Research round-up, spring 2023

Progress towards treatments for inherited retinal conditions continues to gather pace and there’s been lots going on in the last few months, with more and more approaches being explored. This round-up gives a flavour of the variety of developments, including plenty that are not specific to a particular genetic fault.

OCU400 from Ocugen

Biotechnology company Ocugen has announced positive preliminary safety and efficacy results from its phase 1/2 trial in adults with RP and LCA caused by faults in the NR2E3 and RHO genes. Ocugen’s therapy, known as OCU400, is a novel gene therapy approach that doesn’t just target one specific genetic cause of disease. Instead, it relies on providing copies of a “modifier gene” that can influence the expression of multiple genes and gene networks. It could potentially be used to treat sight loss with a wide range of genetic causes.

The early results are based on the effects seen in seven trial participants, and suggest that the treatment has a good safety profile. In addition, OCU400 appeared to improve or stabilise participants’ ability to navigate a maze in low light, as well as improve ability to read letters on an eye chart.

Ocugen has now widened the trial to include adults affected by Leber congenital amaurosis (LCA) caused by the CEP290 gene, and children affected by mutations in NR2E3, RHO and CEP290. The company will continue to monitor participants to gather long-term data before deciding whether to proceed to a phase 3 trial, which could include European centres.

EA-2353 from Endogena Therapeutics

Meanwhile, Endogena Therapeutics is also exploring an innovative approach that could have broad applicability. They have developed a drug that can potentially activate retinal stem and progenitor cells lying dormant in the eye. These cells could then develop into mature photoreceptors to support some restoration of vision.

The treatment, currently called EA-2353, is at the first stage of clinical testing, which will primarily establish its safety and tolerability. This study involves 14 people with RP in the USA, who are receiving the drug via injection into the eyeball. Early data suggests there are no serious side effects, so Endogena will now also start to make preliminary assessments of efficacy.

Transcorneal electrical stimulation from OkuVision

Another approach that could be appropriate for a large proportion of the Retina UK community is transcorneal electrical stimulation, which involves a device rather than a drug, and relies on the theory that electrical stimulation may induce a neuroprotective effect on retinal cells. This is being explored by German company OkuVision; their OkuStim device includes electrodes that are placed on the lower eyelid in contact with the eyeball, and can be used at home, in weekly 30-minute stints, after training from an ophthalmologist.

OkuStim was trialled several years ago at University Eye Hospital Tubingen (Germany) in around 50 people with RP, demonstrating good safety and tolerability. The results of that study have recently been reanalysed, and suggest that OkuStim can slow visual field loss, with the size of the effect correlating with the amplitude of the current used. OkuStim is currently undergoing a much larger trial within the German public health service, and this study should provide definitive evidence, within the next couple of years, as to whether the treatment can have a significant effect. If so, OkuVision hopes to persuade the NHS to make OkuStim widely available in the UK.

OkuStim is not the same as Fedorov Restoration Therapy – listen to our recent podcast on unproven treatments to find out more:

Condition-specific research

Leber congenital amaurosis (LCA)

Moving to condition-specific research, there have been a couple of exciting findings in the laboratories of researchers investigating LCA caused by faults in the CEP290 gene. US researchers found that an old blood-pressure drug called reserpine appears to support photoreceptor survival in cell and animal models of this condition. They also found four other promising drug candidates in a screen of around 6,000 compounds previously approved to treat other conditions. This “drug repurposing” approach is potentially an extremely efficient and cost-effective way to find new treatments.

Meanwhile, here in the UK, former Retina UK grantee Prof Mike Cheetham and his team at UCL Institute of Ophthalmology found that a plant-derived substance called eupatilin, belonging to a group of compounds called flavonoids, improved aspects of photoreceptor structure in a number of cell-based models of CEP290 LCA.

Stargardt disease

Moving to Stargardt disease, Intergalactic Therapeutics has announced that it has made progress in developing a gene therapy to deliver healthy copies of the Stargardts gene, ABCA4, into the retina. Like a number of other retinal disease genes, including USH2A, ABCA4 is very large and doesn’t fit inside the virus-based packaging systems most commonly used for gene therapy. Intergalactic Therapeutics has successfully used a non-viral system to deliver gene therapy into the eyes of pigs modelling Stargardt disease. The company now intends to gather the data it needs to enable it to apply for permission to begin studies in humans.

There are plenty of other studies and clinical trials underway around the world. As always, we will report any significant developments – you can keep up to date via our e-news, Look Forward magazine, website, webinars and podcasts.