Efficacy of Epoetin Alfa in Patients With Friedreich's Ataxia

Single-Center, Open-Label, Sequential Trial to Test the Efficacy, Safety and Tolerability of Epoetin Alfa in Patients With Friedreich's Ataxia

Friedreich's ataxia is a rare genetic disorder characterized by severe neurological disability and cardiomyopathy. Friedreich's ataxia is the consequence of frataxin deficiency. Although several drugs have been proposed, there is no available treatment. It was recently demonstrated that erythropoietin can increase the intracellular levels of frataxin in an in-vitro model. The present project is aimed at testing the possible therapeutic approach of erythropoietin, which is an already available and commercialized drug. The investigators will perform both in-vitro and in-vivo tests, in order to asses its efficacy and safety in patients. The results will be useful to plan further clinical trials.

Friedreich ataxia (FRDA) is an inherited recessive disorder characterized by progressive neurological disability. FRDA is the consequence of frataxin deficiency. Although several drugs have been proposed for FRDA, there is no available treatment. Recently it was shown that recombinant human erythropoietin (rhu-EPO) administration increases frataxin expression in cultured human lymphocytes of FRDA patients. It is therefore of primary importance to test extensively rhu-EPO's ability in increasing frataxin levels in-vitro and in-vivo. In addition rhu-EPO is an already available and commercialized drug approved for the treatment of anaemia associated with chronic renal disease, heart failure and cancer. Towards this overall purpose, we will perform an acute clinical trial in FRDA patients with rhu-EPO and will assess its effect in-vivo on frataxin expression. In addition, rhu-EPO's safety in FRDA patients based on laboratory parameters and neurological indexes will be tested. The results will be useful to gain new insight in the role of rhu-EPO in FRDA, and in the future, it may be useful to plan further clinical trials.

Patients that will satisfy all inclusion/exclusion criteria will be sequentially treated with three single Epoetin alfa administrations. The first time the dose will be 600U/KG BW s.c. in a single administration. The outcome measures will be assessed. A washout period of 1 month will be necessary to eliminate any carry-over effect. A second administration of 1200U/KG BW s.c. will be performed. Outcome measures will be again assessed.

Primary endpoint will be the frataxin level in PBMCs from patients at different timing from a single Epoetin alfa administration.

Inclusion Criteria: Molecular diagnosis of FA based on a homozygous GAA expansion within the FRDA with a triplet repeat sequence in the pathological range. Age >18, <50 years Exclusion Criteria: Failure to meet one of the inclusion criteria Patients in treatment with Idebenone Wheelchair bound patients Significant renal, hepatic or haematological disease Positive history for arterial or venous thrombosis Acute diseases that might interfere with the study Positive history for arterial hypertension Present or programmed pregnancy Known hypersensitivity to study drug Other unacceptable concomitant medications (in particular agents thought to have a neuroprotective potential as tocopherol, amantadine, memantine, free radical scavengers).