The road to treatment 16

In October we had the pleasure of speaking with Neurophth Therapeutics, a Chinese company developing a gene therapy for ADOA. Recently, Australia's Therapeutic Goods Administration (TGA) approved this program as a drug candidate for clinical investigation, which is necessary to test the drug in ADOA patients. A similar clinical trial approval is also underway in China and the United States, and Neurophth plans to start the study in 2024. The initial study will validate its safety and effectiveness in ADOA patients.

In ADOA, the OPA1 gene, responsible for the production of OPA1 proteins necessary for the normal functioning of mitochondria (the energy reactors in cells), is mutated. If the OPA1 protein does not function properly, the retinal ganglion cells (RGCs, nerve cells behind the eye) will be the first to be affected because they require a lot of energy (ATP) to send the signal from the eyes to the brain. When the mitochondria are damaged, the cells cannot function properly, leading to cell death and eventual vision loss. In most people, this condition usually progresses slowly, but it can also progress much more abruptly and cause very serious symptoms in childhood.

Based on previous research into a similar disease, Leber's Hereditary Neuropathy (LHON), Neurophth has developed an eye injection with a recombined virus (rAAV2) that contains a correct genetic sequence of the OPA1 gene. The medicine is administered with a so-called intravitreal injection into the eye fluid behind the lens, which is a fairly common and safe procedure. The virus can travel from the eye fluid and enter the RGCs. There the virus can produce the necessary proteins and repair the mitochondria. So if the mitochondrial damage is fairly recent and the majority of RGCs are still alive, the remaining RGCs can act as "gene factories" and contribute to vision improvements. However, this drug cannot regenerate RGCs that are already dead.

There are two types of ADOA, the haploinsufficiency and the double-negative mutation (the gene from only one parent is damaged, or from both). This drug from Neurophth is designed for patients who have one gene that is not functioning properly.

Overall, this is an exciting development in the field of gene therapy and offers hope for potential treatment options for ADOA patients in the future, and we will continue to monitor the latest developments!