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Paris, november 25 1999

Dear Colleagues and Friends,

I contact you to keep you informed on the recent progresses observed in the treatment of heart hypertrophy in Friedreich Ataxia by idebenone (Mnesis) oral supplementation and on the delicate problem we are now facing. We recently reported a preliminary study showing the positive effect of the drug on the cardiomyopathy on three patients ( Rustin, P., von Kleist-Retzow, J.-C., Chantrel-Groussard, K., Sidi, D., Munnich, A., Rˆtig, A. (1998) Effect of idebenone in Friedreich's ataxia: a preliminary study. The Lancet 354: 477-479; Rustin, P., Munnich, A., Rˆtig, A. (1998) Quinone analogs prevent enzymes targeted in Friedreich ataxia from iron-induced injury in vitro. Biofactor 1999;9(2-4):247-51; 136. Rustin P, von Kleist-Retzow JC, Chantrel-Groussard K, Sidi D, Munnich A, Rˆtig A. Ataxie de Friedreich : 3 ans aprËs l'identification du gËne, un premier espoir d'enrayer le cours de la maladie. MÈdecine/Science (in press); von Kleist-Retzow, J.C., Chantrel-Groussard, K., Sidi, D., Munnich, A., Rôtig, A. und Rustin, P. (1999) Die Friedreich'sche Ataxie: 3 Jahre nach Identifikation des Gens ein Hoffnungsschimmer für die Therapie.

Deutsche Medizinische Wochenschrift (in press);
all available upon request at my email address: rustin@necker.fr ).   We have now new results on 21 patients, aged 6 to 21 years, after 4 to 18 months of treatments. 16 (aged 9-24 y) on 21 patients have a significant reduction of their heart hypertrophy (>30%). This was observed for 50% of these patients after 4 months of treatment (5 mg idebenone/kg/d). 2 (both aged 12 y) on 21 had a slight decrease of less than 30% (treatment: 3 and 8 months). 3 (6, 11, 21 years old) on 21 had no change after 3, 6 or 8 months of treatment.
No patient showed an increase in hypertrophy during this short period. None of the patients complained of undesirable side effects. Several patients noticed general improvement of their condition, in particular less fatigability. Delicate movements also seemed improved for several of the patients. More quantitative information on neurological effect of the drug will be available at the end of the trial presently taking place in France and planned to last two years.

  Therefore, in light of the present data, it is already quite clear that idebenone is a very promising drug. However, first, additional open trials should be rapidly started in other places with perhaps other posology or in association with other drugs that may further improve the defense of the organism against iron. Second, because the cardiomyopathy in this disease may reveal quite dangerous, the drug should be made available for all the patients at risk as soon as possible.

But we are now facing a dramatic problem since the drug is not produced any more by the manufacturer (Takeda Company in Japan), which few years ago distributed it in several countries all around the world. An unknown amount of the drug is still available in several countries, and is currently available through the Internet (about 3 000 $/y for an adult), but this is a limited amount and we are facing the risk to get short of the drug rapidly. Contact with Takeda is now established in France since more than two years, and in the US, through the NIH, since several months. All information we have from our present French trial has been made available to all people possibly concerned (and is still available to all of you). Despite this, there is still no clear indication that Takeda will decide the resumption of the production, although a positive outcome is perhaps still possible (... as it is since one year!).

  We therefore took the decision today to publicize the situation at the beginning of December taking the opportunity given to us by the French Telethon at the TV in order to put maximal pressure on Takeda to obtain the resumption of the production. With a similar aim, I think that parallel pressure should be made coming from as many places as possible, thereof this email which is send simultaneously to both patient's associations, concerned individuals, and several clinicians in charge. Let me now your ideas to reach this goal and please publicize the information included in this mail as much as possible.

Yours sincerely,

Pierre Rustin,
PhD,
Research Director at the C.N.R.S.
(Centre National de la Recherche Scientifique, France)

email: rustin@necker.fr
INSERM U-393; Hopital Necker Enfants Malades
149, rue de Sevres; F-75015 Paris
Tel: (+33) 1 44 38 15 84
Fax: (+33) 1 47 34 85 14