May 8, 2024

Research highlights from Association for Research in Vision and Ophthalmology (ARVO) Conference

Fighting Blindness Canada Director of Research and Mission Programs Dr. Larissa Moniz attended the 2024 ARVO meeting in Seattle to learn about the latest in vision research and treatment development. Here are some of the highlights:

1. Improving delivery of gene therapy to make it safer and more effective:

• Currently, most gene therapies being tested for inherited retinal diseases are delivered by a sub-retinal injection. Avista Therapeutics is developing a new way to deliver gene therapy by intravitreal injection (IVT) which could be a less complex surgery than sub-retinal injection.
• One of the current limitations of gene therapy is the size of the mutated gene because the delivery vector can only “hold” a certain size gene. Different research groups are looking at ways to deliver larger genes like Myo7A mutated in USH1B or ABCA4 mutated in Stargardt disease. One of the strategies being tested is to deliver the gene in two parts which reform in the cell to form a single functional gene.

2. Developing cell replacement and protective therapies

• Some of the strategies discussed include using neuroprotective factors from rod photoceptor cells to increase cone photoreceptor cell survival; using organoid retinal sheets to try and restore some light perception for patients with end-stage retinitis pigmentosa; and testing stem cell derived retinal pigment epithelial replacement therapies for dry AMD.
• We also heard from researchers who are part of the rReSTORe consortium. The goal of the consortium is to address challenges to developing a restorative therapy for retinal ganglion cells (RGCs) which are damaged in diseases like glaucoma. Researchers are looking at different aspects of RGC replacement from the initial stages to develop functional RGCs from stem cells to optimizing transplantation models to identifying ways to improve RGC survival once cells are transplanted.

3. There were updates on a number of ongoing clinical trials including for X-linked retinoschisis (XLRS) and Leber congenital amaurosis 5 and 10.

• Atsena therapeutics announced preliminary results from a Phase 1/2 gene therapy for XLRS. The therapy called ATSN-201 is delivered with a sub-retinal injection and uses a special delivery vector that allows the gene therapy to move away from the sight of the injection, hopefully delivering gene therapy to a larger area of the retina. Results from the first three patients treated showed no serious negative effects and early signs that the gene therapy is helping repair some retinal damage. The clinical trial is continuing to enroll patients and test different doses of the therapy.
• Opus Genetics provided an update on their gene therapy trial for LCA5. In the Phase 1/2 clinical trial, patients receiving low doses of the gene therapy did not have any serious side effects and anecdotal evidence suggests patients who were blind at the start of the trial regained some light and object perception. Based on this promising data, the trial will now move on to testing higher doses of the gene therapy.
• Results from a Phase1/2 gene therapy clinical trial for LCA10 caused by CEP290 mutations were published in the prestigious journal, New England Journal of Medicine. The trial, which treated 12 patients, showed that the gene therapy had no serious side effects and 64 per cent of participants showed improvement in at least one vision measurement such as best corrected visual acuity.