The first drug to treat the disorder Fragile X, instead of just its symptoms, showed some promise, according to a new study.

The drug, called AFQ056, helped improve symptoms in some patients, the researchers said in a statement released by Rush University Medical Center in Chicago. The patients who had the best response had a kind of fingerprint in their DNA, that could act as a marker to determine who should get treatment.

This is an exciting development. It is the first time we have a treatment targeted to the underlying disorder, as opposed to supportive treatment of the behavioral symptoms, in a developmental brain disorder causing intellectual disability, said study researcher Dr. Elizabeth Berry-Kravis, a pediatric neurologist and director of the Fragile X Clinic and Research Program at Rush. This drug could be a model for treatment of other disorders such as autism.

The drug is designed to block the activity of receptor found on brain cells, called mGluR5, that is involved in most aspects of normal brain function, including regulation of the strength of brain connections, a key process required for learning and memory.

How it works

People with Fragile X have a mutation in a single gene, nicknamed FMR1, and so they are missing a necessary brain protein. Normally, this protein acts as a brake on brain cell pathways activated by mGluR5. But patients with Fragile X are missing this protein, so mGluR5 pathways are overactive. This results in abnormal connections in the brain and the behavioral and cognitive impairments associated with Fragile X.

The research team found no significant effects of treatment when the entire group of 30 patients was analyzed. However, in a subsequent analysis, seven patients who had a a gene that was fully shut down -- presumably resulting in no FMR protein in the blood or brain -- showed significant improvement in behavior, hyperactivity and inappropriate speech with the treatment compared to placebo.

The treatment period in this pilot study was very short and longer treatment might have been needed to see improvement in the whole group of patients. Importantly, the drug was well-tolerated and there were no safety problems, said Berry-Kravis.

What lies ahead

A larger study of the drug is now underway that will recruit 160 patients worldwide and test the effects of a longer period of treatment. Rush University Medical Center is one of the participating sites.

Fragile X is the most common cause of inherited intellectual disability, the researchers said. The condition affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups. It is the most common known single gene cause of autism or autistic-like behaviors. Symptoms also can include characteristic physical and behavioral features and delays in speech and language development. The impairment can range from learning disabilities to more severe cognitive and intellectual disabilities.

The study was published in the January issue of Science Translational Medicine.