NYU neuroscientists have devised a method that has reduced several afflictions associated with Fragile X syndrome (FXS) in laboratory mice. Their findings, which were reported in the journal Neuron, offer new possibilities for addressing FXS, the leading inherited cause of autism and intellectual disability.
Those afflicted with FXS do not possess the protein FMRP, which is a suppressor of protein synthesis. Absent this suppressor, protein synthesis is exaggerated, producing a range of mental and physical disorders.
Previous research has indirectly targeted protein synthesis by seeking to temper, but not block, this process. The NYU researchers, by contrast, sought a more fundamental intervention—removing the enzyme S6K1, which has previously been shown to regulate protein synthesis in FXS mice. By addressing this phenomenon at the molecular level, they hoped to diminish many of the conditions associated with FXS.
To determine the impact of this intervention, the researchers compared the behaviors of these FXS mice with normal mice. Their results showed that protein synthesis in the FXS mice lacking S6K1 became similar to that of normal mice. Through a series of experiments and other measurements (e.g., navigating a maze, interacting with other mice), they found both physical and behavioral improvements in the FXS mice.
However, the researchers did not find uniform improvements in the tested FXS mice—they still engaged in excessive repetitive behaviors (i.e., repeatedly burying marbles in an experiment), a common trait among those afflicted with FXS. Nonetheless, the research team said the findings showed remarkable promise.
“We think these results set the stage for a viable pharmacological approach to target S6K1, with the aim of diminishing or even reversing the afflictions associated with Fragile X syndrome,” says Eric Klann, professor in NYU’s Center for Neural Science and the study’s senior author.
The study’s co-authors were Aditi Bhattacharya, Hanoch Kaphzan, Amanda Alvarez-Dieppa, and Jaclyn Murphy of NYU’s Center for Neural Science, and Philippe Pierre of Université de la Méditerranée in Marseille, France.
The research was supported by grants from the National Institutes of Health and the FRAXA Research Foundation.