Reference:
2
Abstract:
In a recent study, we have reported that the administration of a toxin derived from bacteria, for brevity called CNF1, improved in a clear manner some of the behavioral alterations observed in transgenic mice, a model for Rett syndrome. CNF1 The result is also able to counteract some morphological abnormalities in the brains of these mice, restoring a condition at all comparable to the control animals. On the basis of these results, which provide an important first demonstration of the beneficial effects of CNF1, we set ourselves the goal of deepening the potential therapeutic value, providing additional evidence that they are able to suffragarne the effectiveness and trying to clarify the mechanism action of CNF1 on the nervous system. For this purpose, detailed behavioral analysis will be conducted in two mouse models, which differ in the severity of symptoms, focused to identify the most sensitive aspects to treatment with CNF1, and also characterizing the temporal progression. We have already described the role of astrocytes, a large population of non-neuronal cells of the brain, which is a significant contributor to the dysfunction underlying the syndrome and that seems to represent an important target of the action of CNF1 in the brain. As part of the ongoing project then we will try to further clarify the contribution of astrocyte dysfunction in the pathogenesis of Rett and its modification by the CNF1. To increase the value of translational analysis of the symptoms and effects of the proposed treatment will be examined in subjects of both sexes. In the evaluation of the project is scheduled routes of administration of CNF1 devices, alternative direct inoculation in the brain, which is currently unavoidable given the size of the protein CNF1. Given the extreme complexity of the clinical picture and the absence of targeted therapies, although only partial effects of CNF1 on Rett symptoms would be highly relevant. Also, since the CNF1 exerts its action by modulating the cellular level, the family of RhoGTPasi, extensively involved in the phenomena of plasticity, the evidence of possible therapeutic effects of CNF1 could be extended to other syndromes, neurodevelopmental disorders.
PROJECT DETAILS
beginning: 2012.
end: 2013.
Country of research: Italy
Counry of funding source: Italy
Funding organization: AIRETT
Financing: PRIVATE FUNDERS – 100 000 €