Among the various genetic intellectual diseases followed up by the teams at the Jérôme Lejeune Institute, Fragile-X Syndrome occupies an important place. Affecting one new-born baby out of 4000, no treatment has been found for this syndrome to this day. But, lately, research has aroused a new hope.
Fragile-X Syndrome is a genetic disease which leads to an intellectual disability often associated with autistic behavioural disorders and recognisable physical signs, such as a narrow, oval face, protuberant ears and forehead, abnormally supple fingers and flat feet. Intellectual problems are variable as are also the behavioural disorders which can be anything from mild to very serious autistic disorders. It is precisely these behavioural disorders that Doctor Sylvain Briault’s teams from the INEM laboratory (CNRS- University of Orléans: experimental and molecular immunology and neurogenetics laboratory) have been fighting. This laboratory has already been funded by the Foundation for its work on Fragile-X.
Indeed, previews research has put in evidence that, in the case of Fragile-X Syndrome, the activity of the potassium channel BKCa is perturbed. This channel, essential for the good functioning of the cells as it enables the ions to pass into the cells, is functional in patients living with Fragile-X but is only half as operational as it is for healthy subjects. BKCa has therefore been identified by researchers as a new potential therapeutic target.
The team then tested a molecule called BMS 204352, capable of opening this channel to compensate for the missing ones. The promising results obtained in vitro have led the researchers to pursue the trials in vivo, on mouse models for Fragile-X Syndrome. They noticed that the molecule opened the existing potassium channel very largely, and considerably increases its activity, making it equivalent to the witnesses. Thus, the behaviour – on a cognitive, emotional, and social level- of the mouse models for Fragile-X Syndrome became similar to the wild mice used as witnesses for this study.
The use of this molecule for the treatment of Fragile-X Syndrome has been patented several times by the CNRS, the University of Orléans and the regional hospital centre of Orléans. In November, the European Health Authorities granted the status of orphan drug to the molecule BMS 204352. Thanks to the support of the Agence pour la Santé Européènne (European health agency), Dr Briault’s team will be able to make significant advances in its research. The results of this study are very promising and offer new prospects, even if it is obvious that caution is the key word as the clinical trial has not been carried out yet. This is therefore a new interesting lead to be explored, with as a possible outcome, the development of a treatment for fragile-x.