Aug 29, 2023

2023 Inherited Retinal Disease Research Updates

September is Inherited Retinal Disease (IRD) Month and we thought it was a great time to share some of the research discoveries that are moving us towards new treatments across different IRDs and gene mutations. Keep reading to learn more about research updates for cone-rod dystrophy, Leber congenital amaurosis, retinitis pigmentosa, Stargardt disease, Usher syndrome, X-linked retinitis pigmentosa, and X-linked retinoschisis.

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

Cone-rod dystrophy

A new company, Beacon Therapeutics, has launched with a focus on gene therapies for cone-rod dystrophy and X-linked retinitis pigmentosa (learn more below). Beacon will undertake preclinical work on a potential gene therapy for cone-rod dystrophy caused by mutations in the CDHR1 gene. This work was originally started by Dr. Robert MacLaren (University of Oxford) who is a co-founder and adviser to the company. If these studies are successful, Beacon hopes to move the CDHR1 gene therapy to a human clinical trial in the coming years.

Leber congenital amaurosis (LCA)

Last year, we reported that ProQR was stopping their gene editing clinical trials for LCA caused by mutations in the CEP290 gene (sepofarsen) and Usher syndrome. Recently, the company announced that these gene therapy programs have been acquired by the pharmaceutical company Laboratoires Théa. Laboratoires Théa will be creating a team dedicated to IRDs and we will update you as more information on the status of these treatments and trials becomes available.

Retinitis pigmentosa (RP)

• Endogena Therapeutics has completed enrollment for their Phase 1/2a trial ahead of schedule. This trial will test the safety and efficacy of a drug treatment (EA-2353) which aims to activate endogenous stem cells and preserve vision in patients with RP caused by any genetic mutation. The first data from this trial is expected to be reported in 2024.
• PYC Therapeutics has launched a Phase 1 clinical trial to test a gene-editing therapy (VP-001) for RP11 caused by mutations in the PRPF31 gene. The U.S-based trial is aiming to test the therapy for safety and efficacy in 20 patients starting in 2023.
• Aldeyra announced results from a Phase 2 clinical trial testing methotrexate (ADX-2191) as a potential therapy for patients with RP with mutations in rhodopsin that lead to protein misfolding. IRD mutations, including some mutations in the RHO gene, can lead to problems with protein folding that are toxic to photoreceptor cells. In pre-clinical studies, methotrexate helped photoreceptor cells remove misfolded proteins. In this trial, patients received monthly or twice-monthly injections of methotrexate. The treatment was found to be safe and led to improved best corrected visual acuity and low-light visual acuity among other measures. Aldeyra is now discussing the launch of a Phase 2/3 trial.
• Researchers have completed a pre-clinical study for a potential gene therapy for RP caused by mutations in the CNGB1 gene. Injection of the gene therapy into the eyes of dogs with mutations in CNGB1 improved rod photoreceptor cell vision, and helped preserve cone and rod photoreceptor health. It is hoped that the results of this study will lead to a clinical trial in humans.
• RHO gene mutations are a common cause of autosomal dominant RP. In an animal model with the autosomal dominant RHO T17M mutation, researchers used a gene-editing approach to reduce the amount of mutant gene in the cell. This led to improved retinal function and photoreceptor cell health. This study could also be useful for scientists studying other types of autosomal dominant IRDs.
• Researchers have tested a potential FAM161A gene therapy in an animal model of RP caused by mutations in FAM161A. In experiments, the FAM161A gene replacement therapy improved retinal structure and some retinal cell activity in mice with mutations in the FAMI61A gene. While this is promising, further studies will be needed before this therapy can be considered for a human clinical trial.

Stargardt disease

• Belite Bio is testing an oral drug Tinlarebant (LBS-008) in a Phase 3 trial, to see if it slows progression of Stargardt disease. Tinlarebant is designed to lower levels of vitamin-A based toxins. The trial has completed enrollment and results are expected to be announced in 2024.

Usher Syndrome

Last year we reported that ProQR was stopping their gene editing clinical trials for Usher syndrome 2A (ultevursen (QR421a)) and Leber congenital amaurosis. In a recent update the company announced that these gene therapy programs have been acquired by the pharmaceutical company Laboratoires Théa. Laboratoires Théa will be creating a team dedicated to IRDs and we will update you as more information about these therapies and trials becomes available.

X-linked retinoschisis (XLRS)

• Atsena Therapeutics has treated the first patient with XLRS in a Phase 1/2 gene therapy trial. This trial will test the safety of a potential RS1 gene replacement therapy (called ATSN-201). The trial hopes to enroll 18 individuals and data from the trial will be reported in 2024 or 2025.
• Abeona Therapeutics reported preclinical study results for a potential gene therapy for the RS1 gene which is mutated in XLRS. The gene therapy (called ABO-503) improved photoreceptor cell survival and health in a mouse model of XLRS. The company will continue experiments with the goal of bringing this gene therapy to a human clinical trial in the coming years.

X-linked retinitis pigmentosa (XLRP)

A new company, Beacon Therapeutics, has launched with a focus on gene therapies for XLRP and cone-rod dystrophy. Beacon will lead the ongoing Phase 2 clinical trial for the RPGR gene replacement therapy which was acquired from AGTC.

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If you have eye health related questions, please reach out to our Health Information Line at healthinfo@fightingblindness.ca