Chronic Inflammatory State Linked to Friedreich’s Ataxia, Genetic Study Reveals

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by Alice Melão |

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Friedreich’s ataxia is associated with a chronic inflammatory state, according to the genetic pattern of peripheral blood cells revealed in a research study.

The UCLA study is titled “Peripheral blood gene expression reveals an inflammatory transcriptomic signature in Friedreich’s ataxia patients,” and is published in the journal Human Molecular Genetics.

Friedreich’s ataxia is characterized by several cellular changes that are triggered by the loss of functional frataxin protein. This includes an alteration of gene activity levels in tissues that are most affected by the disease, such as sensory nerve cells and brain cells.

Although this is valuable information to better understand the underlying processes that mediate the disease, these cells are not easily accessible and so cannot be used to diagnose and evaluate disease status.

All the cellular stress and eventual cell loss in the nervous system may also trigger peripheral immune responses that have not been fully addressed.

To shed light on this matter, a team led by researchers at University of California Los Angeles analyzed the genetic pattern of blood cells in patients with Friedreich’s ataxia.

They evaluated blood samples collected from 418 patients and compared them to those of 228 people who were carriers of FXN expansion (the genetic cause linked to Friedreich’s ataxia) and 93 healthy volunteers.

The study participants were recruited at UCLA and at Children’s Hospital of Philadelphia.

The team identified 829 genes that were differently expressed between patients and controls, 1,078 between patients and carriers, and 182 genes with different activity levels between carriers and controls.

When they analyzed the information taking into account the patients’ disability stage and clinical features, they identified 1,508 genes that were significantly associated with functional disability stage, 280 genes linked to FXN gene expansion, and 13 genes significantly linked to disease duration.

Interestingly, many of the identified genes are known to be involved in inflammatory immune response mediated by neutrophils (immune system cells) and have been shown to be relevant in other neurodegenerative diseases.

Comparison of this genetic information with that reported in nerve cells collected from mouse models of Friedreich’s ataxia failed to demonstrate an overlap. This could in part be due to “the large differences in structure and function between cells of the central nervous system and peripheral blood,” the researchers wrote.

Still, they found that some of the genes identified had already been reported to be altered in the heart of mice with Friedreich’s ataxia. This suggests that similar pro-inflammatory mechanisms may occur in the heart and in peripheral blood.

Supported by these findings, the team believes that “the inflammation occurring in Friedreich’s ataxia is not an acute response to an infection or a traumatic injury.”

Instead, it’s more similar to “the chronic low-grade inflammation observed in other neurodegenerative and inflammatory disorders.”

Additional studies are needed to better understand if this inflammatory process contributes to the disease progression or if it is just a response to the cellular stress induced by the loss of frataxin, the team said.