TY - JOUR

T1 - Leber hereditary optic neuropathy

T2 - new and emerging therapies

AU - Davila-Siliezar, Pamela

AU - Carter, Michael

AU - Milea, Dan

AU - Lee, Andrew G.

PY - 2022

Y1 - 2022

N2 - Purpose of review To review recent therapeutic advances in Leber hereditary optic neuropathy (LHON). Recent findings Idebenone, a synthetic analog of ubiquinone (Coenzyme Q10) is an antioxidant and component of the mitochondrial electron transport chain. Since the initial approval of the drug in 2015 in Europe, recent trials have evaluated its role as prolonged treatment in LHON. Gene therapy has recently emerged as a promising alternative for the treatment of LHON. Among several investigations, RESCUE and REVERSE are two phase 3 clinical trials of gene therapy in patients with LHON in early stages. Results in these trials have shown a bilateral visual acuity improvement with unilateral intravitreal injections at 96 weeks and sustained visual improvement after 3 years of treatment. The most recent REFLECT phase 3 clinical trial in LHON has shown significant improvement of vision after bilateral intravitreal injections compared with the group that received unilateral injections. Historically, LHON has been considered an untreatable disease, but recent developments show that new pharmacological and gene therapy approaches may lead to visual recovery. Further studies are needed to support these data.

AB - Purpose of review To review recent therapeutic advances in Leber hereditary optic neuropathy (LHON). Recent findings Idebenone, a synthetic analog of ubiquinone (Coenzyme Q10) is an antioxidant and component of the mitochondrial electron transport chain. Since the initial approval of the drug in 2015 in Europe, recent trials have evaluated its role as prolonged treatment in LHON. Gene therapy has recently emerged as a promising alternative for the treatment of LHON. Among several investigations, RESCUE and REVERSE are two phase 3 clinical trials of gene therapy in patients with LHON in early stages. Results in these trials have shown a bilateral visual acuity improvement with unilateral intravitreal injections at 96 weeks and sustained visual improvement after 3 years of treatment. The most recent REFLECT phase 3 clinical trial in LHON has shown significant improvement of vision after bilateral intravitreal injections compared with the group that received unilateral injections. Historically, LHON has been considered an untreatable disease, but recent developments show that new pharmacological and gene therapy approaches may lead to visual recovery. Further studies are needed to support these data.

KW - gene therapy

KW - idebenone

KW - Leber hereditary optic neuropathy

KW - mitochondrial diseases

KW - optic neuropathy

KW - GENE-THERAPY

KW - DNA

KW - IDEBENONE

KW - TRIAL

U2 - 10.1097/ICU.0000000000000891

DO - 10.1097/ICU.0000000000000891

M3 - Review

C2 - 36066375

VL - 33

SP - 574

EP - 578

JO - Current Opinion in Ophthalmology

JF - Current Opinion in Ophthalmology

SN - 1040-8738

IS - 6

ER -