GenSight Biologics is developing GS010, a therapy that causes ND4, a mitochondrial protein, to be expressed in the nucleus and shuttled to the mitochondria. This concept of moving mitochondrial DNA into the nucleus, where it is better protected, is a key approach for combating mitochondrial dysfunction, one of the hallmarks of aging. The company has taken GS010 into Phase 3 clinical trials for the treatment of Leber Hereditary Optic Neuropathy (LHON), a disease that causes blindness.
This company has had some issues with clinical trials in the past, as each patient had a single treated eye to test the efficacy of GS010 and the other eye was left untreated to serve as the control group. The problem was that administering this therapy seemed to affect the untreated eye along with the treated eye, leading to a lack of difference between the experimental group and the control group – thus possibly making an effective therapy seem ineffective.
GenSight is also developing GS030, a gene therapy that allows retinal cells to detect the presence of light.
As of December 2020, the Phase 3 clinical trial was a success and represents the moment when mitochondrial gene therapy is now a reality in humans. The researchers report that by week 96 of the study, 25 participants showed a significant improvement of best-corrected visual acuity in at least one eye compared to the baseline taken before treatment. 29 of the 37 participants showed an improvement of vision in both eyes. They discovered that eyes were about three times more likely to regain 20/200 vision or better following treatment.
An expanded clinical trial is slated to happen as a follow-up, if the results remain positive it is likely to be approved and enter healthcare use for treating LHON. The researchers are also interested in using the same approach to treat other mitochondrial diseases.