A remarkable new tool in the world of genetic biology is being applied to study Friedreich’s ataxia. TALEN and CRISPR methodologies, which have been the subjects of recent patent battles, are powerful gene modifying techniques that can easily add or remove sequences to mimic the mutations that occur in Friedreich’s ataxia. Using these technologies, two laboratories in MRC National Institute for Medical Research and Kings College London created a new cellular model that provides a platform to study Friedreich’s ataxia disease progression.
“Using these tools, we obtained what may be a powerful tool to follow the progression of Friedreich’s ataxia, which may finally allow us to understand the molecular basis of this disease,” wrote Dr. Tommaso Vannocci, lead author of a study published by the group. “The model will allow us to quantify the effects of reduced levels of frataxin in a time-controlled way.”
As explained in the article, “A New Cellular Model to Follow Friereich’s Ataxia Development in a Time-Resolved Way,” which was published in Disease Models & Mechanisms, the researchers’ approach to model the disease is unique from other groups’ attempts to study the effects of frataxin depletion. In previous studies, generating cells from Friedreich’s ataxia patients or one-time inducible genetic defect mice did not allow time-based data to be collected when studying disease progression.
As a first step, the researchers generated a cell line that was deficient in the protein frataxin. A variety of methods were tested, but the researchers ultimately selected CRISPR due to the higher efficiency and reproducibility of results. The majority of experiments conducted were to characterize the genetic material of the affected cell lines. Next steps include using cells obtained from Friedreich’s ataxia patients that are de-differentiated into induced pluripotent stem cells to then generate neurons and cardiac cells, as Friedreich’s ataxia generally manifests in these cell types.
“We are thus now in a strong position to follow and understand the early stages in the development of Friedreich’s ataxia,” wrote the authors. They believe the work will provide a platform to be used in studying and diagnosing Friedreich’s ataxia.