A recent paper, published in Science, explored the use of optic gene therapy to treat Leber’s Hereditary Optic Neuropathy. Surprisingly, researchers were able to improve vision in both eyes, despite only one being treated.
What is LHON?
Leber’s Hereditary Optic Neuropathy (LHON) is a mitochondrially inherited condition. Around 1 in 30,000 people are affected globally, mostly males in their 20s or 30s. Transmitted from a mother to her children, it is the most common form of mitochondrial blindness. LHON attacks the retinal ganglion cells, damaging the optic nerves and thus causing acute or subacute loss of central vision.
Optic Gene Therapy
The treatment involved an experimental form of optic gene therapy. In a phase-III clinical trial, 37 patients were treated with a modified viral vector in one eye only. Tailored genetic information was injected into the eye to counteract the activity of defective or malfunctioning genes. For this specific therapy, the MT-ND4 gene was targeted.
The replacement of this gene via gene therapy appeared to rescue the retinal ganglion cells from their fate. The therapy led to an average improvement in vision of 15 letters on the standard ETDRS chart (you may have used one at your local opticians). The therapy was most effective for those at the earlier stages of LHON.
Incredibly, although only one eye was treated, vision in both eyes improved in 78% of patients in the trial. This result was totally unanticipated by the scientists.
The researchers have stressed how life changing the success of this trial may be for those affected by LHON. Generally, individuals lose their vision rapidly over the course of weeks and less than 20% of patients regain their sight. Beyond vision restoration, this gene therapy could potentially be generalised to other mitochondrial diseases and has exciting implications for future treatments.
Although it is currently unclear why and how the gene therapy spread from one eye to the other, follow up studies have suggested the injected viral vectors can spread via interocular diffusion. Further research will be needed to fully understand the mechanisms at play.