REGENERATE (REP1 Gene Replacement Therapy) Trial: Version 1.0
Research type
Research Study
Full title
An open label Phase 2 clinical trial of retinal gene therapy for choroideremia using an adeno-associated viral vector (AAV2) encoding Rab-escort protein 1 (REP1)
IRAS ID
179453
Contact name
Robert MacLaren
Contact email
Sponsor organisation
University of Oxford
Eudract number
2015-001383-18
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Research Summary
Choroideremia is an incurable genetic disease that causes blindness in men. The disease is caused by a defect in a certain gene located on the X-chromosome, and this is why the disease affects men and women differently. Women have two X-chromosomes and so a normal gene on one X-chromosome can compensate for a defective gene on the other X-chromosome to some extent. Men, however, only have one X-chromosome.
In choroideremia, this defective gene results in a progressive degeneration of the retina, which is like a camera film that lines the back of the eye. Sight loss in choroideremia begins with ‘night blindness’ (i.e. loss of night vision) in adolescence, followed by a gradual loss of peripheral vision which results in progressively worsening ‘tunnel vision’. Ultimately, central vision is lost by the fourth or fifth decade.
There are currently no effective treatments available for choroideremia, but we have developed a new technique of gene therapy which we believe may help to slow or even stop the degeneration. The new technique involves putting normal copies of the affected gene back into the cells of the retina to help them to function normally. This is achieved by an operation to inject the normal genes into the retina, using a modified virus to carry the genes into the cells.
The purpose of this study is to find out if we can preserve vision in patients suffering from choroideremia by replacing the defective gene using gene therapy. This Phase 2 study is the continuation of an earlier Phase 1 study which commenced in 2011, and which has shown encouraging results so far.
Summary of Results
: Choroideremia is a rare eye disease caused by a defective gene that prevents the cells in the retina, the light sensitive layer at the back of the eye, from functioning normally. The disease usually affects males, although females who carry the genetic mutation can also develop the disease. In childhood, choroideremia patients initially experience ‘night blindness’, or difficulty in seeing in low light. As the disease progresses, there is a gradual loss in the peripheral vision, eventually resulting in ‘tunnel vision’ and finally in complete blindness by late adulthood.
The aim of this study was to investigate if gene therapy was able to prevent further vision loss in patients suffering from choroideremia. The gene therapy for choroideremia uses a modified non-pathogenic virus, called a viral vector, to carry copies of genes with the correct code into the retinal cells, to replace the defective genes and thereby help the cells to function normally. Thirty male participants from two eye hospitals took part in the study. Each participant received gene therapy in one eye, with the other eye left untreated for purposes of comparison. The condition and function of the treated and untreated (control) eyes were then monitored at regular time points over a 24-month period.
As the rate of retinal deterioration in choroideremia patients is very slow, a meaningful difference in the comparative rate of vision loss in the treated and control eyes was not observed during the 24-month assessment period of this study. Four participants experienced worse vision in their treated eyes; including one case of sight loss caused by severe inflammation that did not respond to medication. Additional data is being collected in a follow-on observational study to track the long-term progress of retinal degeneration in the treated eyes and control eyes of the participants.REC name
London - West London & GTAC Research Ethics Committee
REC reference
15/LO/1379
Date of REC Opinion
16 Oct 2015
REC opinion
Further Information Favourable Opinion