更新于：2024-11-01

Achromatopsia 3

全色盲3型

更新于：2024-11-01

基本信息

别名

ACHM 3、ACHM1, FORMERLY、ACHM3

+ [18]

简介-

关联

项与全色盲3型相关的药物

Entacingene turiparvovec (MeiraGTx)

靶点

CNGB3

作用机制

CNGB3基因刺激剂

在研机构

Janssen Pharmaceutica NV [+1]

原研机构

MeiraGTx UK II Ltd.

在研适应症

色觉障碍 [+1]

非在研适应症

全色盲3型

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与全色盲3型相关的临床试验

NCT03758404 / Completed临床1/2期

An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/8-hG1.7p.coCNGA3) for Gene Therapy of Children and Adults With Achromatopsia Owing to Defects in CNGA3

A clinical trial of adeno-associated virus vector (AAV) CNGA3 retinal gene therapy for patients with achromatopsia

开始日期2019-08-12

申办/合作机构

MeiraGTx UK II Ltd.

[+1]

NCT03001310 / Completed临床1/2期

An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/8-hCARp.hCNGB3) for Gene Therapy of Adults and Children With Achromatopsia Owing to Defects in CNGB3

A clinical trial of AAV - CNGB3 retinal gene therapy for patients with achromatopsia

开始日期2017-01-16

申办/合作机构

MeiraGTx UK II Ltd.

[+1]

100 项与全色盲3型相关的临床结果

登录后查看更多信息

100 项与全色盲3型相关的转化医学

登录后查看更多信息

0 项与全色盲3型相关的专利（医药）

登录后查看更多信息

项与全色盲3型相关的文献（医药）

2023-09-01·American journal of ophthalmology

First-in-Human Gene Therapy Trial of AAV8-hCARp.hCNGB3 in Adults and Children With CNGB3-associated Achromatopsia.

Article

作者: Berry, Pamela ; Wong, Sui Chien ; Robson, Anthony G ; Capuano, George ; Zaman, Serena ; Bainbridge, James ; Fleck, Penny ; Georgiou, Michalis ; Lu, Wentao ; Naylor, Stuart ; Dong, Xiangwen ; Anglade, Eddy ; Forbes, Alexandria ; Thiadens, Alberta ; Henderson, Robert H ; Kalitzeos, Angelos ; Besirli, Cagri G ; Hirji, Nashila ; Kumaran, Neruban ; Michaelides, Michel ; Ripamonti, Caterina ; Gottlob, Irene ; Georgiadis, Anastasios ; Smith, Alexander J ; Ali, Robin R ; Kane, Thomas

PURPOSETo assess the safety and efficacy of AAV8-hCARp.hCNGB3 in participants with CNGB3-associated achromatopsia (ACHM).DESIGNProspective, phase 1/2 (NCT03001310), open-label, nonrandomized clinical trial.METHODSThe study enrolled 23 adults and children with CNGB3-associated ACHM. In the dose-escalation phase, adult participants were administered 1 of 3 AAV8-hCARp.hCNGB3 dose levels in the worse-seeing eye (up to 0.5 mL). After a maximum tolerated dose was established in adults, an expansion phase was conducted in children ≥3 years old. All participants received topical and oral corticosteroids. Safety and efficacy parameters, including treatment-related adverse events and visual acuity, retinal sensitivity, color vision, and light sensitivity, were assessed for 6 months.RESULTSAAV8-hCARp.hCNGB3 (11 adults, 12 children) was safe and generally well tolerated. Intraocular inflammation occurred in 9 of 23 participants and was mainly mild or moderate in severity. Severe cases occurred primarily at the highest dose. Two events were considered serious and dose limiting. All intraocular inflammation resolved following topical and systemic steroids. There was no consistent pattern of change from baseline to week 24 for any efficacy assessment. However, favorable changes were observed for individual participants across several assessments, including color vision (n = 6/23), photoaversion (n = 11/20), and vision-related quality-of-life questionnaires (n = 21/23).CONCLUSIONSAAV8-hCARp.hCNGB3 for CNGB3-associated ACHM demonstrated an acceptable safety and tolerability profile. Improvements in several efficacy parameters indicate that AAV8-hCARp.hCNGB3 gene therapy may provide benefit. These findings, with the development of additional sensitive and quantitative end points, support continued investigation.

2023-08-01·Current Biology

Seeing color following gene augmentation therapy in achromatopsia

Article

作者: Marks Ohana, Devora ; Nahmany, Einav ; Banin, Eyal ; McKyton, Ayelet ; Levin, Netta

How will people who spent their visual lives with only rods respond to cone function restoration? Will they be able suddenly see the colors of the rainbow? CNGA3-achromatopsia is a congenital hereditary disease in which cone dysfunction leads patients to have rod photoreceptor-driven vision only in daylight,¹^,²^,³^,⁴ seeing the world in blurry shades of gray.⁵^,⁶ We studied color perception in four CNGA3-achromatopsia patients following monocular retinal gene augmentation therapy.⁷^,⁸^,⁹ Following treatment, although some cortical changes were reported,³^,⁴ patients did not report a dramatic change in their vision.³^,⁹ However, in accordance with the fact that sensitivity of rods and cones is most different at long wavelengths, they consistently reported seeing red objects on dark backgrounds differently than they did before surgery.³ Because clinical color assessments failed to find any indication of color vision, we conducted a gamut of tailored tests to better define patients' descriptions. We evaluated patients' perceived lightness of different colors, color detection, and saliency, comparing their treated with their untreated eyes. Although the perceived lightness of different colors was generally similar between the eyes and matched a rod-input model, patients could detect a colored stimulus only in their treated eyes. In a search task, long response times, which were further extended with array size, suggested low saliency. We suggest that treated CNGA3-achromatopsia patients can perceive a stimulus's color attribute, although in a manner that is different and very limited compared with sighted individuals. We discuss the retinal and cortical obstacles that might explain this perceptual gap.

2020-11-25·Translational Vision Science & Technology3区 · 医学

Intraobserver Repeatability and Interobserver Reproducibility of Foveal Cone Density Measurements in CNGA3- and CNGB3-Associated Achromatopsia

3区 · 医学

ArticleOA

作者: Georgiou, Michalis ; Kane, Thomas ; Kalitzeos, Angelos ; Michaelides, Michel ; Litts, Katie M ; Singh, Navjit ; Patterson, Emily J ; Carroll, Joseph ; Dubra, Alfredo ; Hirji, Nashila

PurposeTo examine repeatability and reproducibility of foveal cone density measurements in patients with CNGA3- and CNGB3-associated achromatopsia (ACHM) using split-detection adaptive optics scanning light ophthalmoscopy (AOSLO).MethodsThirty foveae from molecularly confirmed subjects with ACHM, half of whom harbored disease-causing variants in CNGA3 and half in CNGB3, underwent nonconfocal split-detection AOSLO imaging. Cone photoreceptors within the manually delineated rod-free zone were manually identified twice by two independent observers. The coordinates of the marked cones were used for quantifying foveal cone density. Cone density and difference maps were generated to compare cone topography between trials.ResultsWe observed excellent intraobserver repeatability in foveal cone density estimates, with intraclass correlation coefficients (ICCs) ranging from 0.963 to 0.991 for CNGA3 and CNGB3 subjects. Interobserver reproducibility was also excellent for both CNGA3 (ICC = 0.952; 95% confidence interval [CI], 0.903-1.0) and CNGB3 (ICC = 0.968; 95% CI, 0.935-1.0). However, Bland-Altman analysis revealed bias between observers.ConclusionsFoveal cone density can be measured using the described method with good repeatability and reproducibility both for CNGA3- and CNGB3-associated ACHM. Any degree of bias observed among the observers is of uncertain clinical significance but should be evaluated on a study-specific basis.Translational RelevanceThis approach could be used to explore disease natural history, as well as to facilitate stratification of patients and monitor efficacy of interventions for ongoing and upcoming ACHM gene therapy trials.