Biodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue Molecular Therapy - Methods and Clinical Development Année : 2021

Biodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates

Résumé

Lenadogene nolparvovec (Lumevoq) gene therapy was developed to treat Leber hereditary optic neuropathy (LHON) caused by the m.11778G > A in MT-ND4 that affects complex I of the mitochondrial respiratory chain. Lenadogene nolparvovec is a replication-defective, single-stranded DNA recombinant adeno-associated virus vector 2 serotype 2, containing a codonoptimized complementary DNA encoding the human wildtype MT-ND4 subunit protein. Lenadogene nolparvovec was administered by unilateral intravitreal injection in MT-ND4 LHON patients in two randomized, double-masked, and sham-controlled phase III clinical trials (REVERSE and RESCUE), resulting in bilateral improvement of visual acuity. These and other earlier results suggest that lenadogene nolparvovec may travel from the treated to the untreated eye. To investigate this possibility further, lenadogene nolparvovec was unilaterally injected into the vitreous body of the right eye of healthy, nonhuman primates. Viral vector DNA was quantifiable in all eye and optic nerve tissues of the injected eye and was detected at lower levels in some tissues of the contralateral, noninjected eye, and optic projections, at 3 and 6 months after injection. The results suggest that lenadogene nolparvovec transfers from the injected to the noninjected eye, thus providing a potential explanation for the bilateral improvement of visual function observed in the LHON patients.
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Dates et versions

hal-03416686 , version 1 (05-11-2021)

Identifiants

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David J Calkins, Patrick Yu-Wai-Man, Nancy J Newman, Magali Taiel, Pramila Singh, et al.. Biodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates. Molecular Therapy - Methods and Clinical Development, 2021, 23, pp.307 - 318. ⟨10.1016/j.omtm.2021.09.013⟩. ⟨hal-03416686⟩
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