Study of the Efficacy and Safety of Nicotinamide in Patients With Friedreich Ataxia
Status:
Not yet recruiting
Trial end date:
2023-12-01
Target enrollment:
Participant gender:
Summary
Friedreich ataxia is the most frequent early-onset autosomal recessive hereditary ataxia. It
is caused by a pathological expansion of a GAA repeat in the first intron of the frataxin
gene (FXN) and results in decreased levels of FXN protein. FXN deficiency results in a
relentlessly progressive neurodegenerative condition which frequently presents around
puberty. Patients gradually lose coordination, become dysarthric and are frequently
wheel-chair bound as adolescents. There is no disease modifying therapy and many patients die
prematurely of cardiomyopathy. It was subsequently found that the FXN gene is silenced at the
chromatin level by the formation of heterochromatin and that this heterochromatin formation
can be antagonized by histone deacetylase inhibitors (HDACi) (Chan et al., 2013). A recent
proof-of-concept clinical study on ten patients with Friedreich ataxia demonstrated that FXN
levels can be restored to those seen in asymptomatic carriers using the class III HDACi
nicotinamide at a dose that is well tolerated by patients (Libri et al., 2014). Since
carriers are asymptomatic, this degree of restoration of FXN expression might be expected to
halt disease progression. Nicotinamide readily crosses the blood brain barrier and has
previously been given at high doses for long periods to normal individuals without serious
adverse effects (Gale et al., 2004; Knip et al., 2000). This study will be the first to
provide clinical evidence for the efficacy and safety of nicotinamide in patients with
Friedreich´s ataxia.