More Research Required to Identify Distinctive Gene Expression Profile in Friedreich’s Ataxia

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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A study recently published in the journal The Cerebellum assessed the genetic expression of particular genes putatively related to Friedreich’s ataxia disease. The study is entitled “Gene Expression Profile in Peripheral Blood Cells of Friedreich Ataxia Patients” and was developed by researchers at Universidade Federal de São Paulo (UNIFESP) and Hospital Israelita Albert Einstein in Brazil.

Friedreich’s ataxia is a rare inherited neurodegenerative disease characterized by progressive damage of the nervous system with degeneration of the spinal cord and peripheral nerves that leads to muscle weakness, sensory loss, balance deficits and lack of voluntary coordination of muscle movements. Patients can also experience skeletal deformities, diabetes mellitus and hypertrophic cardiomyopathy (disorder in which the heart muscle becomes abnormally hypertrophied compromising its function). Friedreich’s ataxia is caused by a mutation in a gene called frataxin (FXN), which leads to a reduction in frataxin mRNA and protein levels in different tissues, including peripheral blood cells (PBC). Disease onset is usually during childhood or adolescence and the disorder leads to progressive disability, dependence on a wheelchair and reduced life expectancy. There is currently no therapy able to delay or reverse Friedreich’s ataxia disease progression.

Previous studies based on microarrays combined with real-time quantitative PCR, a method that allows the detection and measurement of the expression levels of a large numbers of genes, have shown that the decrease in FXN expression is linked to a complex gene expression profile, with several genes exhibiting an altered expression pattern, especially in pathways related to iron-sulfur metabolism and the inflammatory process.

The study of genes differentially expressed in PBC may provide a better understanding of Friedreich’s ataxia pathogenesis, and might potentially identify genes that could be used as reliable disease biomarkers.

In the study, researchers analyzed the expression of 26 specific genes that have been previously reported to be differentially expressed between Friedreich’s ataxia patients and healthy individuals. The team tested PBC from 11 Friedreich’s ataxia patients and 11 gender and age-matched healthy controls.

Researchers found that FXN was indeed strongly downregulated in PBC from Friedreich’s ataxia patients in comparison to healthy controls. However, apart from FXN, no other gene tested was found to have a statistically significant difference between Friedreich’s ataxia patients and controls.

The research team concluded that with the exception of the already known FXN gene, it was not possible to identify other genes that had a differential expression profile in PBC of Friedreich’s ataxia patients and healthy individuals. Further research is required to find a possible gene expression profile biomarker of the disorder.