Gene therapies for retinal dystrophies: potential in the Chinese population
Keywords:
Choroideremia, Color vision defects, Gene therapy, Leber congenital amaurosis, Night blindness, congenital stationary, Retinitis pigmentosaAbstract
Retinal dystrophies (RD) refer to a group of clinically and genetically heterogenous degenerative conditions of the retina. We aim to summarize emerging gene therapies for RD and their efficacy in restoring photoreceptor or bipolar cell functions. In patients with retinitis pigmentosa, injection of adeno-associated virus containing RPE65, RPGR or MERTK results in improvements in outcomes of the multi-luminal mobility test and full-field light sensitivity threshold test. In animal models of congenital stationary night blindness, gene augmentation of Cacn1f, LRIT3 or Nyx increases ON-bipolar cell signaling cascade and preserves retinal morphology. Patients with achromatopsia show improved visual acuity, contrast sensitivity, and cone responses after injection of a vector comprising CNGA3 or CNGB3. In patients with Leber congenital amaurosis, administration of a vector containing RPE65 or RDH12 results in improved full-field sensitivity to white light and photoreceptors responses, particularly in pediatric populations. Some patients have improved dark-adapted spectral sensitivities and pupillary light responses after injection of vectors. For choroideremia, REP1 gene therapy has been shown to improve visual acuity and retinal sensitivity. Nonetheless, voretigene neparvovec-ryzl (Luxturna) remains to be the only approved gene therapy in patients with biallelic RPE65 mutation. In the Chinese population, RPGR, Lrit3, Nyx, CNGA3, RPE65, RDH12, and CHM gene therapies may be beneficial, because the mutated genes are compatible to the genes investigated in previous clinical trials. A thorough understanding of gene therapies for different RD subtypes may allow more personalized management of retinal degeneration.
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