Friedreich ataxia (FRDA) is an autosomal recessive inherited
neurodegenerative disorder leading to reduced expression of the
mitochondrial protein frataxin. Previous studies showed
frataxin upregulation in FRDA following treatment with recombinant human
erythropoietin (rhuEPO). Dose-response interactions between
frataxin and rhuEPO have not been studied until to date. We administered escalating rhuEPO single doses (5,000, 10,000 and 30,000 IU) in monthly intervals to five adult FRDA patients. Measurements of
frataxin, serum
erythropoietin levels,
iron metabolism and mitochondrial function were carried out. Clinical outcome was assessed using the "Scale for the assessment and rating of
ataxia". We found maximal
erythropoietin serum concentrations 24 h after rhuEPO application which is comparable to healthy subjects.
Frataxin levels increased significantly over 3 months, while
ataxia rating did not reveal clinical improvement. All FRDA patients had considerable
ferritin decrease.
NADH/
NAD ratio, an
indicator of mitochondrial function, increased following rhuEPO treatment. In addition to
frataxin upregulation in response to continuous low-dose rhuEPO application shown in previous studies, our results indicate for a long-lasting
frataxin increase after single high-dose rhuEPO administration. To detect
frataxin-derived
neuroprotective effects resulting in clinically relevant improvement, well-designed studies with extended time frame are required.