Sep 9, 2024

2024 Inherited Retinal Disease Research Updates

September is Inherited Retinal Disease (IRD) Month! Once again, we have compiled IRD research discoveries that took place in the last year. We are always looking to bring you news of innovation and progress so if you’ve missed any of our monthly updates on Leber congenital amaurosis, RP, Stargardt Disease, X-linked RP, X-linked retinoschisis, and Usher syndrome you can catch up on our Research News page or by signing up for our monthly e-newsletter.

Technical Advances

Translational research

• There are different types of gene editing approaches. Gene replacement, CRISPR and one of the newest, prime editing. Prime editing can very precisely change DNA in a way that does less damage to the DNA than CRISPR. In a study published in Nature Biotechnology researchers used a new system that delivered prime editing components and partially restored vision in blind mice. This is potentially the first time that prime editing has achieved a therapeutic effect. This advancement opens the possibility for a new, more precise form of gene editing to be used as a therapy for inherited eye diseases.

Preclinical Research

• UMass Chan Medical School has licensed the rights to commercialize a new minigene therapy vector to Iveric Bio, An Astellas Company. While gene therapy has had some promising successes, the large size of some genes has been a challenge using current delivery vectors. This new vector would allow delivery of shorter versions of a mutated gene and may open the door to new gene therapies for previously hard to treat IRDs (e.g. LCA10 and Stargardt disease).

Retinitis Pigmentosa (RP)

Discovery Research

• Taking place around the world, discovery research is being conducted to better understand how gene mutations lead to vision loss. This information is crucial to develop new therapies. For example, in mice with CERKL mutations, it was found that retinal cells were in a constant state of stress and couldn’t turn on antioxidant responses. In a second study, mice with mutations in the DHDDS gene that cause non-syndromic RP59. This mouse had inner retinal degeneration and reduced retinal response suggesting it will be a useful animal model for further study of this disease.
• A study from scientists at University of California, Irving, have developed an antibody that may be a potential treatment for autosomal dominant RP (adRP) caused by mutations in the Rhodopsin gene. The antibody is a very small molecule called a nanobody. The research team found that this nanobody bound to a specific place on the Rhodopsin protein and stabilized it. They hope that this technology could be further developed as a therapeutic for adRP.

Translational Research

• A study published in Nature Communications showed that a combination of repurposed drugs could slow photoreceptor degeneration in different animal models of RP with different gene mutations. Interestingly, the drugs were only effective in combination, not individually. More studies will need to be done on this combination before a clinical trial in humans can be considered, however it could be a potentially new gene agnostic therapy option. More widely, repurposing drugs could lead to faster and less expensive access to new treatments.

Clinical Research

• Ocugen has announced Health Canada approval to launch Canadian sites for their Phase 3 liMeliGht clinical trial for a gene modifier therapy OCU400. OCU400 will be tested in individuals with RP with mutations in the RHO gene as well as participants with other gene mutations to determine if this is a gene-agnostic therapy that could be useful for many types of gene mutations or types of retinal degeneration. The location of the Canadian trial sites has not been announced yet. Ocugen also recently announced that the US Federal Drug Agency (FDA) has approved access for OCU400, for RP for patients through an expanded access program. Even though the Phase 3 trial is ongoing and the treatment has not been approved by the FDA, access was granted based on promising data from a Phase 1/2 clinical trial.

• Rznomics is starting a Phase 1/2a clinical trial for an RNA editing therapy, RZ-004 for the treatment of autosomal dominant RP. The trial will likely take place in South Korea, and additional details are not available at this time.

• PYC Therapeutics reported results from their Phase 1 PLATYPUS clinical trial for an RNA therapy, VP-001, for people with RP11, caused by mutations in the PRPF31 gene. So far, nine patients have been treated in on eye and no serious side effects were observed. Encouragingly, retinal sensitivity improved in the treated eye. The company is now planning for a larger trial, starting in 2025.

Stargardt Disease

Preclinical research

• SalioGen Therapeutics, a biotechnology company, announced a candidate therapeutic, SGT-1001, that they will be developing towards a clinical trial. SGT-1001, uses a novel approach to deliver large genes, like ABCA4, which is commonly mutated in Stargardt disease. SalioGen is completing preclinical work before applying to the FDA for approval to launch a clinical trial in the coming years.

Clinical Research

• Ascidian Therapeutics has received clearance from the FDA, paving the way for the start of a Phase 1/2 clinical trial in 2024 to test the safety of a potential RNA editing therapy for Stargardt disease.

• Belite Bio presented data from their phase 2 study of the oral drug Tinlarebant for Stargardt disease. Data was reported from 13 adolescent patients treated for 24 months. 42% of patients showed signs of slower or stalled retinal degeneration progression and overall the study suggested a stabilization of visual acuity after taking the daily oral drug. The drug continues to be studied in an ongoing Phase 3 study.

• Ocugen has received approval to test a higher dose in a Phase 1/2 clinical trial for a gene modifier therapy for Stargardt’s disease. The therapy, OCU410ST, was tested in 3 patients initially. Based on a good safety profile, new patients will now receive a higher dose of the drug. The therapy introduces a gene that doesn’t fix the disease-causing mutation but may reduce retinal degeneration by reducing oxidative stress and inflammation.

Usher Syndrome

Clinical Research

• Results from a Phase 1/2 gene therapy trial for patients with Usher syndrome Type-1B (USH1B) showed that while lower doses of the therapy, EIAVMYO7A, were safe, there were some serious side effects in patients who received higher doses. Because of this, the trial, sponsored by Sanofi, was terminated early.

You can learn more about ongoing clinical trials for IRDs on our Clinical Trials webpage.

We are here to answer your questions. If you have questions about research, clinical trials or your eye health reach out to our Health Information Line at healthinfo@fightingblindness.ca or 1-888-626-2995.