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Gene therapies in development for monogenic, complex retinal diseases
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WAIKOLOA, Hawaii — Gene therapy for retinal disease is in various stages of development, with more than a dozen retinal clinical trials underway, Elias Reichel, MD, told colleagues at Retina 2019.
For the most part, these trials involve gene replacement using adeno-associated virus (AAV) to deliver the therapy, which thus far has shown persistent expression in humans and no significant safety concerns.
“[Leber’s congenital amaurosis] is the first condition that has been successfully treated with gene therapy,” Reichel said. Luxturna (voretigene neparvovec-rzl, Spark Therapeutics) is the first monogenic gene therapy FDA approved for a retinal condition and is being administered in select practice settings in the U.S. This therapy provides a functioning RPE65 gene that produces RPE65 protein to retinal pigment epithelium cells to compensate for the RPE65 mutation.
However, gene therapy is not limited to use in monogenic diseases, he said. It is also under development for use in complex diseases, such as age-related macular degeneration and diabetic retinopathy.
Gene replacement trials underway are targeting Leber’s congenital amaurosis, choroideremia, X-linked retinitis pigmentosa, X-linked retinoschisis, achromatopsia, other types of retinitis pigmentosa, Stargardt disease, and wet and dry AMD.
One concept for delivering gene therapy for AMD is via intravitreal injection. The virus is injected into the vitreous and from there the virus infects the ganglion cells, creating an annulus of expression around the fovea, which is ideal for macular disorders, according to Reichel.
“With intravitreal injection, what we’re doing is trying to block the membrane attack complex from forming soluble CD59,” he said. – by Patricia Nale, ELS
Reference: Reichel E. Retinal gene therapy. Presented at: Retina 2019; Jan. 20-25, 2019; Waikoloa, Hawaii.
Disclosures: Reichel reports financial relationships with Hemera Biosciences, Nightstar Therapeutics, Regeneron, Spark Therapeutics and Astellas.