Voretigene neparvovec
Indications
Voretigene neparvovec is used for:
VN-rzyl is indicated for the treatment of children and adult patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The administration of VN-rzyl is conditioned to the physician determination of the presence of viable retinal cells.[FDA label] The RPE65 represents the LCA2 form of the Leber's congenital amaurosis (LCA). LCA is a group of inherited conditionts that involves retinal degeneration and severe vision loss in early childhood leading to total blindness by 30-40 years old. The LCA2 form is associated with a mutation that interferes with the isomerohydrolase activity of the retinal pigment epithelium. The isomerohydrolase activity transforms the trans-retinyl esters to 11-cis-retinal which is the natural ligand and chromophore of the opsins of rod and cones photoreceptors. In the presence of RPE65 mutations, the opsins cannot capture light or transduce it into electrical responses to initiate vision.[A31480]
Adult Dose
Child Dose
Renal Dose
Administration
Contra Indications
Precautions
Pregnancy-Lactation
Interactions
Adverse Effects
Side effects of Voretigene neparvovec :
Mechanism of Action
VN-rzyl is designed for the delivery, in the cells of the retina, of a normal copy of the gene encoding for the human retinal pigment epithelial protein whose molecular weight is 65 kDa. The delivery of this gene will allow the production of the RPE65 protein re-establishing the visual cycle and restoring the visual function.[A31480]
The adeno-associated viral vectors (AAVV) presents two open reading frames encoding for its replication (*rep*) and capsid (*cap*). It contains as well a zone with inverted terminal repeats which are required for the replication and packing of the viral genome. The replication of the AAVV requires the presence of a co-infector such as adenovirus or herpesvirus. Thus, without this co-infector, AAVV stays latent with its viral genome in the infected cell. The AAVV construct will contain the transgene in the inverted terminal repeats and it will replace the *rep* and *cap* sequences. The final AAVV will enter the cell nucleus and persist in different states. The first one involves the conversion of the AAVV genome into double-stranded circular episome which will later become a concatamer and provide a long-term transgene expression, particularly in non-dividing cells. The second option, presented in 0.1% of AAVV, is the integration at non-homologous sites of the host genome as single-copy proviruses or concatamers. In both options, there will be the presence of transgene expression.[A31477]