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Friedriech’s Ataxia or Mitochondrial Disease

Friedreich’s ataxia is a hereditary genetic disease. A gene (a segment of a chromosome) which is defective is its cause. This gene is found on chromosome 9.

The FA gene, like all other genes, contains the information for the building of a protein (a sequence of amino acids) which is called “frataxine”, a protein composed of 216 amino acids.

To begin with, one must know that chromosomes are small structures situated in the core of cells and which serve as support for genetic characteristics. The chromosomes transmit the hereditary characteristics of living beings to their descendants. Chemically, a chromosome is formed by a molecule : the DNA. The DNA contains all the genetic information of an individual and it is this which allows the transmitting of this information from one generation to another. DNA is formed of 4 bases : adenine (A), guanine (G), cytosine (C) and thymine (T).The genetic information consists of hundreds of bases organized in triplets which encode for different elements composing the protein, the amino acids.

To this day, with the majority of persons afflicted with FA, one was able to notice a significant change on the level of the DNA of the cell, in the gene which contains the information necessary for the building of frataxine. In the DNA of this gene, one observes a significant number of repetitions of the GAA sequence (guanine, adenine, adenine) which form a triplet repeated in many copies.

In a normal person, the GAA triplets are repeated 7 to 22 times compared to the case of an ataxic person where it is 150 to 1,000 times. This high rate of repetition leads to a deficiency in the protein which is built from this erroneous information, frataxine.

We do not yet know completely the role of frataxine in the organism but that which we are certain of is that :

  1. Frataxine is a protein which is indispensable to the proper functioning of the tissues of certain organs. It is present in a very small quantity in a person afflicted with FA.
  2. Frataxine is found in the mitochondria of each cell, a mitochondrion being a structure of the cytoplasm of the cell situated in the interior of the cellular membrane. All our cells contain mitochondria. It is the place for the production of the energy necessary for the functioning of our cells. Mitochondria are small energy centrals. The mitochondria build 90% of the cellular energy of the tissues, the organs which the entire organism needs in order to function. It is thanks to them if we can think, if we can run, if we can stand up, etc. The mitochondria contain enzymes which accelerate the reactions of the transformation of food into energy and which allow the cell to use the oxygen which it needs. One can say that the mitochondria are the lungs of the cell.
  3. Frataxine plays an important role in determining the quantity of iron which enters the mitochondria and their way of using it. Researchers observed that frataxine serves as a regulator for the entrance of iron into the mitochondria. Frataxine existing in a reduced quantity in a person afflicted with FA, the entrance of iron is poorly controlled which gives rise to a too great quantity of iron being found in the mitochondria.

This excess iron interacts with the oxygen present in the interior of the mitochondria to form toxic molecules which are called “free radicals”. These free radicals alter the functioning of the mitochondria and prevent the production of the energy necessary for the proper functioning of the cells.

Certainly our organism is equipped with a natural system for the elimination of free radicals such as enzymes and antioxidants like dismutase superoxide, co-enzyme Q, glutathion and catalase. Eliminating the free radicals created by our mitochondria prevents our neurons from being damaged. The more we age and the more this system weakens, increasing the number of free radicals and by the very fact, the possibility of damage to the neurons.

By performing a biopsy of the heart of a person afflicted with FA, a deficiency in iron-sulphur proteins was discovered in the mitochondria. Now this deficit is found only in the cells of the nervous system and in the heart but other cells like those of the muscles, the lymphocytes and the fibroblasts are normal.

Because of the accumulation of iron in the mitochondria, responsible for the appearance of toxic free radicals which attack the iron-sulphur proteins, doctors had the idea of prescribing an antioxidant (a substance preventing oxidations). Several antioxidants have been studied but only one has been kept because :

  1. it easily passes through the membranes of the cells and the mitochondria;
  2. it captures the free radicals and the superoxide ions;
  3. it evacuates them towards the respiratory chain by complex 3 before they have been able to attack the iron-sulphur proteins and it is without side-effects in the patients.

Our organism is already provided with natural antioxidants such as coenzyme Q-10 but knowing that one of the same nature exists, a quinine, and which proves much more powerful, it has been decided that IDEBENONE would be the best candidate to treat these patients.

The TAKEDA firm is Japan which has a subsidiary in France, is the only firm in the world which makes it. Idebenone has been tested in France in three young patients and the results have been very encouraging. “In a short time, cardiac hypertrophy (a thickening of the walls of the heart) which can be lethal in this disease, diminished significantly and the product is perfectly tolerated. The short duration of this trial did not allow us to notice changes on the level of neurological afflictions, but all the ill noticed an improvement in muscular strength and the precision of movements”, state the authors of the study.

Two French teams decided to set up a clinical trial experiment with 52 patients, of whom 20 were children. In Quebec, we are following close behind with both children and adults. The experiment started in September 1999.

It is still too early to give the results but having met some of the youths, on a neurological level they noticed better balance, better manual dexterity as well as better speech. Is it subjective ? We will know later on following tests.

IDEBENONE is perhaps not a “miracle cure”, but in any case it can slow down the evolution of the disease.

In 2005, researchers are also looking at new substances having interesting properties which will come to be added to idebenone in order to improve it.


By Nicole St-Jean
Revised by Dr. Madeleine Roy, Montreal Clinical Research Institute


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