EyeWorld India December 2020 Issue

NEWS & OPINION 60 EWAP DECEMBER 2020 disease (Oxford Biomedica/ Sanofi), and Usher syndrome (Oxford Biomedica/ Sanofi) as under clinical investigation. He also said gene augmentation is being studied for X-linked recessive disorders, such as choroideremia (Biogen, Spark Therapeutics) and retinitis pigmentosa (AGTC, Biogen, MeiraGTx), and mitochondrially inherited disorders such as Leber hereditary optic neuropathy (GenSight). Iveric Bio is working on a “knockdown and replace” strategy to treat autosomal dominant retinitis pigmentosa. Gene therapy to treat more commonly occurring wet AMD is in development as well. Dr. Ciulla said REGENXBIO is developing a ranibizumab-like anti-VEGF protein for subretinal delivery, and Adverum is creating an aflibercept-like anti- VEGF for intravitreal delivery. For dry AMD, Hemera Biosciences is developing HMR59 to produce the protein CD59 that blocks the final step of the complement cascade, Dr. Ciulla explained. “These have potential to be very important therapies because they could provide long-lasting benefits to reduce treatment burden, but the clinical trials are still underway. We have to assess for inflammation and durability, whether they completely alleviate the need for further treatment in most patients or decrease the need for injections, which would be valid as well. We will also need to determine which patients benefit most,” Dr. Ciulla said. Takeaways At this point, Dr. Sohn said the important thing for general and anterior segment ophthalmologists to know about gene therapy treatment is that there is currently only one FDA- approved treatment, though several are in trials. “Accurate testing is very important for patients with inherited retinal diseases because they may have a disease that can be treated with an FDA-approved treatment or qualify for a trial for a non- RPE65-mediated inherited retinal disease,” Dr. Sohn said. Categories of gene therapy • Gene augmentation: Adding a gene to a cell • Gene editing: Revising the existing genetic code • Gene inactivation: Silencing a gene, often a dominant negative one • Selective toxicity: Introducing “suicide” genes and immune sensitization, as in chimeric antigen receptor (CAR)-T cells to recognize cancer cells • RNA therapeutics: Targeting RNA instead of DNA within the gene Source: Thomas Ciulla, MD “With that comes the very important responsibility of understanding what the doctor is seeing on exam to identify a patient with an inherited retinal condition. Educating oneself about what these diseases look like on exam and by history and when to send these patients for testing or to an inherited eye disease specialist is of utmost importance.” Dr. Sohn said his colleague Edwin Stone, MD, PhD, developed an educational website with images and videos of inherited retinal disease conditions, StoneRounds.org, to help provide ophthalmologists with a reference for inherited retinal diseases. “Education is extremely important for the physician because if you just send the patient for genetic testing, the doctor needs to explain that to the patient. To know what to test a patient for, how to interpret the test, and communicate this effectively to the patient and family are crucial,” Dr. Sohn said. Timing is also important for effective gene therapy, Dr. Sohn said. Patients need to still have functional cells for a gene therapy to be effective. If cells are no longer functional, that’s where a stem cell therapy could come into play. EWAP Editors’ note: Dr. Ciulla is a Volunteer Clinical Professor of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, and has interests with Clearside Biomedical. Dr. Sohn is Associate Professor of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, and has interests with Oxford Biomedica. ADVERTISER LISTING Alcon Page 7 www.alcon.com Feather Page 39 www.feather.co.jp/en Johnson & Johnson Vision Page 2, 40 www.jjvision.co Oculus Page 13 www.corneal- biomechanics.com Zeiss Page 18-21 www.zeiss.com ASCRS Page 63 www.ascrs.org APACRS Page 5, 32, 42, 57, 64 www.apacrs.org