Abstract
About this talk
Leber Hereditary Optic Neuropathy (LHON) is a rare, maternally inherited mitochondrial genetic disorder characterized by sudden, painless vision loss. The disease has a significant unmet medical need and is primarily caused by three mitochondrial DNA point mutations: G3460A, G11778A, and T14484C, located in the ND1, ND4, and ND6 genes, respectively. Among them, the m.11778G>A mutation in the ND4 gene is the most common (accounting for 75% of cases) and is associated with the most severe clinical phenotype.
Lenadogene nolparvovec (Lumevoq®) is a gene therapy based on a recombinant adeno-associated viral vector (rAAV2/2) encoding the human wild-type ND4 protein. It is designed to address the root cause of LHON in patients harboring the m.11778G>A mutation by restoring ND4 protein expression, thereby improving mitochondrial Complex I function and protecting retinal ganglion cells.
Three multicenter Phase III clinical trials — RESCUE, REVERSE, and REFLECT — demonstrated sustained, bilateral improvement in Best-Corrected Visual Acuity (BCVA) after unilateral or bilateral intravitreal injection of lenadogene nolparvovec. Across these trials, 189 patients were treated, showing meaningful restoration of visual function.
Early access programs have been initiated in the United States and Europe, underscoring the therapy’s potential to meet a significant therapeutic gap in mitochondrial optic neuropathies.
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