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Review
. 2023 Sep 20;24(18):14354.
doi: 10.3390/ijms241814354.

Choroideremia: The Endpoint Endgame

Maram E A Abdalla Elsayed  1   2 , Laura J Taylor  1   2 , Amandeep S Josan  1   2 , M Dominik Fischer  1   2 , Robert E MacLaren  1   2
Affiliations
Review

Choroideremia: The Endpoint Endgame

Maram E A Abdalla Elsayed et al. Int J Mol Sci. .

Abstract

Choroideremia is an X-linked retinal degeneration resulting from the progressive, centripetal loss of photoreceptors and choriocapillaris, secondary to the degeneration of the retinal pigment epithelium. Affected individuals present in late childhood or early teenage years with nyctalopia and progressive peripheral visual loss. Typically, by the fourth decade, the macula and fovea also degenerate, resulting in advanced sight loss. Currently, there are no approved treatments for this condition. Gene therapy offers the most promising therapeutic modality for halting or regressing functional loss. The aims of the current review are to highlight the lessons learnt from clinical trials in choroideremia, review endpoints, and propose a future strategy for clinical trials.

Keywords: AAV; CHM gene; REP1; antisense oligonucleotides; choroideremia; clinical trials; endpoints; gene therapy; nonsense suppression therapy; outcome measures.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pseudo-colour fundus image (Optos, Dumfernline, UK) demonstrating the choroideremia phenotype in an affected, non-treated male with no foveal involvement. The arrow points towards the residual island of preserved central macula.
Figure 2
Figure 2
Pseudo-colour fundus image (Optos, Dumfernline, UK) demonstrating retinal degeneration advancement towards the fovea. There is extensive choroidal atrophy and the underlying sclera is visible.
Figure 3
Figure 3
Spectral domain optical coherence tomography, Heidelberg, Germany shows outer retinal atrophy involving the fovea—the nasal macula is more severely affected than the temporal macula.
See this image and copyright information in PMC

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