Optic neuropathies are a type of neurodegenerative disorders caused by multiple causes, such as hypoxia, inflammation, poisoning, deficiency in nutrition, glaucoma, stress , trauma, inherited and congenital disorder. While the causes of optic neuropathy have their own characteristics, optic ganglion cells (RGCs) will ultimately die. Optic nerve is generated by the axons produced by RGCs. A number of exogenous and endogenous factors hinder the regeneration of RGCs. The exogenous constraints are primarily the microenvironment that inhibits regeneration of the neurons after axon damage. The endogenous constraints are primarily that mature RGCs lack the capacity to expand and regenerate after injury. Therefore, it is also impossible to repair damage to the optic nerve. Learn more about MSK Therapy & Injury Management.
Hereditary optic neuropathy (LHON) from Lebar is an inherited optic neuropathy caused by point mutations in mitochondrial DNA. Bases 11778, 14484, and 3460 are the most common sites for point mutations and gene therapy has a greater effect on inherited optic neuropathy triggered by a single gene mutation.
Adeno-associated type 2 viruses (AAV2) are fairly healthy, with high effectiveness in spreading to the inner layer of the retina, and low risk of tumour development, making it a widely used gene therapy vector. Studies using intravitreal injection of recombinant AAV2 vector carrying ND4 (rAAV2-ND4) to restore normal expression or gene function in RGCs have been performed in clinical trials.
The researchers identified those 9 patients with rAAV2-ND4 in a study involving 9 patients with significant vision loss. The patients were monitored for 12 months before being treated, and there was no spontaneous recovery. Vision of the patients started to improve after 3 to 6 months of treatment, and at 9 months after treatment, 7 out of 9 patients had their best-corrected visual acuity (BCVA) restored to 0.3. After diagnosis, the visual field index of 7 patients improved (1 patient did not improve and 1 patient declined to do a visual field test).
For 9 similar patients, several researchers underwent unilateral eye gene therapy, and followed up within 36 months of diagnosis.