Molecule to reverse fragile X syndrome

A compound that shows promise in therapy for one of the diseases closely linked to fragile X syndrome, a genetic condition that is the only known single-gene cause of autism, has been developed.

Scientists at the Florida campus of The Scripps Research Institute focused on tremor ataxia syndrome, a disease related to fragile X syndrome that usually affects men over the age of 50 and results in Parkinson’s like-symptoms – trembling, balance problems, muscle rigidity, and some neurological problems, including short-term memory loss and severe mood swings.

For fragile X syndrome and related diseases, the primary problem is a structural motif called an “expanded triplet repeat” where a series of three nucleotides are repeated more times than normal in the genetic code of the affected individual . This defect – located on the fragile X mental retardation 1 gene (FMR1) - causes serious problems with the processing of RNA.

Study leader Matthew Disney, and colleagues have designed a compound that improves RNA splicing by stopping the repeat-associated defects in cell culture. At fairly high concentrations of the compound, the RNA defects were completely reversed. The findings are published in ACS Chemical Biology.

“While there is an abundance of potential RNA drug targets in disease, no one has any idea how to identify or design small molecules to target these RNAs. We have designed a compound capable of targeting the right RNA and reversing the defects that cause fragile x-associated tremor ataxia,” said Disney.

This study reinforces earlier work conducted by the team whose findings showed that it is possible to identify and develop small molecules that target RNA processing defects.

“Our approach is evolving into a general method that can be sued to target any disease that is associated with RNA, including, perhaps fragile X syndrome itself,” Disney added