Jan. 30, 2001

FRIEDREICH'S ATAXIA UPDATE NEW MOUSE MODEL OF FRIEDREICH'S ATAXIA CREATED

For the first time, MDA-funded researchers have created mutant mice that will be useful for testing potential treatments for the inherited neurological disease Friedreich's ataxia (FRDA or FA).

FA attacks parts of the nervous system that control movement and reflexes, leading to a loss of coordination and some types of sensation. About 90 percent of the time, FA also has potentially life-threatening effects on cardiac muscle.

In 1996, MDA-funded researchers discovered that FA is caused by mutations in a previously unknown gene for a protein which they named frataxin. Later, in an attempt to shed light on frataxin's function and provide a useful disease model, another MDA-funded research team created a line of frataxin-deficient mice. Unfortunately, those mice couldn't be studied because they died during embryonic life.

Now, the same research team has used sophisticated genetic techniques to create mice that have a frataxin deficiency restricted to either their muscle (including cardiac) tissue, or their cardiac and nervous tissues. The team, led by Michel Koenig of the Institute of Genetics and Molecular and Cellular Biology in Strasbourg, France, presents its results in the February issue of Nature Genetics.

Both types of frataxin-deficient mice, the team found, survive into adulthood and develop heart defects similar to those experienced by people with FA. Also, the mice that lack frataxin in their nervous systems show many of the neurological signs of FA.

Other defects in the mice support a longstanding idea that frataxin affects the storage of iron in mitochondria -- tiny energy factories inside our cells that need iron for certain chemical reactions. Mitochondria from the mice contain abnormal iron deposits, and appear incapable of normal energy production -- a situation that might leave them vulnerable to oxidative stress (a type of damage from free radicals).

The new mouse model, the researchers say, will be useful for further deciphering frataxin's functions and for evaluating possible treatments for FA, including antioxidants and iron-binding drugs.