New research, published online in the journal Proceedings of the National Academy of Sciences last week, shows that blocking the activity of a gene in the brain - which regulates the enzyme p21-activated kinase (PAK) - can reverse symptoms of mental retardation and autism in mice with Fragile X syndrome (FXS).
The research, carried out at the US Picower Institute of the Massachusetts Institute of Technology, could potentially lead to the development of a drug which targets the human equivalent of the gene, raising the prospect of a treatment for autism and mental retardation in the future.
'Our study suggests that inhibiting a certain enzyme in the brain could be an effective therapy for countering the debilitating symptoms of FXS in children, and possibly in autistic kids as well', said co-author Mansuo Hayashi, a former Picower Institute postdoctoral fellow currently at Merek Research Laboratories in Boston.
FXS is caused by a mutation in the X chromosome's FMR1 gene. Brain abnormalities in these patients result in a weakening of the electrical signals sent along so-called dendric spines - connections involved in communication between brain cells - which become abnormally longer, thinner and more abundant.
The researchers bred genetically altered mice which exhibited symptoms similar to those of FXS patients, such as repetitive movements and learning difficulties. They programmed the PAK gene in these mice to switch off a few weeks after the FXS symptoms first appeared.
When PAK activity was blocked, the FXS symptoms were reversed in the mice. Furthermore, closer inspection of the mouse brains revealed that the brain abnormalities were also reversed, producing shorter, fatter and less numerous spines, more closely resembling those in normal mice.
'Strikingly, PAK inhibition also restored electrical communication between neurones in the brains of the FXS mice, correcting their behavioural abnormalities in the process', said co-author Susumu Tonedawa, Nobel laureate and Picower Professor of Biology and Neuroscience.
The fact that PAK inhibition reversed abnormalities after symptoms emerged is 'very exciting', commented Eric Klann, a professor at New York University's Centre for Neuroscience, who was independent of the study. 'It suggests that PAK inhibitors could be used for therapeutic purposes to reverse already established mental impairments in fragile X children', he added.
There is currently no effective treatment for FXS, yet it is the most common inherited cause of learning difficulties. According to figures from the US Centres for Disease Control (CDC), the disease affects 1 in 4000 men and 1 in 6000 women worldwide.
Dr Michael Tranfaglia, Medical Director of the Fragile X Research Foundation, which helped to fund the study, is optimistic about the potential for future treatments: 'Many other developmental disorders share the dendritic abnormalities which are rescued by PAK inhibition, so this may be an effective strategy for treating conditions like autism', he says.