A UK clinical stage biotech company, NightstaRx, has announced the enrolment of the first patient in a Phase I / II gene therapy study for the treatment of X-linked retinitis pigmentosa (RP). RP is one of the most common retinal dystrophies affecting approximately 1 in 4,000 of the population, while the X-linked form is estimated to account for approximately 8% of RP cases. The company has reported that in March of this year, a 29-year old UK patient became “the first patient with X-linked retinitis pigmentosa to undergo gene therapy”. The surgery, performed at Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, was undertaken by Professor Robert MacLaren.
An ophthalmology research group, headed by Professor MacLaren, worked on a reprogrammed version of the RPGR gene (retinitis pigmentosa GTPase regulator gene) to make the construct more stable, while maintaining its native function. The RPGR gene harbors multiple G and A repeats making it particularly challenging to clone and manipulate in the lab. To stabilize the therapeutic gene the researchers inserted mostly C nucleotides into the construct prior to AAV packaging. The current trial is understood to be the first in the world to test a treatment for retinitis pigmentosa caused by errors in RPGR and is aiming to recruit approximately 20 to 30 patients.
Commenting on the clinical milestone, Prof. MacLaren, Professor of Ophthalmology at the University of Oxford, and an academic founder and board member of NightsaRx, said, “The effect of RPGR-related disease on families with retinitis pigmentosa is devastating and we have spent many years working out how to develop this gene therapy. Changing the genetic code is always undertaken with great caution, but the new sequence we are using has proven to be highly effective in our laboratory studies.”