The first drug to treat the cause of inherited intellectual disability

ScienceDaily: promising results have emerged from the first drug to target the causes of fragile X syndrome, rather than just easing its symptoms. They were published in the January 2011 issue of Science Translational Medicine, and the researchers at Rush University Medical Center involved in the study are running longer clinical trials.

Fragile X syndrome is the most common inherited cause of intellectual disability, accounting for about 10% of intellectual disability worldwide.

The published data covered 30 patients with fragile X syndrome who were given an experimental Novartis drug known as AFQ056. The drug improved clinical symptoms in some patients, and those who benefited most had a particular genetic marker, which means a DNA test could show whether the drug will work.

The researchers, excited by the results, say this is the first time a treatment has targeted the root of the problem, instead of helping patients cope with symptoms and offering behavioural therapies for a brain whose development was delayed. The drug may also be important for treating autism.

The drug is designed to block a brain receptor called mGluR5, which is involved in most brain activity, including forming proper connections between nerve cells, essential for memory and learning. In fragile X syndrome, an important protein called FMRP loses its ability to keep mGluR5 in check and so to regulate nerve connections. Without this regulating protein, connections become random and sparse, causing intellectual, behavioural and language difficulties.

The Swiss researchers said the drug did not appear to have important side effects in the 30 patients, and seven of them showed improvements in behaviour and control of hyperactivity and speech.

The study was short, and the drug may need longer treatment to show clearer results. What matters is that it is well tolerated and there are no safety concerns. Further trials with 160 patients around the world over a longer period are planned.

About one in 4,000 males and one in 6,000 females worldwide, of all ethnic groups, have the condition. Its signs include autistic behaviour, physical and psychological features, and delayed physical and language development, ranging from learning difficulties to severe intellectual disability.