Experimental therapy of One Eye may Improve vision in other in hereditary disease

Leber hereditary optic neuropathy (LHON) is caused by mutations in mitochondrial DNA (mtDNA). It is the most common form of mitochondrial blindness, transmitted from a mother to her children that attacks the retinal ganglion cells, damaging the optic nerves. Around 1 in 30,000 people are thought to be affected, usually men in their 20s or 30s. Gene therapy using adeno-associated viral (AAV) vectors is a promising strategy for monogenic blinding diseases. On a previous pre-clinical trial recombinant AAV, rAAV2/2-ND4 has shown therapeutic effects in a mouse model of LHON. Based on these findings researchers conducted a phase 3 trial in patients with LHON and treated one eye with recombinant AAV. Although one eye was treated the authors reported unexpected sustained vision improvement in both eyes. Investigative analysis in nonhuman primates showed evidence of viral vector DNA transfer from the injected to the contralateral eye.

REVERSE was a randomized, double-blinded, placebo-controlled, multicentric phase 3 clinical trial that evaluated the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). Researchers included 37 subjects carrying the m.11778G>A (MT-ND4) mutation and with a duration of vision loss between 6 to 12 months. Patient's right eye was randomly assigned to receive treatment with either rAAV2/2-ND4 (GS010) or placebo injection and the left eye received the treatment not allocated to the right eye. Patients were scheduled for 96 days follow-up. The major outcome assessed was the difference in the change in BCVA from baseline to week 48 between the two treatment groups.