Lenadogene nolparvovec rAAV2 gene therapy vector encoding ND4 Treatment of Leber hereditary optic neuropathy

Leber hereditary optic neuropathy (LHON) is a maternally inherited, progressive, bilateral optic neuropathy, affecting typically young adults whose visual prognosis remains very poor. There are many currently known genetic variants that can cause the disease. In the last few years, several treatment modalities, including the antioxidant drug idebenone restoring coenzyme Q10 function, have been investigated for LHON management; however, the clinical course and visual recovery in patients with LHON remain limited. As gene therapy has been attracting increasing interest in the field of inherited retinal degenerations in the recent years, lenadogene nolparvovec (GS-010), a novel, recombinant adeno-associated viral vector serotype 2 encoding the wild-type ND4 gene (rAAV2/2-ND4), is currently being examined only for patients with LHON due to the G11778A mutation. In this regard, results from phase Ill RESCUE and REVERSE trials have shown encouraging clinical outcomes in terms of visual function in both the treated and nontreated eyes, along with a good safety profile. Further, larger-scale clinical trials will provide more evidence about GS-010's clinical efficacy for the management of LHON.