence on MeCP2 expression, a combination of early detection of the disorder with early intervention may result in improved therapeutic outcomes. Furthermore, a trial investigating the effects of antidepressants or psychostimulants on MeCP2 expression in lymphocyte culture from patients with RTT is suggested for clinical therapeutic prediction.
Department of Psychiatry, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Chia-Ho
CH
Pan
Shihjen
S
Tsai
D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D061345:Early Medical Intervention; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D008954:Models, Biological; D015518:Rett Syndrome / Q000188:drug therapy*; D049951:X Chromosome Inactivation / Q000502:physiology
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D005473:Fluoxetine; D003042:Cocaine