Scientists from Sirius make a breakthrough in treating inherited blindness

Scientists from the Sirius University of Science and Technology have improved the approach to gene therapy for Leber's hereditary optic neuropathy. This is a severe disease in which a person rapidly loses vision. The research results are published in the journal Frontiers in Bioengineering and Biotechnology.

One of the main causes of the disease is a breakdown in the mitochondrial gene MT-ND4. Because of it, retinal cells produce less energy, cellular stress accumulates in them, and calcium metabolism is disrupted. As a result, these cells gradually die. Ganglion cells of the optic nerve are especially vulnerable, so a person can quickly lose central vision, often without the possibility of restoring it.

Editing mitochondrial DNA directly is very difficult: mitochondria are protected by a double membrane, there can be hundreds of them in one cell, and each contains several copies of DNA. Therefore, scientists use a workaround. A working copy of the damaged mitochondrial gene is transferred to the cell nucleus, where the necessary protein is synthesized, after which it must be delivered back to the mitochondria, where it should function.

In the new study, Sirius specialists tested five options for delivering the protein to mitochondria. Such sequences act as an "address": they help the protein get to where it should act. The MTS-cox8k variant worked best. In the cell model, it reduced the level of reactive oxygen species by 72%, the amount of calcium in mitochondria by 47%, and increased the mitochondrial membrane potential by 38%. This means that the cells experienced less stress, and their energy metabolism was partially restored.

Next, the technology is planned to be tested on neuronal models, retinal ganglion cells from induced pluripotent stem cells of patients, and on animals. Currently, the development is at the preclinical stage.

Existing treatments, including idebenone, can only partially slow the progression of the disease and rarely restore lost vision. The new approach should target the molecular cause of the disease – the impaired function of the ND4 protein in mitochondria.