Exciting developments for new treatment research

After all, the only available disease-modifying treatment is a gene therapy: known as Luxturna, it works by providing retinal cells with healthy copies of the affected gene, in this case the RPE65 gene.

Update 6 January 2022

Towards the end of 2021, jCyte announced additional findings from the phase 2 trial that help to clarify the circumstances in which the treatment has the most potential. These findings suggest that the treatment provides hope for a significant proportion of those living with RP.

The trial data has shown that people with RP with a central visual field diameter greater than 20 degrees (before treatment) experienced a significant positive response to the jCell injection. This aligns with the earlier news that trial participants with a greater retinal thickness experienced the best results. jCyte’s scientists believe that jCell’s potential for restoring the function of cone photoreceptors, which are responsible for seeing fine detail and colour, is dependent on there being sufficient surviving rod photoreceptors nearby. Cones rely on rods to supply them with an important substance called Rod derived Cone Viability Factor, and the density of rods is high in the area of retina corresponding to a visual field diameter between 20 and 45 degrees.



However, this can only work for people whose sight loss is caused by faults in RPE65, and they probably number well under 100 in the UK. There are other such therapies in the clinical trials pipeline, for genes including RPGR (X-linked RP), USH2A (Usher syndrome type 2) and CNGB3 (achromatopsia), but inherited retinal conditions can be caused by faults in any one of around 300 genes. And of course we know that around 30% of our community do not get a result from a diagnostic genetic test, because the gene causing their sight loss is not yet identified or fully understood. What about the rest of our community? Do they need to wait for a therapy that targets their specific gene? Can they be treated successfully? There is good reason to be hopeful. Research on one gene-specific therapy inevitably produces learning that is relevant to other genes, helping accelerate progress. Several researchers and companies are looking at ways to enhance survival of retinal cells without targeting a specific gene.


For example, in spring 2021, the US company jCyte announced encouraging results from their successful phase 2b clinical trial of jCell, a stem cell-based treatment for RP that is not dependent on a particular genetic fault.

jCell is a proprietary preparation of retinal progenitor cells. These are stem cells that have only just started on the path towards developing into mature, fully differentiated retinal cells. The jCyte treatment involves injecting a dose of several million of these cells into the vitreous (jelly) of the eyeball, with a local anaesthetic.

jCyte do not expect their stem cells to integrate into the retina and replace degenerated photoreceptors. Instead, their rationale is that jCell will provide nourishment and support, by way of substances called trophic factors, to slow degeneration and improve survival in the remaining retina. It would therefore be expected that this approach would work best when there is still some relatively healthy retina left, and would not be successful if the retina was completed degenerated. This was borne out in the results of the trial; the best outcomes, in terms of reasonable improvement in visual acuity, visual field, and low light vision, were seen in people with the greatest retinal thickness before treatment, as measured by OCT scans.

jCyte will now move forward to a larger phase 3 trial, which will recruit participants with a certain minimum retinal thickness, who have the best chance of responding well to the treatment. We will be keeping an eye out for a start date for this trial, although there may not be any UK trial centres. Once it gets going, the trial will probably take a couple of years.


Another company, ReNeuron, is still at the phase 2 trial stage with a slightly different stem cell approach that involves injecting the cells underneath the retina under general anaesthetic. We hope to hear more from them in 2022 about whether this trial is successful.


For those at a later stage of sight loss, an exciting technology called optogenetics holds promise. Some of you may remember seeing a BBC news story in spring 2021, about this type of treatment partially restoring the sight of a man living with retinitis pigmentosa in France (‘Algae proteins partially restore man’s sight’, BBC News, 24 May 2021). The man, who had no remaining vision, first noticed improvement when he realised he could make out the painted stripes of a zebra crossing.

Optogenetics involves providing cells in the retina that don’t normally sense light, but are unaffected by the disease process, with genetic instructions for building light sensitive proteins. These cells can then respond to light and send simple images to the brain. This could provide limited perception of objects, perhaps restoring some independent mobility to a person with severe sight loss.

At the moment, optogenetics is at a fairly early stage of clinical development for retinal degeneration; the news from France provided ‘proof of principle’ that this particular optogenetics approach, developed by the company GenSight Biologics, could work in people with RP.

GenSight Biologics has now initiated an early stage clinical trial. The treatment does require use of a pair of heavy, quite bulky ‘goggles’ to enhance light detection, which may need refining for day-to-day use. Other companies and research groups are also exploring different optogenetics strategies.

Inflammation and retinal degeneration

Meanwhile, those of you who attended our September webinar will have heard Dr Roly Megaw from the University of Edinburgh talking about his work on inflammation and retinal degeneration.

No matter what the causative gene in inherited retinal conditions, the affected retinal cells will ultimately degenerate. Roly is investigating the mechanisms underlying cell death to see if there is a common pathway that could be targeted. He has found that the degenerating cells trigger certain inflammatory processes, and there are drugs already in use for other inflammatory and neurodegenerative diseases that could potentially help slow deterioration of the retina. Roly pointed out that drugs could be used alongside gene therapies, and the most effective treatment regimes could eventually involve multiple approaches combined.

Research grant funding

It’s encouraging to know that researchers and industry are exploring so many avenues in the search for treatments. The grant applications that will be considered in our current research funding round include some projects investigating gene independent therapeutic approaches, while others look at gene-specific strategies. We have only been able to consider these applications thanks to your generous ongoing support.