Intractable Rare Dis Res. 2014;3(4):100. (DOI: 10.5582/irdr.2014.01033)
Translational research guided by animal studies in Fragile X Disorders.
Hagerman R, Lozano R, Schneider A
This special issue on fragile X-associated disorders will open your eyes to the broad spectrum of clinical involvement that occurs with mutations in the FMR1 gene. This gene creates a protein, FMRP, which is a key protein for regulating the translation of hundreds of mRNAs, particularly those involved in synapse formation and plasticity. Fragile X syndrome (FXS) results from the loss or deficiency of FMRP and it is the most common cause of inherited intellectual disability and autism or autism spectrum disorder (ASD). The review of animal models for FXS by Kazdoba-Leach et al. (2014) demonstrates how these models have led the way to targeted treatments for FXS and for ASD. One of the more promising new treatments for FXS is the use of low dose sertraline in young children 2 years and older with FXS. The paper by Hansen and Hagerman (in this edition) outlines the benefits of sertraline including the enhancement of serotonin neurotransmission, neurogenesis, and BDNF levels that has the potential to improve language and development for these children. GABA agonists and mGluR5 antagonists have also been studied in FXS but the mouse model is easily rescued with many different targeted treatments, whereas the patients with FXS have only responded well to a few new treatments. There is a great need to improve the participation of minorities in the new clinical trials of targeted treatments for FXS and this is reviewed in detail by Chechi et al. (2014) in this issue.