Sci. Transl. Med. 12, eaaz7423 (2020)
The injection of a gene-therapy treatment for Leber hereditary optic neuropathy (LHON) into only the right eye of patients with LHON resulted in the unexpected improvement of sight in both eyes.
LHON is a monogenic hereditary mitochondrial DNA neuropathy that results in bilateral vision loss for which there is limited treatment. However, gene-therapy strategies are being developed in which the therapeutic protein product is translocated into the mitochondria through a mitochondrial targeting sequence.
Sahel and colleagues carried out a randomized double-masked, sham-controlled phase 3 trial of one such therapy (AAV2/2-ND4) in 37 patients with LHON. For those who were given the treatment, the authors injected the therapy into the right eye only and treated the left with a sham therapy. They found that this therapy induced an improvement in a least one eye in 25 participants and that 29 participants had improvement in both eyes. This was surprising; however, the authors found a plausible mechanistic explanation in a further nonhuman primate study.