LIMK1 inhibitors - A novel, disease-modifying approach for the treatment of fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited cause of learning disabilities and it affects around 1 in 5000 individuals (more common in males than females), and boys with FXS generally have more pronounced clinical symptoms than girls. It is characterised by learning difficulties, autism, behavioural challenges and social, emotional, attention and language problems as well as the potential to develop epilepsy. The clinical symptoms appear in early childhood and last into adulthood by which time the majority of FXS patients have also developed an anxiety disorder. FXS is caused by a change in a single gene (the FMR1 gene) which alters production of a protein called FMRP. This protein is important in controlling the proper connection between nerve cells in the brain, allowing them to communicate effectively. This change in the FMR1 gene prevents production of the FMRP protein and leads to changes in the brain that result in the signs, behaviours and symptoms of FXS. Recent discoveries from several labs have uncovered key findings of the link between the loss of the FMRP protein and the changes that occur in the brain. Of particular interest has been the discovery of another protein, LIMK1, which acts as a master regulator and which is over-active in FXS individuals. Our approach is to design drug molecules which can inhibit this master regulator protein, and by doing so, reverse the impact of the loss of the FMRP protein. There are no currently approved drugs for FXS. Therefore, we believe this approach has a realistic chance to deliver a unique and transformative therapeutic agent for individuals with Fragile X.