Progress,Gene,Therapy,Heredita health Progress of Gene Therapy in Hereditary Optic Nerve Injury an


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Optic neuropathies are a class of neurodegenerative diseases caused by various reasons such as hypoxia, inflammation, poisoning, nutritional deficiencies, glaucoma, compression, trauma, hereditary and congenital diseases. Although the causes of optic neuropathy have their own characteristics, they will eventually lead to the death of optic ganglion cells (RGCs).The axons emitted by RGCs form the optic nerve. The regeneration of RGCs is restricted by many exogenous and endogenous factors. The exogenous constraints are mainly the microenvironment that inhibits neuron regeneration after axon damage. The endogenous constraints are mainly the lack of ability of mature RGCs to grow and regenerate after injury. Therefore, damage to the optic nerve is often difficult to repair.Leber's hereditary optic neuropathy (LHON) is a hereditary optic neuropathy caused by point mutations in mitochondrial DNA. The most common sites for point mutations are bases 11778, 14484, and 3460, and gene therapy has a better effect on hereditary optic neuropathy caused by a single gene mutation.Adeno-associated viruses type 2 (AAV2) is relatively safe with high efficiency in transferring to the inner layer of the retina, and low risk of tumor formation, making it a commonly used vector for gene therapy. In clinical studies, there have been studies using intravitreal injection of recombinant AAV2 vector carrying ND4 (rAAV2-ND4) in order to restore normal expression or function of genes in RGCs.In a study involving 9 patients with severely impaired vision, the researchers treated these 9 patients with rAAV2-ND4. Before treated, the patients were observed for 12 months and no spontaneous recovery was found. After 3 to 6 months of treatment, the patients’ vision began to improve, and at 9 months after treatment, 7 of 9 patients had their best-corrected visual acuity (BCVA) restored to 0.3. The visual field index of 7 patients improved after treatment (1 patient did not improve, and 1 patient refused to perform a visual field test).Some researchers underwent unilateral eye gene therapy for 9 similar patients, and followed up within 36 months of treatment. Among them, the BCVA of 2 patients’ treated eyes improved, but the condition worsened after 6 months. The BCVA of untreated eyes improved after 36 months. One patient's bilateral vision was improved after treatment but returned to the pre-treatment level after 12 months; the vision of the 2 patients who did not receive treatment gradually recovered to 0.2 by themselves. The visual field index of both treated and untreated eyes of 4 patients decreased in 6 months after treatment; the visual field index of 2 patients gradually recovered.The results of these studies indicate that gene therapy has at least a short-term benefit, but the long-term effect is not significant, which may because the expression of genes transferred by gene therapy gradually decreases over time.The biggest challenge faced by the new technology and new target of gene therapy is how to accurately regenerate neurons, and how to make them accurately link with the original neural tissue. Studies have shown that many regenerative neurons appear tortuous in the optic nerve and even regenerate in the opposite direction."Now, it is unclear whether these erroneously regenerated neurons can link to the optic nerve and thus produce erroneous visual functions," said a senior scientist at Creative Biolabs, a leading service provider of gene therapy. "Non-viral vector gene therapy with low toxicity but limited efficiency may have a certain therapeutic effect, but this treatment method has not been applied to the treatment of hereditary optic nerve diseases."Targeted gene therapy for hereditary optic nerve diseases has shown certain therapeutic effects in animal model experiments of optic nerve damage and early human experiments. However, there are still some problems that need to be solved, and scientists worldwide are trying to unveil more secret of genomes. Article Tags: Hereditary Optic Nerve, Hereditary Optic Neuropathy, Visual Field Index, Gene Therapy, Hereditary Optic, Optic Nerve, Optic Neuropathy, After Treatment, Visual Field, Field Index, Improved After

Progress,Gene,Therapy,Heredita

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