Gene therapy uses harmless viruses to deliver healthy copies of the affected gene into retinal cells, with the aim of preserving visual function; this is the principle behind Luxturna, a treatment for Leber congenital amaurosis caused by faults in the RPE65 gene, which is the first treatment for inherited retinal disease to be made available on the NHS. However, the RPGR gene has an unusual genetic code, which makes it unstable to work with in the laboratory and until recently difficult to translate into a usable treatment.
Scientists at the University of Oxford reprogrammed the genetic code of the RPGR gene to make it more stable, providing the basis for this new gene therapy.
The international trial, led by Professor Robert MacLaren, was sponsored by Biogen Inc., with support from the NIHR Oxford Biomedical Research Centre. Eighteen patients in total were treated with increasing doses of the virus carrying an RPGR gene in which the DNA had been altered to increase stability, but in a manner that still allowed correct production of the missing RPGR protein. The treatment is delivered via injection into the back of the eye under general anaesthetic.
The early results from the study showed that the treatment was safe, and six patients who received mid-range doses of the therapy had unexpected improvements in their peripheral vision beginning as early as one month after the treatment. The research team’s full findings are published in the journal Nature Medicine.
One of Prof MacLaren’s patients, Kurtis Lonie, said: “When my mum spotted the trial in an RNIB newsletter I felt so hopeful about what I was reading. At this stage in my life I was struggling deeply with what I thought my life would become. The speed of my condition’s degeneration was unknown so I had no choice but to apply and do whatever I could to hopefully help others in the future, as well as myself.”
After undergoing tests and screening, Kurtis was given the choice of which eye he wanted to be treated, and he opted for the one with worse vision.
“About a month after the treatment my vision was beginning to return in the treated eye. The sharpness and depth of colours I was slowly beginning to see were so clear and attractive. My visual field exploded and I could see so much more at once than ever before in that eye. Before long, the eye was undoubtedly better than the untreated eye.
“The results have been nothing short of astonishing and life changing for me, I really hope this trial is approved and they can treat what once was my better eye.”
Can I have this treatment?
This treatment is only relevant for people with X-linked RP caused by mutations in the RPGR gene. It will not work for other X-linked genes such as RP2.
The treatment is still at the clinical trial stage, so can only be given at trial centres to those who meet a number of participation criteria; the researchers will need to continue to gather trial data before the treatment can be approved by regulatory authorities.
If you have a diagnosis of X-linked RP and you are interested in joining the trial, ask your GP or local ophthalmologist to refer you to Prof Robert MacLaren at the Oxford Eye Hospital, part of the Oxford University Hospitals NHS Foundation Trust. The team at Oxford will then need to assess your eligibility before they can enrol you in the trial.