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. We 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.
Primary Outcome Measures:
- Primary endpoint will be the frataxin level in PBMCs from patients at different timing from a single rhu-EPO administration. [ Time Frame: 0, 24, 48, 96 hours; 7, 15, 30, 60 days ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Echocardiography: Strain and strain rate after rhu-EPO administration at the highest study dose [ Time Frame: 0, 30 days ] [ Designated as safety issue: Yes ]
- safety laboratory parameters, adverse events and tolerability [ Time Frame: 0, 7, 15, 30, 60 days ] [ Designated as safety issue: Yes ]
- International cooperative ataxia rating scale (ICARS), 9-hole peg test (9-hpt) and the 25-feet timed walk will be used. They will explore rhu-EPO safety on gait, stance, limb ataxia, dysarthria, oculomotor disorders, and hand function. [ Time Frame: 0, 7, 30 days ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: |
10 |
| Study Start Date: |
February 2008 |
| Estimated Study Completion Date: |
February 2009 |
| Estimated Primary Completion Date: |
December 2008 (Final data collection date for primary outcome measure) |
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I: Experimental
Treatment arm
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Drug: Epoetin alfa
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, a washout of 2 months will be necessary. The third administration will be 2400U/Kg BW s.c. Outcome measures will again be assessed.
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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.
Purpose
