In 90% the severe genetic form of mental retardation is caused by a mutation in the gene MECP2, revealed now other biochemical processes that will be new drug targets.
From research telethon a possible new weapon against the Rett syndrome, a serious neurological disease of genetic origin is still no cure: to describe in the journal Human Molecular Genetics is a multidisciplinary team coordinated by Maurizio Giustetto University of Turin and the National Neuroscience and Vania Broccoli University Scientific Institute San Raffaele in Milan.
Rett Syndrome
Rare and widespread only among females, Rett syndrome is a disease still somewhat mysterious to scientists: the knowledge that in 90% of cases the cause is a defect in the gene MECP2, is not yet clear how this DNA damage is translates into serious symptoms of the disease. Completely normal at birth, around one year of age these children begin to lose it in an irreversible way the skills acquired in language, movement and relationship with the outside world. “It’s like their brains remain” frozen “in an immature and a certain point in time no longer able to keep pace with the development of the rest of the body,” says Maurizio Giustetto.
“This is not a neurodegenerative disease in which nerve cells are progressively destroyed, as is the case in AD or Huntington’s disease. In Rett syndrome the problem seems to originate in the inability of the synapses, contacts between a neuron to another, to exchange information correctly nerve. We have therefore tried to understand why this unusual and, in the long run, harmful “dialogue” neuronal “.
Thanks to multidisciplinary skills, researchers have studied a particular Telethon pathway already known to be involved in other forms of mental retardation: coordinated by the mTOR protein, this group of “molecular actors is essential for the synthesis of proteins in nerve cells and the correct formation and functioning of synapses. By studying the animal model of Rett syndrome, Giustetto and colleagues discovered that the defect in the MECP2 gene that interferes with its metabolic pathway, resulting in particular the alteration of a protein called rpS6. “Clarifying the molecular details of genetic disease is not an exercise in style, but the only way to discover possible therapeutic strategies,” said Giustetto yet. “We know that there are drugs already in use in clinical trials for other neurological diseases, capable of penetrating the brain and modulate the activity of certain proteins in the pathway that we studied, such as rpS6. This means that in times reasonable to think we could test them on our patients, hoping to at least partially control the symptoms. ”
We must remember that fact when there is no treatment for Rett syndrome. “Please correct the genetic defect with gene therapy, as Telethon has already done or are trying to do for other diseases, it is particularly difficult in this case,” said Vania Broccoli. In all those women, who have two X sex chromosomes of type, each cell “turns off” one of these chromosomes: the girls with Rett syndrome are thus a mosaic, because they have some cells with the chromosome containing the genetic defect ” on “, in a variable percentage of cases at home and in proportion to the severity of symptoms. “If gene therapy is a goal far away in the near future is not possible to suggest drug therapies, perhaps in combination, can interfere with the mechanisms of altered brought to light thanks to basic research and thus undermine the vicious circle is established in the brains of these children. Get well get in touch with the world around them. ”
The study took part in other research groups funded by Italian Telethon, including that of Thomas Pizzorusso Institute of Neurosciences of the CNR of Pisa and the University of Florence, Nicoletta Landsberger and Stefano Biffo University Scientific Institute San Raffaele Milan.
