Choroideremia

An X chromosome-linked abnormality characterized by atrophy of the choroid and degeneration of the retinal pigment epithelium causing night blindness.

Also Known As:

Progressive Tapetochoroidal Dystrophy; Tapetochoroidal Dystrophy, Progressive; Choroideremias; Dystrophies, Progressive Tapetochoroidal; Dystrophy, Progressive Tapetochoroidal; Progressive Tapetochoroidal Dystrophies; Tapetochoroidal Dystrophies, Progressive

Networked: 242 relevant articles (8 outcomes, 31 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Blindness (Hysterical Blindness)
2.	Macular Edema
3.	Disease Progression
4.	Retinal Diseases
5.	Retinitis Pigmentosa (Pigmentary Retinopathy)

Experts

1.	MacLaren, Robert E: 29 articles (07/2022 - 08/2013)
2.	MacDonald, Ian M: 17 articles (01/2021 - 03/2002)
3.	Jolly, Jasleen K: 12 articles (01/2021 - 06/2015)
4.	Xue, Kanmin: 12 articles (01/2021 - 01/2016)
5.	Bennett, Jean: 10 articles (10/2022 - 03/2002)
6.	Seabra, Miguel C: 10 articles (01/2020 - 01/2002)
7.	Aleman, Tomas S: 9 articles (10/2022 - 03/2002)
8.	Maguire, Albert M: 8 articles (10/2022 - 04/2003)
9.	Moosajee, Mariya: 8 articles (01/2022 - 01/2016)
10.	Barnard, Alun R: 8 articles (01/2020 - 07/2013)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Choroideremia:

1.	Retinaldehyde (Retinal)IBA 01/01/2023 - "In patients with choroideremia, mean retinal sensitivities at baseline were significantly greater in the smooth zone (26.1 ± 2.0 dB) versus the mottled zone (20.5 ± 4.2 dB) (P < 0.0001). " 11/01/2019 - "To assess the safety and efficacy of retinal gene therapy with an adeno-associated virus vector (AAV2) designed to deliver a functional version of the CHM gene (AAV2-REP1) for treatment of patients with choroideremia. " 10/01/2023 - "Potential opportunities to enhance future gene therapy studies for choroideremia include optimization of entry criteria (more preserved retinal area), surgical techniques and clinical endpoints. " 01/01/2023 - "Patterns on AF imaging may represent a novel, objective outcome measure for clinical trials in choroideremia as a surrogate for retinal function." 12/01/2021 - "Study of retinal structural-functional relationship in choroideremia using fundus autofluorescence and optical coherence tomography."
2.	dorzolamide (Trusopt)FDA LinkGeneric 04/01/2012 - ": The 2 choroideremia patients treated with dorzolamide 2% formulation had a noticeable reduction in macular thickness by spectral-domain optical coherence tomography. " 04/01/2012 - ": The present study shows the potential efficacy of topical dorzolamide for treating choroideremia patients with cystoid macular edema." 04/01/2012 - "Topical dorzolamide for treatment of cystoid macular edema in patients with choroideremia."
3.	Antisense OligonucleotidesIBA 01/01/2018 - "Antisense Oligonucleotide-Based Splice Correction of a Deep-Intronic Mutation in CHM Underlying Choroideremia." 01/01/2023 - "To assess the long-term safety and efficacy of AAV2-REP1 in choroideremia (CHM) patients, and to test a potential antisense oligonucleotide therapy for CHM. " 01/01/2023 - "AAV2-Mediated Gene Therapy for Choroideremia: 5-Year Results and Alternate Anti-sense Oligonucleotide Therapy."
4.	cytotropic heterogeneous molecular lipid (CHML)IBA 01/01/2019 - "In this study, we report that expression of choroideremia-like (CHML) is increased in HCC, associated with poor survival, early recurrence and more satellite nodules in HCC patients. " 01/15/1994 - "The human choroideremia-like (CHML) gene and a locus for Usher syndrome type 2 (USH2) were recently mapped to the 1q31-qter region employing physical mapping and genetic linkage studies, respectively. " 01/15/1994 - "Mapping of the choroideremia-like (CHML) gene at 1q42-qter and mutation analysis in patients with Usher syndrome type II." 11/01/2021 - "Choroideremia-like (CHML) has been demonstrated to be related to the development of urothelial carcinoma, multiple myeloma, and hepatocellular carcinoma. " 01/01/2018 - "Interestingly, the ZIKV infection signature revealed the downregulation of ALDH5A1 and CHML, genes implicated in neurological (cognitive impairment, expressive language deficit, and mild ataxia) and ophthalmic (choroideremia) disorders, respectively. "
5.	Proteins (Proteins, Gene)FDA Link 10/16/2023 - "The vectors were assessed in two choroideremia disease model systems: (1) CHM patient-derived fibroblasts and (2) chmru848 zebrafish, using Western blotting to detect REP1 protein expression and in vitro prenylation assays to assess the rescue of prenylation function. " 10/01/2021 - "Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). " 01/01/2018 - "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. " 05/01/2014 - "CHM, the gene implicated in choroideremia, encodes Rab escort protein-1 (REP-1), which is involved in the post-translational activation via prenylation of Rab proteins. " 01/01/2014 - "We sought to develop pertinent human cellular IRD models, beginning with choroideremia, caused by mutations in the CHM gene encoding Rab escort protein 1 (REP1). "
6.	DNA (Deoxyribonucleic Acid)IBA 02/26/2015 - "Genomic DNA amplification and whole-genome cytogenic array analysis were used to confirm the diagnosis of choroideremia and determine the molecular basis of the phenotype. " 07/01/2008 - "Genomic DNA was extracted from leukocytes of peripheral blood collected from the affected man and his daughter, who is an obligate carrier of choroideremia. " 12/01/1995 - "A Swedish family with choroideremia and a deletion of the CHM gene has been studied with ophthalmological examination, full-field electroretinography, and DNA analysis in order to characterize the phenotype of the disease. " 06/01/1992 - "Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA sequencing." 11/01/1990 - "In order to characterize a previously described submicroscopic deletion encompassing (part of) the choroideremia (tapetochoroidal dystrophy: TCD) gene, we have cloned a 10.5-kb EcoRI fragment from the patient's DNA; this fragment carries the junction between both deletion endpoints ("junction fragment"). "
7.	Rab geranylgeranyltransferaseIBA 12/01/2011 - "Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase." 01/15/1993 - "Lymphoblasts from choroideremia subjects showed a marked deficiency in the activity of component A, but not component B, of Rab GG transferase. " 09/18/1992 - "Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product." 01/15/1993 - "Retinal degeneration in choroideremia: deficiency of rab geranylgeranyl transferase." 10/13/1995 - "Using recombinant Rab geranylgeranyl transferase and REPs to label unprenylated cytosolic proteins, we identified one unprenylated protein in choroideremia lymphoblasts that was prenylated in vitro more efficiently by REP-1 than by REP-2. "
8.	Retinal Pigments (Pigments, Visual)IBA 01/01/2021 - "Rates of retinal pigment epithelial area loss in 41 patients with choroideremia were measured using fundus autofluorescence imaging for up to 4 years. " 05/01/2020 - "A distinct retinal pigment epithelial cell autofluorescence pattern in choroideremia predicts early involvement of overlying photoreceptors." 07/01/2009 - "Progression of retinal pigment epithelial alterations during long-term follow-up in female carriers of choroideremia and report of a novel CHM mutation." 02/24/2004 - "Mutations in the human gene induce choroideremia, a disease marked by slow-onset degeneration of rod photoreceptors and retinal pigment epithelial cells. " 07/01/2015 - "Choroideremia is a rare X-linked recessive, hereditary retinal pigment epithelial dystrophy, characterized by night blindness and progressive constriction of the visual fields leading to blindness in young adulthood. "
9.	Nonsense Codon (Nonsense Mutation)IBA 01/01/2019 - "Choroideremia (CHM) is an x-linked recessive chorioretinal dystrophy, with 30% caused by nonsense mutations in the CHM gene resulting in an in-frame premature termination codon (PTC). " 03/01/2017 - "A nonsense mutation (c.C799T:p.R267X) of the CHM gene on the X chromosome of the proband (IV:7) and another 5 males with choroideremia were detected, while 3 female carriers with no symptoms were also identified. " 07/01/2004 - "Sequence analysis of the 15 exons of the choroideremia gene and adjacent splice sites is a primary method of mutation detection used by the authors' laboratory, through which a variety of mutations including nonsense mutations, insertions, deletions and splice site alterations have been detected. " 07/01/1994 - "Interestingly, all CHM gene mutations detected thus far in choroideremia patients give rise to the introduction of a premature stop codon." 01/01/2018 - "AAV: adeno-associated virus; BCD: Bietti's crystalline dystrophy; CHM: choroideremia; CHML: choroideremia-like; Dfp: days post-fertilization; EMA: European Medicines Agency; ERG: electroretinogram; ETDRS: Early Treatment Diabetic Retinopathy Study; FDA: Food and Drug Administration; FTase: farnesyl transferase; GFP: green fluorescent protein; GGPP: geranylgeranyl-diphosphate; GGTase-I: geranylgeranyl transferase type-I; GGTase-II: geranylgeranyl transferase type-II; HMG-CoA: 3-hydroxy-3-methylglutayl-CoA; HMGCR: HMG-CoA reductase; iPSC: induced pluripotent stem cells; IRDs: inherited retinal diseases; KO: knockout; LCA: Leber congenital amaurosis; NMD: nonsense-mediated mRNA decay; OCT: optical coherence tomography; PMBCs: peripheral blood mononuclear cells; POS: photoreceptor outer segments; PTCs: premature termination codons; Rab GGTase: Rab geranylgeranyl transferase; REP: Rab escort protein; RPE: retinal pigment epithelium; TRIDs: translational read-through inducing drugs; WPRE: woodchuck post-transcriptional regulatory element."
10.	Messenger RNA (mRNA)IBA 01/01/2020 - "To analyze CHM mRNA splicing outcomes in 2 unrelated patients with the same c.940+3delA CHM splice site variant identified as mildly affected from a previous study of patients with choroideremia. " 01/01/2020 - "This anomalous mRNA production is related to typical choroideremia phenotype. " 01/01/2020 - "This can be interrogated by exploring the association between messenger RNA (mRNA) levels and phenotype in mildly affected patients with choroideremia. " 01/01/2020 - "Association of Messenger RNA Level With Phenotype in Patients With Choroideremia: Potential Implications for Gene Therapy Dose." 11/01/2020 - "Due to the limited availability of mRNA analysis data, the number of exonic variants resulting in splicing impairment is underestimated although aberrant splicing correction is a promising therapeutic option to treat monogenic diseases, including choroideremia (CHM), a rare X-linked eye disorder arising from sequence alteration of the CHM gene. "

Therapies and Procedures

1.	Therapeutics 01/01/2019 - "AAV gene replacement therapy is the most promising treatment strategy for choroideremia, that has developed exponentially over the last few years with a phase III clinical trial now underway. " 01/01/2018 - "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. " 06/05/2023 - "Adeno-associated viral gene therapy has demonstrated some benefit in clinical trials for choroideremia. " 11/01/2020 - "An 84-year-old man was referred with clinical diagnosis of choroideremia and possible inclusion into a gene therapy trial. " 08/30/2023 - "Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy, affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, with no approved therapy. "
2.	Injections 01/01/2022 - "To use adaptive optics scanning light ophthalmoscopy (AOSLO) to assess the short-term integrity of the cone mosaic following subretinal injections of adeno-associated virus vector designed to deliver a functional version of the CHM gene (AAV2-hCHM) in patients with choroideremia. " 07/01/2013 - "Subretinal injections of AAV2/2-CBA-REP1 into CHM mouse retinas led to a significant increase in a- and b-wave of ERG responses in comparison to sham-injected eyes confirming that AAV2/2-CBA-REP1 is a promising vector suitable for choroideremia gene therapy in human clinical trials." 06/01/2021 - "This case highlights the role of OCTA in diagnosis of choroidal neovascularization in choroideremia as well as its successful management with anti-VEGF injections with long term follow up."
3.	Investigational Therapies (Experimental Therapy) 01/12/2021 - "Update on Gene Therapy Clinical Trials for Choroideremia and Potential Experimental Therapies." 09/01/2017 - "Although much has been written to define the phenotype and genotype of choroideremia (CHM), research continues to provide new insights that serve to better understand its pathogenesis and the directions for potential experimental therapies. "
4.	Semiconductor Lasers 05/01/2015 - "Major innovations in retina include: (1) advances in the treatment of diabetic macular edema, including the use of aflibercept and sustained delivery dexamethasone intravitreal implants as well as subthreshold micropulse diode laser therapy; (2) reduced progression of age-related macular degeneration (AMD) using zinc, vitamin C, vitamin E, lutein, and zeaxanthin supplements as reported in the Age-Related Eye Disease Study-2; (3) use of enhanced-depth imaging optical coherence tomography for choroidal imaging; (4) use of gene therapy to treat choroideremia; (5) use of combination pharmacotherapy (i.e., squalamine + ranibizumab) and gene therapy to treat the neovascular complications of AMD; and (6) use of stem cell-derived retinal pigment epithelium transplants to treat atrophic AMD and Stargardt macular dystrophy. "
5.	Drug Therapy (Chemotherapy) 05/01/2015 - "Major innovations in retina include: (1) advances in the treatment of diabetic macular edema, including the use of aflibercept and sustained delivery dexamethasone intravitreal implants as well as subthreshold micropulse diode laser therapy; (2) reduced progression of age-related macular degeneration (AMD) using zinc, vitamin C, vitamin E, lutein, and zeaxanthin supplements as reported in the Age-Related Eye Disease Study-2; (3) use of enhanced-depth imaging optical coherence tomography for choroidal imaging; (4) use of gene therapy to treat choroideremia; (5) use of combination pharmacotherapy (i.e., squalamine + ranibizumab) and gene therapy to treat the neovascular complications of AMD; and (6) use of stem cell-derived retinal pigment epithelium transplants to treat atrophic AMD and Stargardt macular dystrophy. "