Expanded GAA repeats in the FXN gene trigger a series of changes that switch the gene off, preventing cells from producing enough frataxin. While scientists have long known that these repeats cause FXN silencing, the molecular mechanisms that recognize the mutation and initiate this process remain poorly understood.
Recent research has identified proteins that appear to recognize the expanded GAA repeats and trigger the molecular events that silence the FXN gene. This project will investigate whether these proteins are responsible for initiating FXN gene silencing in patient-derived cells and determine how they contribute to the loss of frataxin production.
The researchers will also explore strategies to block this detection and silencing mechanism. If successful, this work could identify a new therapeutic approach for restoring frataxin production and provide an important step toward the development of treatments for people living with Friedreich’s ataxia.