Research news roundup – innovation in 2022

Retina UK-funded discovery leads to $2.5 million grant

In August, we were proud to share the news that Prof Alison Hardcastle, lead investigator on our UK Inherited Retinal

Disease Consortium (UKIRDC) project, had received a $2.5 million grant from US-based Foundation Fighting Blindness to build on her discovery of a new disease mechanism for RP17.

In 2020, Prof Hardcastle and colleagues at UCL Institute of Ophthalmology, alongside collaborators at Radboud UMC in the Netherlands, published their ground-breaking discovery that RP17 is caused by complex structural re-arrangements of chromosome 17. That research was made possible by Retina UK as the major funder of the UKIRDC.

The researchers have now used the discovery as a springboard to success in the extremely competitive Foundation Fighting Blindness grant round. The new award will enable them to spend five years making a full exploration of underlying disease mechanisms and possible treatment strategies for RP17.

Drug repurposing

Back in March, we reported that early stage clinical trials were underway to test whether drugs already in use for cancer and alcoholism might be helpful in treating retinitis pigmentosa (RP).

Methotrexate is a powerful drug already used to treat certain types of cancer and autoimmune disease, but scientists have also discovered that it can improve the function of faulty rhodopsin protein. Rhodopsin plays a key role in enabling light sensitivity in rod photoreceptors. US biotechnology company Aldeyra Therapeutics has started a small clinical trial of methotrexate for autosomal dominant RP caused by a particular mutation in the rhodopsin gene, with the drug being injected into the jelly of the eyeball.

Meanwhile, knowledge of the biochemical targets of a drug normally used to treat alcoholism has led scientists to investigate whether it might be helpful in retinal disease. The drug, called disulfiram, helped restore some vision in mice with retinal degeneration, by dampening down nerve signal ‘interference’ from dying photoreceptors. The US-based scientists are planning a small clinical trial in people with advanced RP.

Gene therapy without the specificity?

The gene therapies in development today are nearly always only suitable for those whose sight loss is caused by a particular genetic fault. However, with over 300 different genes potentially responsible for inherited retinal conditions, that leaves a huge number in our community without an option within reach.

Two biotechnology companies are now investigating the possibility of supplying the retina with gene therapies that may help overcome degeneration no matter what the causative gene.

US company Sparing Vision is focusing its efforts on preserving

cone photoreceptors, which are concentrated in the centre of the retina and are responsible for detailed vision. Their treatment provides copies of the genetic instructions for making a substance called Rod-derived Cone Viability Factor, (RdCVF), which nourishes cone cells and is essential for their survival. In late 2022, Sparing Vision will begin early phase trials.

Meanwhile, a company called Ocugen is hoping that one particular gene, called NR2E3, might have the power to stabilise retinal cells that have been damaged by a number of different underlying genetic faults. NR2E3 is what’s known as a modifier gene, which can significantly affect disease progression and severity by influencing key biological networks. Studies in five unique mouse models of retinal degeneration, all with different genetic faults, showed that boosting the amount of NR2E3 gene in the retina rescued photoreceptors from further damage. Ocugen has now started in-human testing in the USA.

Gene therapy for X-linked RP

In June, biotechnology company MeiraGTx announced encouraging news from its phase 1/2 clinical trial of a gene therapy aimed at X-linked RP caused by faults in the RPGR gene.

The primary aim of a phase 1/2 clinical trial is to establish the safety of the treatment. The therapy was found to be generally safe and well-tolerated.

In addition, MeiraGTx has announced that trial participants given the treatment experienced significant improvements in their retinal sensitivity and vision compared to untreated ‘control’ participants.

MeiraGTx has now proceeded to a phase 3 trial, which will gather the larger amount of data needed to clearly establish the risk-benefit profile for the treatment. If the outcome is positive, it will enable the company to apply to regulators for licensing.

More information on X-linked inheritance can be found in our Unlock Genetics resource.