Friedreich's Ataxia (FA) is a genetic, hereditary disease. A defective gene (a chromosome segment) causes it. This gene is located on chromosome 9.

Like every other gene, the gene for FA contains information to make a protein (a sequence of amino acids) called "frataxin", a 216 amino acid protein.

It is important to know that chromosomes are small structures located in the cell nucleus, and they act as a support of genetic information. The chromosomes transmit the genetic information of living creatures to their progeny. Chemically, the chromosome is formed of a DNA molecule. The DNA contains all the genetic information of an individual and it enables the information to be transmitted from one generation to the next. The DNA is formed of four bases: adenine (A), guanine (G), cytosine (C) and thymidine (T). The genetic information is made of hundred of bases, organized in triplets, that code for the element of a protein: the amino acids.

In most FA patients, we notice an important modification of cellular DNA, in the gene for frataxin. In the DNA for that gene, there is an important number of repetitions of the sequence GAA (guanine, adenine, adenine).

This is called a triplet repeat and it is normally found 7 to 22 times in a normal person. In a FA patient, the repeat is found 150 to 1000 times. This high repetition rate causes a decrease in frataxin levels.

The role of frataxin is not yet known, but we are sure that:

1)Frataxin is an essential protein for the function of tissues in certain organs. It is present in very small quantities in FA patients.
2)Frataxin is found in mitochondrias. The mitochondria is a cellular organelle found in cell cytoplasm, which is the inside of the cell.

All the cells contain mitochondria. It is the site for energy production; the mitochondrias are small power plant. The mitochondria makes 90% of the energy needed by the tissues, the organs and the entire organism to function. Thanks to them, we can think, run, stand, etc. The mitochondria contain enzymes that transform food into energy and then allow the cell to use the oxygen that it needs. We can say that the mitochondria is the lung of the cell.

3)Frataxin plays an important role in determining how much iron enters the mitochondria and how it will be used. Researchers realized that frataxin acted as a regulator for the entrance of iron in the mitochondria. Since levels of frataxin are decreased in FA patients, the entrance of iron is nor well controlled and too much iron ends up in the mitochondria.

This iron reacts with the oxygen present in the mitochondria and forms toxic molecules called free radicals. Those free radicals alter the function of the mitochondria and keep it from producing the necessary energy for the cell.

Of course, the body has a natural way of eliminating the free radicals, such as enzymes and natural antioxidants like superoxyde dismutase, co-enzyme Q, glutathion and catalase. If FA patients could eliminate those free radicals, it would keep them from destroying neurons. As we get older, this system weakens, raising the level of free radicals and the possibilities of neuronal damage.

By doing a heart biopsy of a FA patient, we discovered a deficit in iron-sulphur proteins in the mitochondria. This deficit is found only in nerve and heart cells, muscle cells, lymphocytes and fibroblasts are normal.

Because of the accumulation of free radicals in the cells of FA patients that attack iron-sulphur proteins, doctors had the idea of giving anti-oxidants to the patients. Many anti-oxidants have been studied but one was chosen because:
1)It can easily cross cell and mitochondria membranes
2)picks up free radicals and super oxide ions
3)It evacuates them towards the respiratory chain via complex 3 before they can attack iron-sulphur proteins
4)It has no adverse effects in the patients

Our body already has natural anti-oxidants, such as co-enzyme Q, but knowing that there is an analog, a quinone, that is much more powerful, it was decided that IDEBENONE would be the best candidate to treat FA patients.

The Japanese firm TAKEDA is the only company that makes Idebenone. It has already bees tested in France in three young patients and the results are very encouraging. The authors of the study report that cardiac hypertrophy (thickening of heart walls), that can be fatal in this disease, significantly decreased and the medication is well tolerated. The short duration of the trial did not allows to see any changes in the neurological functions, but close relatives of the patients noticed an increase in muscles strength and movement precision.

Two French teams decided to start a clinical trial with 52 patients including 20 children. In Quebec, clinical trials were started in September 1999 with children and adults.

It is still to early to interpret results, but young patients claim to have a better balance, improved manual dexterity and improved speech. Is this subjective, we will know later with tests.

Idebenone might not be the miracle cure, but it might be able to slow the evolution of the disease.

Idebenone has been developed to treat elderly people suffering from memory losses. Unfortunately, studies were not concluding and Takeda decided to stop making it. Following pressure from a French physician working on FA, the company decided to wait for the results of the ongoing clinical trials before deciding the future of Idebenone.

Just like Takeda, we are anxiously waiting to the results from the clinical trials, but it is possible that the combination of Idebenone with other substances can improve its efficiency.

A story to follow...

By Nicole St-Jean
reread and verified by Dr. Madeleine Roy ,IRCM
translated by Fanny Chagnon