Related Experiment Video
Updated: Jan 20, 2026
Isolation of Next-Generation Gene Therapy Vectors through Engineering, Barcoding, and Screening of Adeno-Associated Virus AAV Capsid Variants
Published on: October 18, 2022
Efficacy and Safety of Retinal Gene Therapy Using Adeno-Associated Virus Vector for Patients With Choroideremia: A
M Dominik Fischer1,2,3,4, G Alex Ochakovski1,2, Benjamin Beier3
1University Eye Hospital, University of Tübingen, Tübingen, Germany.
Importance:
Choroideremia (CHM) is a rare, degenerative, genetic retinal disorder resulting from mutation of the CHM gene, leading to an absence of functional ras-associated binding escort protein 1 (REP1). There is currently no approved treatment for CHM.
Objective:
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.
Design, Setting, And Participants:
Tübingen Choroideremia Gene Therapy (THOR) was a single-center, phase 2, open-label randomized clinical trial. Data were collected from January 11, 2016, to February 26, 2018. Twenty-four-month data are reported for 6 men with a molecularly confirmed diagnosis of CHM. Intention-to-treat analysis was used.
Interventions:
Patients received AAV2-REP1 by a single, 0.1-mL subretinal injection of 1011 genome particles during vitrectomy into 1 eye randomly assigned to receive treatment.
Main Outcomes And Measures:
Primary end point was change in best-corrected visual acuity (BCVA) on the Early Treatment Diabetic Retinopathy Study chart from baseline to month 24 in the treated eye vs the control eye. Secondary end points included microperimetry variables, change in fundus autofluorescence, and spectral-domain optical coherence tomographic evaluations from baseline to month 24 in the treated eye vs the control eye.
Results:
On enrollment, the mean (SD) age of the 6 men included in the study was 54.9 (4.1) years. The mean (SD) BCVA score was 60.3 (13.4) (approximately 20/63 Snellen equivalent) in the study eyes and 69.3 (20.6) (approximately 20/40 Snellen equivalent) in the control eyes. At 24 months, the BCVA change was 3.7 (7.5) in the treated eyes and 0.0 (5.1) in the control eyes (difference, 3.7; 95% CI, -7.2 to 14.5; P = .43). Mean change in retinal sensitivity was 10.3 (5.5) dB in the treated eyes and 9.7 (4.9) dB in the control eyes (difference, 0.6; 95% CI, -10.2 to 11.4; P = .74). A total of 28 adverse events were reported; all were consistent with the surgical procedure (eg, conjunctival hyperemia, foreign body sensation), and none were regarded as severe.
Conclusions And Relevance:
Among 6 participants, gene therapy with AAV2-REP1 was associated with maintenance or improvement of visual acuity, although no significant difference was found from control eyes. All safety issues were associated with the surgical procedure and none were judged severe. Continued investigations could more precisely define the efficacy and safety of gene therapy with AAV2-REP1 in CHM.
Trial Registration:
ClinicalTrials.gov identifier: NCT02671539.
Insights
Gene therapy using AAV2-REP1 showed potential for maintaining or improving vision in choroideremia patients, though results were not significantly different from control eyes. Safety concerns were linked to surgery, not the gene therapy itself.
Area of Science:
- Ophthalmology
- Genetics
- Retinal Degeneration
Background:
- Choroideremia (CHM) is a rare genetic retinal disorder caused by CHM gene mutations, leading to loss of REP1 protein.
- Currently, no approved treatments exist for choroideremia, highlighting the need for therapeutic interventions.
Purpose of the Study:
- To evaluate the safety and efficacy of AAV2-REP1 gene therapy for treating choroideremia.
- To assess the delivery of a functional CHM gene via an adeno-associated virus vector (AAV2) in patients with CHM.
Main Methods:
- A phase 2, open-label, randomized clinical trial (THOR) involving 6 male participants with confirmed CHM.
- Participants received a single subretinal injection of AAV2-REP1 in one eye, with data collected over 24 months.
Main Results:
- The study assessed changes in best-corrected visual acuity (BCVA) and retinal sensitivity over 24 months.
- While treated eyes showed some maintenance or improvement in BCVA, the difference compared to control eyes was not statistically significant.
- Adverse events were predominantly related to the surgical procedure and were not severe.
Conclusions:
- AAV2-REP1 gene therapy was associated with visual acuity maintenance or improvement in CHM patients.
- No significant difference in efficacy was observed between treated and control eyes.
- Further research is warranted to fully determine the efficacy and safety profile of AAV2-REP1 gene therapy for choroideremia.
More Related Videos
Related Concept Videos
09:20Isolation of Next-Generation Gene Therapy Vectors through Engineering, Barcoding, and Screening of Adeno-Associated Virus (AAV) Capsid Variants
06:16Subconjunctival Administration of Adeno-associated Virus Vectors in Small Animal Models
04:53A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
10:14Using Adeno-associated Virus as a Tool to Study Retinal Barriers in Disease
06:48Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
08:36The Adjuvant Efficacy of Angong Niuhuang Pill in the Treatment of Viral Encephalitis: A Meta-Analysis of Randomized Controlled Trials