Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disease. FRDA is the most frequent inherited ataxia, which usually presents in childhood and is characterized by impaired coordination, slurred speech, peripheral neuropathy and cardiomyopathy, frequently leading to severe disability by early adulthood. FRDA is caused by a partial deficiency in the mitochondrial protein frataxin (below 25-30% of normal), which is thought to act as molecular chaperone and iron storage protein.
There is currently no specific treatment for FRDA however the recent discovery that histone deacetylase (HDAC) inhibitors can induce frataxin gene up-regulation has revealed the potential for a radical new therapy for this disease (Festenstein, 2006). In a previous study, Vitamin B3 (nicotinamide, a classical class III HDAC inhibitor) was shown to restore frataxin levels to normal in primary lymphocytes from FRDA patients after incubation for 24-72 hours. Likewise, nicotinamide treatment up-regulates FXN in cerebellum (a tissue affected in FRDA) derived from a mouse model for FRDA when injected intraperitoneally after 24hours and this effect is sustained after daily dosing for 5 days.
The aim of the present study is to investigate whether high doses of nicotinamide (up to 8g) are safe and tolerated in FRDA patients and can up-regulate frataxin in FRDA patients, following single (part 1) and repeated daily administration for 5 days (part 2). Based on the outcomes of part 1 and part 2 of the study, patients will be offered the possibility to enter part 3 of the study aiming at assessing a longer-term safety and possible clinical benefit of nicotinamide, following daily dosing for two months. The study has received all regulatory approvals and is ready to start. Approximately 10 patients have expressed an interest in participating in the study. The study is expected to complete by 2Q13.
PI: Prof Richard Festenstein, Dr Vincenzo Libri