Last updated August 14, 2018 at 3:07 pm
Study finds neuronal connections are undermined in FXS.
Stanford University researchers have identified a mechanism that alters the behaviour of neurons in Fragile X syndrome (FXS), an inherited genetic disorder that is the most common cause of inherited intellectual disability.
Their study also shows that targeting the mechanism could serve as the basis for new therapeutic interventions for FXS, which is currently difficult to treat.
FXS leads to severe intellectual disability and autistic-like behaviour. Screens for FXS are commonly included in prenatal genetic testing, and prospective parents with a family history of FXS are often referred to genetic counselling services. The condition has been tied to inactivation of a gene named FMR1.
In the latest study, Zhenjie Zhang and colleagues studied human neurons generated from induced pluripotent stem cells (iPSCs) taken from either control subjects or patients with FXS. They discovered that FMR1 inactivation in the FXS patient neurons impaired their neuronal plasticity – or their capacity to adapt and form new connections with other neurons.
Further analysis showed FMR1 inactivation inhibited signalling of retinoic acid (RA), a relative of vitamin A; RA deficiency was not observed in the neurons from the control group.
The authors were able to restore RA signalling in FXS cells by using a CRISPR engineering technique, suggesting that targeting RA deficiency could be a viable therapy for FXS patients. They also say iPSC-derived neurons are a useful resource for future studies that aim to investigate the mechanisms of FXS.
The paper is published in Science Translational Medicine.