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Persistence of the treatment effect of idebenone in Leber’s hereditary optic neuropathy

T. Klopstock, G. Metz, P. Yu-Wai-Man, B. Büchner, C. Gallenmüller, M. Bailie, N. Nwali, P. G. Griffiths, B. von Livonius, L. Reznicek, J. Rouleau, N. Coppard, T. Meier, P. F. Chinnery
DOI: http://dx.doi.org/10.1093/brain/aws279 e230 First published online: 6 February 2013


Sir, There is a growing body of evidence supporting the beneficial effects of idebenone in Leber’s hereditary optic neuropathy (LHON, MIM 353500), an inherited mitochondrial disease that causes rapid bilateral vision loss and lifelong legal blindness. Until recently, reports were limited to isolated case studies and small open-label case series (Mashima et al., 1992, 2000; Cortelli et al., 1997; Carelli et al., 1998, 2001; Barnils et al., 2007). However, in 2011, two articles published in Brain provided additional evidence for the therapeutic use of idebenone in LHON (Carelli et al., 2011; Klopstock et al., 2011).

In the first complete randomized, placebo-controlled, double-blind clinical trial in LHON [Rescue of Hereditary Optic Disease Outpatient Study (RHODOS), ClinicalTrials.gov identifier: NCT00747487], 85 unselected patients with LHON ≥14 years of age were randomized to receive 900 mg/day of idebenone or placebo in a 2:1 ratio for 24 weeks (Klopstock et al., 2011). In the intent-to-treat population, visual acuity data were available for 82 patients harbouring one of the three primary mitochondrial DNA mutations (m.11778G>A, m.3460G>A and m.14484T>C) and experiencing first vision loss up to 5 years before study enrolment. All visual acuity end-points in the intent-to-treat population showed a consistent trend, with idebenone protecting patients from further vision loss, in contrast to the placebo group where visual acuity continued to deteriorate. Efficacy seen on visual acuity end-points was supported by independent measures including tests of colour contrast sensitivity. Following a pre-specified analysis by mutation, exclusion of patients with the m.14484T>C mutation, which is known for its high spontaneous recovery rate, resulted in a larger treatment effect in all visual acuity end-points. This finding was in agreement with the data from a retrospective analysis of 103 patients, published in the …

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