Major advance in understanding Friedreich's ataxia

University of Sydney researchers have made a significant advance in understanding the debilitating hereditary disease Friedreich's ataxia, offering hope that new forms of treatment will be developed.

Friedreich's ataxia is a progressive neuro- and cardio-degenerative disease that affects about one in 30 000 people. Neurodegeneration is followed by cardiodegeneration, leading to an early death. In Western populations, around one person in 90 carries the mutant gene that causes the disease and there are about 100 Friedreich's ataxia sufferers in the greater Sydney metropolitan area.

The researchers have discovered how in Friedreich's ataxia sufferers the powerhouse of the cell, the mitochondrion, becomes loaded with toxic iron. This is a significant find that could herald a leap in the understanding and the development of a cure for this condition.

"The terrible part is that these children grow up knowing the joys of self-sufficiency, being able to walk and function normally before they are struck down," said Professor Des Richardson, senior author of the paper. "Now that we can understand how the disease works, we can work on ways to remove the excess iron in this debilitating disease."

The mitochondrion, which is found in all cells, acts as the centre for cell respiration and energy production. Using a mouse model of Friedreich's ataxia the researchers found that the iron loading was caused by increased iron uptake by the mitochondrion and decreased iron release due to reduced iron utilisation in two major mitochondrial pathways. The accumulation of iron in the mitochondrion is toxic and leads to substantial damage to the cell, leading to its death.

Michael Huang, the third-year doctoral student and the first-named author of the paper, noted: "It's great to work on such an intractable disease and by unveiling its underlying nuts and bolts to get results that can potentially help lots of people."

The research has been published in the latest edition of The Proceedings of the National Academy of Science USA, one of the foremost science journals in the world and ranked as an A+ journal by the Australian Research Council.