Preliminary results of therapeutics trials in Friedreich's ataxia


At the Royal Free Hospital in England, research into FA continues to target three major avenues of research:
* identifying the underlying biochemical and morphological effects of the genetic mutation using tissue samples and cells in culture donated by patients either at post mortem or biopsy examination
* studying a group of patients using magnetic resonance spectroscopy and echocardiography to analyse how the genetic defect affects the energy availability to the skeletal muscle and heart
* assessing how a combined vitamin E and coenzyme Q10 therapy affects the energy availability clinical symptoms and heart function in a group of 10 patients.

The study of tissue and cells has shown that, particularly in heart tissue from FA patients, there is an accumulation of iron, which seems to be in the energy producing component of the cell "the mitochondrion". The mitochondrion may be tough of as "the batterie" of the cell. In addition we have been able to show:

- a decrease in the energy generating machinery of the mitochondria-
- an increased susceptibility of cells from FRDA patients to attack by free radicals.

Together this implies that the underlying cause of FRDA may involve:
* abnormal mitochondrial iron regulation
* abnormal mitochondrial energy supply to the cells
* increased sensitivity to free radical damage.

Using MRS analysis, we have been able to detect a decrease in the energy availabillity to the heart and skeletal muscle in 17 FA patients. This is particularly important. It not only implies that patients'tissue is contributing to their clinical symptoms but has also given us a marker by which we can assess the efficacity of putative therapies.

Lastly, and perhaps most exciting of all, we aree currently assessing a combined coenzyme Q10 and vitamin E therapy.

To strengten the ability of the mitochondria to supply energy in patients' cells we are using a substance which is naturally involve in the mitochondrial energy generating machinery, called coenzyme Q10. In addition both coenzyme Q-10 and vitamin E are anti-oxydants helpind to protect the cell from domaging free radicals which appear to be increased in FA patients.
We currently have 10 patients on therapy and have assessed them before therapy began and then after 3, 6 et 12 months of therapy. We have used a variety of parameters: clinical assessment of symptoms. MRS analysis of heart and skeletal muscle energy availability; and echocardiogram analysis of the heart. The initial trial is for a period of 12 months which we hope to be able to extend for a further 12 months.

The pre-therapy and 3 month therapy assessments therapy have been undertaken and the 6 month therapy data are currently being analysed. The data are still to preliminary to make any clear conclusion, but we are generally encouraged by the improvements in the MRS data we have seen after 3 months of therapy, although the clinical assessments of the patients show, no significant change.
This is not unexpected as most clinical symptoms of FA are due to loss of neurones which will no recover. Consequently, we are looking for a slowing down of the clinical progression of the disease. We would like to take this opportunity to advise FA patients to be cautious regarding the uncontrolled use of putative therapies and strongly recommand they should only be taken in consultation with their neurologist .


Was choosen from The Ataxian magazine