Oral 9-cis retinoid treatment of early-onset retinal dystrophy

Patients Treated With Retinoid

In the online ahead of print issue of the prestigious journal the Lancet researchers of Montreal (Robert Koenekoop), Nijmegen (Frans Cremers and Anneke den Hollander), Rotterdam (Ingeborgh van den Born), and other groups in Brasil, China, and the USA report on the results of a phase 1b trial in 14 persons with early-onset retinal dystrophy due to mutations in LRAT or RPE65.

The photosensitive molecule in rod photoreceptors is rhodopsin, which consists of an opsin protein and a retinoid, 11-cis retinal. Upon photo-excitation, 11-cis retinal is converted to the inactive all-trans retinal and separates from opsin. LRAT and RPE65 are critical enzymes that 'recycle' the inactive all-trans-retinal to active 11-cis retinal. Persons with LRAT or RPE65 mutations show a recessive inherited early-onset retinal dystrophy due to an 11-cis retinal deficiency. In this Lancet study, a synthetic 9-cis retinoid, which can substitute for 11-cis retinal, was orally administered for 7 consecutive days to 14 individuals (ages 7 to 38 years) with LRAT or RPE65 mutations and severely impaired vision. Apart from transient headaches and photophobia, no serious adverse effects were noted. More importantly, 10 of the 14 patients showed significantly improved visual function within one week, which lasted up to 12 months. MRI scans revealed visual responses in the visual cortex correlating with the visual improvement. This drug-based therapy forms an alternative to gene augmentation therapy which previously has been performed through subretinal injection of adeno-associated viruses containing the RPE65 gene.

Cremers, Frans  Hollander, Anneke den (2)

Frans Cremers         Anneke den Hollander



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