Nov. 13, 2008

Potential Therapeutic Path Shown in FA

Experiments examining the effects of iron chelation, a process that removes toxic levels of iron from cells, have provided insight to the potential therapeutic value of the process in Friedreich's ataxia (FA).

A deficiency of the frataxin protein, the underlying cause of FA, changes the way the body regulates iron levels and leads to toxic levels of iron in the cellular energy factories known as mitochondria. The disease damages the heart and nervous system.

Iron chelation limits the harmful increase in cell size in the muscle tissue of the heart (myocardial hypertrophy) in mice with a disease that closely mimics FA, say researchers at the University of Sydney in Australia.

The investigators, who also added to the understanding of FA at the molecular level, published their findings in the July 15 issue of Proceedings of the National Academy of Sciences. MDA supported Des Richardson at the University of Sydney for this work.

The FA mice received iron chelation therapy with a compound that penetrates mitochondria starting at age 4.5 weeks, before effects of the disease are present, and then five days a week until they reached 8.5 weeks and had pronounced symptoms. The chelation-treated mice showed a marked and significant decrease in cardiac iron levels compared to those treated with a placebo.

The investigators note that, although chelation reduced iron levels and limited cardiac hypertrophy in the FA mice, the animals still had decreased cardiac function as well as the weight loss and hunched stance typical of those with the FA-like defect.

Importantly, however, the chelation didn’t lead to overall body iron depletion in the mouse, or toxicity, making it a potential therapeutic strategy for the disease.

The study results are “very important in understanding and treatment of the highly aggressive neurodegenerative and cardiodegenerative disease Friedreich’s ataxia,” said Richardson.

“We’ve demonstrated for the first time the processes responsible for the iron loading that underlies Friedreich's ataxia and uncovered a possible treatment strategy to target the toxic iron accumulation and remove it.”