The article explains that Fragile X and autism may present differently, with autism showing a broader range of repetitive behaviors or restricted interests. The leading theory for the cause of Fragile X syndrome is synaptic dysfunction, which involves disruptions in protein synthesis.
The prevalence of Fragile X ‘premutation’, defined as having 55 to 200 CGG repeats in the FMR1 gene, is unknown as carriers may not exhibit outward signs. Estimates suggest that 1 in 148 to 1 in 291 women and 1 in 290 to 1 in 855 men in the US have premutations. Some women with premutation develop fragile X-associated primary ovarian insufficiency, triggering early menopause, while both men and women may develop fragile X-associated tremor/ataxia syndrome, which causes tremors and cognitive problems.
Mouse and rat models of Fragile X syndrome have been developed by deleting the FMR1 gene. These models show abnormal responses to social stimuli and alterations in the prefrontal cortex, which is involved in social cognition. However, the applicability of insights from these models to humans with Fragile X syndrome remains uncertain, as behaviors in FMR1-deficient mice often differ from those in humans.
Currently, there are no approved drugs for treating Fragile X syndrome. However, several candidate drugs, such as arbaclofen and mavoglurant, have shown promise in restoring protein production and improving learning and memory in mutant mice. Clinical trials for these drugs have not been successful, possibly due to inappropriate markers of effectiveness or limited response in older individuals. Researchers are now testing mavoglurant in young children with fragile X syndrome, paired with intensive language intervention. Lovastatin, a cholesterol-lowering drug, is also being tested for its ability to reduce seizures in fragile X mice, and another drug targeting the enzyme PDE4D shows potential in improving social behaviors in mutant mice.
Future steps in the field include developing reliable outcome measures for clinical trials and investigating promising drug candidates. Researchers are focused on developing outcome measures and understanding the functions of FMRP to repair the mutation associated with Fragile X syndrome. In a recent study, researchers successfully used gene-editing to remove CGG repeats in cells from a person with Fragile X, leading to restored FMRP expression at 90% of normal levels.
Overall, this article highlights the latest developments in autism research, specifically regarding Fragile X syndrome’s link to autism and potential treatment options.
