Keeping an Eye on Gene Therapy
The Editors of Eye and Gene Therapy have put together this joint collection on gene therapy in the eye, to showcase some of the recent research in this field.
There has been a surge of gene therapy trials in Ophthalmology that include gene replacement, gene editing and gene silencing. The eye is an immunoprivileged organ and the retinal photoreceptors and retinal pigment epithelium are key target cells for gene therapy to treat several inherited retinal diseases. In 2017, for the first time, subretinal voretigene neparvovec-rzyl gene therapy was approved by U.S. Food and Drug Administration for treatment of a rare ophthalmic condition called Leber congenital amaurosis that is caused by mutations of RPE65.1 Very recently, encouraging safety and clinical outcomes of subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR) has been reported for x-linked retinitis pigmentosa, a more common condiiton.2 Several trials are also on-going in age related macular degeneration, the most common cause of visual impairment in the elderly. The modes of delivery of the gene therapies are also evolving from the more complex subretinal and suprachoridal approach to intravitreal therapy. Another exciting area in the field of gene therapy is to aid disease modification, axon regeneration and neuroprotection in the field of glaucoma and optic nerve disorders, the conditions previously believed to be irreversible once neuronal damage occurs.3 However, despite the advantages that the eyes have over other organs, gene therapy is challenging especially because measuring subtle improvements following gene therapy in these conditions with very poor visual potential require validation of novel clinical end-points. The rapid progress made in this field in the last few years is exciting and encouraging especially when it rewards the most needy patients with their vision.
1: Prado DA, Acosta-Acero M, Maldonado RS. Gene therapy beyond luxturna: a new horizon of the treatment for inherited retinal disease. Curr Opin Ophthalmol. 2020 May;31(3):147-154. doi: 10.1097/ICU.0000000000000660. PubMed PMID: 32175942.
2: Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, Nanda A, Davies A, Wood LJ, Salvetti AP, Fischer MD, Aylward JW, Barnard AR, Jolly JK, Luo E, Lujan BJ, Ong T, Girach A, Black GCM, Gregori NZ, Davis JL, Rosa PR, Lotery AJ, Lam BL, Stanga PE, MacLaren RE. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med. 2020 Mar;26(3):354-359. doi: 10.1038/s41591-020-0763-1. Epub 2020 Feb 24. PubMed PMID: 32094925; PubMed Central PMCID: PMC7104347.
3. Khatib TZ, Martin KR. Protecting retinal ganglion cells. Eye (Lond). 2017 Feb;31(2):218-224.
