Molecular Mechanisms Governing Sight Loss in Inherited Cone Disorders
Abstract
1. Introduction
2. Achromatopsia
2.1. CNGB3 and CNGA
2.2. PDE6C and PDE6H
2.3. GNAT2
2.4. ATF6
2.5. Animal Models
3. Xp28-Associated Disorders
3.1. Blue-Cone Monochromatism
Animal Models
3.2. Bornholm Eye Disease
Animal Model
4. Cone and Cone–Rod Dystrophies
4.1. ABCA4
4.2. PRPH2
4.3. RPGR
4.4. Animal Model
5. Gene Therapies
NCT Number | Study Title | Interventions | Phases | Start Date | Completion Date | Study Status |
---|---|---|---|---|---|---|
CNGA3 | ||||||
NCT02610582 | Safety and Efficacy of rAAV.hCNGA3 Gene Therapy in Patients With CNGA3-linked Achromatopsia | rAAV.hCNGA3—gene therapy | PHASE1|PHASE2 | November 2015 | June 2027 | Active |
NCT03278873 | Long-Term Follow-Up Gene Therapy Study for Achromatopsia CNGB3 and CNGA3 | AAV—CNGA3—gene therapy | PHASE1|PHASE2 | 29 June 2017 | 4 April 2024 | Completed—no results published |
NCT03758404 | Gene Therapy for Achromatopsia (CNGA3) | AAV—CNGA3—gene therapy | PHASE1|PHASE2 | 12 August 2019 | 10 June 2021 | Completed—results published [98] |
NCT02935517 | Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial) | AGTC-402—gene therapy | PHASE1|PHASE2 | 3 August 2017 | August 2026 | Active |
CNGB3 | ||||||
NCT02599922 | Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial) | rAAV2tYF-PR1.7-hCNGB3—gene therapy | PHASE1|PHASE2 | 11 April 2016 | July 2026 | Active |
NCT03278873 | Long-Term Follow-Up Gene Therapy Study for Achromatopsia CNGB3 and CNGA3 | AAV—CNGB3—gene therapy | PHASE1|PHASE2 | 29 June 2017 | 4 April 2024 | Completed—no results published |
NCT03001310 | Gene Therapy for Achromatopsia (CNGB3) | AAV—CNGB3—gene therapy | PHASE1|PHASE2 | 16 January 2017 | 25 October 2019 | Completed—results published [96] |
RPGR | ||||||
NCT04794101 | Follow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene | AAV5-hRKp.RPGR—gene therapy | PHASE3 | 4 December 2020 | 19 December 2029 | Active |
NCT03316560 | Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations | rAAV2tYF-GRK1-RPGR—gene therapy | PHASE1|PHASE2 | 16 April 2018 | March 2025 | Active |
NCT05874310 | Gene Therapy for Subjects With RPGR Mutation-associated X-linked Retinitis Pigmentosa | FT-002—gene therapy | EARLY_PHASE1 | 1 February 2023 | 1 November 2027 | Recruiting |
NCT06275620 | A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN) | AGTC-501—gene therapy | PHASE2 | 14 November 2023 | August 2029 | Enrolling |
NCT04671433 | Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated with Variants in the RPGR Gene | AAV5-hRKp.RPGR—gene therapy | PHASE3 | 4 December 2020 | 20 September 2024 | Active |
NCT04850118 | A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP | rAAV2tYF-GRK1-hRPGRco G | PHASE2|PHASE3 | 14 March 2024 | October 2029 | Recruiting |
NCT04517149 | 4D-125 in Patients With X-Linked Retinitis Pigmentosa (XLRP) | 4D-125—gene therapy | PHASE1|PHASE2 | 9 June 2020 | May 2029 | Active |
NCT03584165 | Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa | BIIB111/BIIB112—gene therapy | PHASE3 | 4 June 2018 | 4 June 2026 | Enrolling |
NCT03252847 | Gene Therapy for X-linked Retinitis Pigmentosa (XLRP)—Retinitis Pigmentosa GTPase Regulator (RPGR) | AAV2/5-RPGR—gene therapy | PHASE1|PHASE2 | 14 July 2017 | 18 November 2021 | Completed—no results published |
NCT05926583 | A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa | AAV5-hRKp.RPGR—gene therapy | PHASE3 | 12 September 2023 | 9 October 2029 | Recruiting |
NCT03116113 | A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112 | BIIB112—gene therapy | PHASE1|PHASE2 | 8 March 2017 | 18 November 2020 | Completed—Results Published [85] |
NCT06333249 | A Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (SKYLINE) | rAAV2tYF-GRK1-RPGR—gene therapy | PHASE2 | 13 April 2021 | February 2027 | Active |
ABCA4 | ||||||
NCT01367444 | Phase I/IIA Study of SAR422459 in Participants With Stargardt’s Macular Degeneration | SAR422459—EIAV-ABCA4 gene therapy | PHASE1|PHASE2 | 8 June 2011 | 16 August 2019 | Terminated due to adverse effects [94,95] |
NCT06300476 | Safety and Efficacy of a Single Subretinal Injection of JWK006 Gene Therapy in Subjects With Stargardt Disease (STGD1) | JWK006—AAV-ABCA4 gene therapy | PHASE1|PHASE2 | 20 November 2023 | 30 December 2029 | Active |
Clinical Heterogeneity
6. Conclusions
7. Limitations of the Review
Funding
Conflicts of Interest
References
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Brotherton, C.; Megaw, R. Molecular Mechanisms Governing Sight Loss in Inherited Cone Disorders. Genes 2024, 15, 727. https://doi.org/10.3390/genes15060727
Brotherton C, Megaw R. Molecular Mechanisms Governing Sight Loss in Inherited Cone Disorders. Genes. 2024; 15(6):727. https://doi.org/10.3390/genes15060727
Chicago/Turabian StyleBrotherton, Chloe, and Roly Megaw. 2024. "Molecular Mechanisms Governing Sight Loss in Inherited Cone Disorders" Genes 15, no. 6: 727. https://doi.org/10.3390/genes15060727
APA StyleBrotherton, C., & Megaw, R. (2024). Molecular Mechanisms Governing Sight Loss in Inherited Cone Disorders. Genes, 15(6), 727. https://doi.org/10.3390/genes15060727