Background: Friedreich's Ataxia (FRDA) is an inherited and slowly progressive neurodegenerative disease. Clinically, the neuromuscular disorder is characterized by multiple symptoms including muscle weakness, speech problems, progressive gait and limb ataxia, dysarthria, diabetes mellitus and hypertrophic cardiomyopathy. A defect in the gene encoding the protein Frataxin resulting in decreased levels of this protein has been reported to be responsible for the development of FRDA. FRDA is the most prevalent inherited ataxia, affecting about 1 in every 50,000 people. Currently no effective cure or treatment is available for FRDA.
Technology: Researchers from an Austrian university developed a new treatment strategy focusing on the molecular cause of FRDA. They found that Erythropoietin (EPO) is able to increase Frataxin levels in vitro and in vivo. These results indicate that EPO is a promising candidate for the development of the first causal treatment of FRDA.
EPO is a well known human recombinant protein which has been in clinical use for several years and has a well documented safety profile.
Development Status:
In vitro & in vivo Results: The Frataxin-increasing effect of EPO has been shown in human cell lines, in isolated primary cells from FRDA patients and in non-FRDA patients.
Clinical Proof-of-Concept Study: A 2 months open label study with 12 FRDA patients demonstrated the efficiency of EPO for the treatment of FRDA. A significant increase in Frataxin levels after 2 months could be achieved.
Clinical Phase-II Study: A 6 months open label study with 8 FRDA patients clearly showed evidence for clinical improvement together with a persistent increase of Frataxin levels. Additionally, oxidative stress markers (urine 8-OHdG, peroxides) which are known to be increased in FRDA patients were highly significantly reduced.
Dose-finding Study: 5 patients received 3 times rhuEPO (5000, 10000 and 30000 U) with a wash-out phase of 1 month between each injection. A very significant increase in Frataxin levels over time could be observed. These data are in
accordance with a trial performed in Italy.
Clinical Study in progress (Phase II): 8 patients will receive rhuEPO for 2 months and muscle biopsies will be collected. Frataxin levels and parameters for energy production in the muscle will be analysed.
Innovative Aspects:
- First causal treatment option for Friedreich´s Ataxia.
- EPO can significantly increase Frataxin, a protein lacking in FRDA patients. This finding gives hope that FRDA could be causally treated by administering EPO to patients. So far there is NO OTHER technology which can raise Frataxin in a comparable manner and which is at an advanced development stage.
- Use of a well known substance (EPO)
- Promising clinical phase II data
- Orphan drug designation
