The eye is a tempting target for researchers developing innovative stem cell and gene therapies. It is small, easily accessible, biologically well understood and transparent, so the effect of treatment can be evaluated non-invasively.

It is also “immune privileged” to some extent, meaning genetically different cells are less likely to be rejected than in most other tissues. Since we have two eyes, furthermore, the ophthalmologist can carry out a procedure on one while leaving the other untreated as a basis for comparison.

A growing need exists for better treatments. Millions of people worldwide have lost some or all of their sight through diseases ranging from the common age-related macular degeneration (AMD) and diabetic retinopathy to a host of rare genetic conditions.

The Cell and Gene Therapy Catapult, set up by the UK government to promote the technology, says ophthalmology is the most popular field for pre-clinical cell and gene therapy research, accounting for 14 out of 60 UK studies in all areas. These experimental therapies are judged to be three years or less from starting clinical trials in patients.

Six cell and gene therapies for the eye are already in the clinic in the UK out of a total of 57 trials, making ophthalmology the third most popular area for clinical study behind cancer and neurology.

Cell therapy involves the injection of new cells to repopulate a retina depleted by disease. Gene therapy aims to restore the function of existing cells by correcting genetic defects.

No ophthalmic gene or stem cell therapy has yet received full marketing approval anywhere in the world. Most advanced, says a recent review by researchers at the University of Massachusetts, is Spark Therapeutics based in Philadelphia. Spark’s lead product treats Leber’s congenital amaurosis 2 (LCA2), a form of retinal degeneration caused by a defect in a gene called RPE65. It uses adeno-associated virus (AAV), which infects humans without causing disease, to carry a functioning copy of the RPE65 gene into retinal cells.

Optogenetics, conceptual artwork. Optogenetics is the integration of optical and genetic systems to control precisely defined events within specific cells of living tissue. The techniques used are precise enough to keep pace with functioning and intact biological systems.
Optogenetics: tests offer hope to thousands of people © Getty

If the final phase of clinical trials confirms the improvements shown in earlier patients, the RPE65 product could be approved and launched in 2017. It “is expected to become the first approved gene therapy product [of any sort] in the US, marking a pivotal step for the entire gene therapy field”, notes the University of Massachusetts review.

While Spark is developing gene therapy for the liver and central nervous system as well as the eye, NightstaRx, a UK biotech company spun out of Oxford university in 2014, concentrates on ophthalmology. It, too, uses AAV, the most popular vector for gene therapy, to carry a correct copy of a defective gene into retinal cells.

London-based NightstaRx’s lead product delivers a type of the REP1 gene to treat choroideremia, an inherited form of progressive blindness. A study of six patients, published this year in the New England Journal of Medicine, found that the therapy maintained or improved vision in the treated eye while the untreated eye continued to deteriorate.

The commercial appeal of ophthalmic gene therapy was shown last month when Allergan, the Dublin-based pharmaceutical group, bought RetroSense Therapeutics, a private Michigan company, for $60m cash and the promise of future milestone payments.

RetroSense is pioneering the clinical application of optogenetics — making cells in the eye sensitive to light. Its RST-001 experimental therapy delivers the ChR2 gene to make retinal ganglion cells respond to light, compensating for the loss of natural photoreceptor cells in degenerative eye disease. The approach is being tested on patients with retinitis pigmentosa, which affects some 100,000 people in the US.

Cell therapy has attracted more public attention than gene therapy for the eye, because stem cells — and embryonic stem cells in particular — are more newsworthy than genetic vectors, even though far fewer patients have received them in clinical trials.

An early stem cell pioneer was Advanced Cell Technology of the US. It changed its name in 2014 to Ocata and was acquired in February 2016 by Astellas, the Japanese pharmaceuticals group, which is continuing its ophthalmic programme on a fairly small scale.

In the UK, the London Project to Cure Blindness launched a clinical trial in September 2015 of a stem cell treatment for wet AMD at Moorfields Hospital in a partnership with the UCL Institute of Ophthalmology and Pfizer, the US drug company. Patches of new retinal pigment epithelial (RPE) cells, derived from embryonic stem cells, have been transplanted into the eyes of two patients to replace those lost in AMD.

Professor Pete Coffey of University College London, co-leader of the project, says clinical results from the first two patients will be published soon and he hopes the trial will be extended to ten people, as originally planned. Pfizer says more cautiously that there are “no current plans to enrol additional patients in this trial”.

The next UK clinical trial of ophthalmic cell therapy may come from Professor Alan Stitt at Queen’s University Belfast, working with the Cell and Gene Therapy Catapult and Scottish Blood Transfusion Service. His team is generating “endothelial progenitor cells” from umbilical cord blood. These would restore the vasculature (network of blood vessels) within the retina, which goes wrong in ischemic eye disease.

“In ophthalmology we need to move on from trying to treat end-stage disease,” says Prof Stitt. “We want to use these new therapies to treat earlier and better, to prevent blindness.”

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