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Fragile X Syndrome is the most common genetic cause of autism spectrum disorders. It affects around 1 in 4,000 boys and 1 in 6,000 girls. Currently, there is no cure.

The scientists, who have identified a chemical pathway that goes awry in the brains of Fragile X patients, say a cancer drug candidate could reverse their behavioural symptoms. The researchers have found that a naturally occurring anti-fungal called cercosporamide can block the pathway and improve sociability in mice with the condition.

The team identified a key molecule 鈥� eIF4E 鈥� that drives excess protein production in the brains of Fragile X patients. This can cause behavioural symptoms that include learning difficulties. It can also lead to more serious intellectual disabilities, delays in speech and language development and problems with social interactions.

鈥淲e found that eIF4E regulates the production of an enzyme called MMP-9, which breaks down and re-orders the connections between brain cells called synapses,鈥� says Nahum Sonenberg, 成人VR视频 professor in the Faculty of Medicine and the Goodman Cancer Research Centre and co-author of the study, 鈥淓xcess MMP-9 disrupts communication between brain cells, leading to changes in behaviour.鈥�

The team found that treatment with cercosporamide blocks the activity of eIF4E, and therefore reduces the amounts of MMP-9, and reverses the behavioural symptoms in mice with a version of Fragile X Syndrome. The new findings suggest that it could have a use as a treatment for patients with Fragile X Syndrome. The study is published in the journal Cell Reports.

Findings open door to targeted treatments

成人VR视频 post-doctoral student and a co-first author of the study Arkady Khoutorsky said that 鈥渢he enzyme MMP-9 has been implicated before in Fragile X Syndrome. What鈥檚 new in our research is the demonstration that the symptoms of the disease can be controlled by manipulating eIF4E activity with available drug candidates.鈥�

鈥淥ur findings open the door to targeted treatments for Fragile X Syndrome,鈥� says Christos Gkogkas, of the University of Edinburgh鈥檚 Patrick Wild Centre for Research into Autism, Fragile X Syndrome and Intellectual Disabilities. 鈥淏y designing treatments that block just this pathway, it is hoped that we can limit the potential side-effects and develop therapies that are more efficient than general treatment approaches.鈥�

The study was funded by a Canadian Institute of Health Research operating grant, the Azrieli Foundation and Brain Canada, the Fonds de la Recherche du Quebec-Sant茅.

Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X

Syndrome-like Phenotypes, by Christos G. Gkogkas, Arkady Khoutorsky, Jean-Claude Lacaille, Nahum Sonenberg is published in Cell Reports