Leber hereditary optic neuropathy (LHON) is a rare genetic disorder affecting the optic nerve, primarily causing vision loss in young adults, with an incidence of about one in 50,000 people.

Lenadogene nolparvovec, an adeno-associated virus (AAV)-based gene therapy, aims to correct the genetic defect responsible for LHON and has shown early efficacy in previous clinical studies.

The long-term RESTORE study, published in JAMA Ophthalmology, provides a follow-up on the Phase III trials RESCUE and REVERSE, focusing on the therapy's lasting effects.

The study monitored 55 patients over five years, revealing a mean best-corrected visual acuity (BCVA) improvement from 1.5 logMAR (20/600) at baseline to 1.4 logMAR (20/500) at year five.

Future research should explore the therapy's effects on younger populations and further investigate the observed contralateral effects.

Approximately 66.1% of patients achieved at least a -0.3 logMAR improvement in one eye, indicating significant and lasting benefits from the therapy.

While no significant differences were observed between treated and sham eyes, this may support the hypothesis of a bilateral therapeutic effect from vector DNA transfer.

Mild ocular adverse events were reported in 38.7% of patients, including cataracts and intraocular inflammation, with the latter decreasing significantly over the follow-up period.

Intraocular inflammation was noted in four patients during the follow-up, but no permanent complications were attributed to the therapy.

The projected cost of lenadogene nolparvovec is $725,000 per patient, raising concerns about the financial burden on healthcare systems and patients.

Due to the complexities of previous trial results, additional studies will likely be needed for regulatory approval in the U.S. and Europe, with expectations for FDA approval in the next three to four years.

Co-author José-Alain Sahel emphasized that despite the positive outcomes, obtaining FDA approval for the treatment will require several years.