Oral treatment for Leber congenital amaurosis

Posted by & filed under Part 29: EYE.

Koenekoop RK et al. Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial. Lancet. 2014 Jul 11. [Epub ahead of print]

Perusek L, Maeda T. Vitamin A derivatives as treatment options for retinal degenerative diseases. Nutrients. 2013 Jul 12;5(7):2646-66.


Koenekoop et al describe a successful open-label, prospective, phase 1b trial for oral synthetic 9-cis-retinyl acetate in the treatment of RPE65 or LRAT-related Leber congenital amaurosis. Mutations in RPE65 or LRAT block the retinoid cycle and cause a deficiency of the visual chromophore 11-cis-retinal; chronic deficiency of 11-cis-retinal leads to photoreceptor degeneration, but this does not seem to occur immediately, thus providing a window of opportunity for treatment (for a clear and interesting review of the visual cycle and the potential of vitamin A derivatives as treatment options, cf. the 2013 review by Perusek and Maeda). In this study, 11-cis-retinal was replaced by 9-cis-retinal in 14 patients with RPE65 or LRAT-related Leber congenital amaurosis; patients were treated orally for seven days. A majority of patients had clinically significant improvement in visual function, with no serious side effects; surprisingly, in six patients, the treatment effect persisted past 12 months post treatment.

This trial suggests that oral 9-cis-retinal may be a promising non-invasive treatment for the forms of Leber congenital amaurosis that are caused by a block in the retinoid cycle secondary to mutations in RPE65 or LRAT (mutations in these two genes account for about 10% of patients). Further studies are, of course, necessary. It would also be interesting to study the effect of treatment in younger patients (the youngest subject in the study was 6 years old); if 9-cis-retinal therapy is truly effective, perhaps more visual function could be salvaged earlier in the course of the disease.

Posted by Alina Levtova, MD

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