Choroideremia: from genetic and clinical phenotyping to gene therapy and future treatments. (December 2018)

• Record Type: Journal Article
• Authors: Mitsios, Andreas; Dubis, Adam M.; Moosajee, Mariya
• Is Part Of: Therapeutic advances in ophthalmology. Volume 10(2018)
• Publication Date: 2018-12
• Subjects: choroideremia -- gene therapy -- nonsense suppression therapy -- REP1 -- retinal dystrophy -- stem cells; Ophthalmology -- Periodicals; Eye -- Diseases -- Periodicals; 617.7005
• DOI: 10.1177/2515841418817490
• Languages: English
• ISSNs: 2515-8414

Abstract

Choroideremia is an X-linked inherited chorioretinal dystrophy leading to blindness by late adulthood. Choroideremia is caused by mutations in the CHM gene which encodes Rab escort protein 1 (REP1), an ubiquitously expressed protein involved in intracellular trafficking and prenylation activity. The exact site of pathogenesis remains unclear but results in degeneration of the photoreceptors, retinal pigment epithelium and choroid. Animal and stem cell models have been used to study the molecular defects in choroideremia and test effectiveness of treatment interventions. Natural history studies of choroideremia have provided additional insight into the clinical phenotype of the condition and prepared the way for clinical trials aiming to investigate the safety and efficacy of suitable therapies. In this review, we provide a summary of the current knowledge on the genetics, pathophysiology, clinical features and therapeutic strategies that might become available for choroideremia in the future, including gene therapy, stem cell treatment and small-molecule drugs with nonsense suppression action.