Gene Therapy Shows Modest Success for Genetic Blindness
The latest data from a phase 3 clinical trial shows that gene therapy can counter visual degeneration associated with Leber hereditary optic neuropathy (LHON). The therapy, delivered by intravitreal injection, uses an adeno-associated virus vector to deliver a corrected copy of the mutated ND4 mitochondrial gene. LHON is a rare, maternally inherited mitochondrial mutation that can cause blindness, most commonly in young men, though it does not happen in all individuals with the mutation. The condition often starts with blindness in one eye, accompanied or followed shortly by blindness in the second eye. Researchers believe that the injected viral vector gets taken up retinal ganglion cells, where the mutated gene interferes with vision. Once synthesized, a mitochondria-targeting sequence facilitates transport of the protein to the mitochondria.
@dev The mechanism of this counter-intuitive finding remains uncertain, but it is not known that acutely in this disease when people are just starting to lose this vision, during the first couple of months, they get swelling of the axons from these retinal ganglion cells. Hypothesis is that swelling may actually act as a barrier for the drug to get into the retinal ganglion cell bodies themselves and be transfected. So it turns out that earlier may not be better.