Rett syndrome (RTT) is a severe postnatal
neurological disorder caused by mutations in the
methyl-CpG binding protein 2 (MECP2) gene. In affected children, most
biological parameters, including brain structure, are normal (although acquired
microcephaly is usually present). However, in recent years, a deficit in bioaminergic metabolism has been identified at the cellular and molecular levels, in more than 200 patients. Recently available transgenic mouse strains with a defective Mecp2 gene also show abnormalities, strongly suggesting that there is a direct link between the function of the
MECP2 protein and the metabolism of
biogenic amines.
Biogenic amines appear to have an important role in the pathophysiology of
Rett syndrome, for several reasons. Firstly,
biogenic amines modulate a large number of autonomic and cognitive functions. Secondly, many of these functions are affected in RTT patients. Thirdly,
biogenic amines are the only
neurotransmitters that have repeatedly been found to be altered in RTT patients. Importantly, pharmacological interventions can be envisaged to try to counteract the deficits observed. Here, we review the available human and mouse data and present how they have been and could be used in the development of pharmacological treatments for children affected by the syndrome. Given our current knowledge and the tools available, modulating
biogenic amine metabolism may prove to be the most promising strategy for improving the life quality of
Rett syndrome patients in the short term.