Solutions to a Radical Problem: Overview of Current and Future Treatment Strategies in Leber’s Hereditary Opic Neuropathy
Leber’s Hereditary Optic Neuropathy (LHON) is the most common primary mitochondrial DNA disorder. It is characterized by bilateral severe central subacute vision loss due to specific loss of Retinal Ganglion Cells and their axons. Historically, treatment options have been quite limited, but ongoing clinical trials show promise, with significant advances being made in the testing of free radical scavengers and gene therapy. In this review, we summarize management strategies and rational of…
Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy
CONCLUSIONS: Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.
Optic nerve lesion length is a biomarker of visual disability in the pre-chronic phase of Leber’s hereditary optic neuropathy
CONCLUSION: ON length with T2-STIR hyperintensities was positively associated with both BCVA and MD, and it was suspected to be a biomarker of visual disability in the pre-chronic phase of LHON.
Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation
CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection.
Analysis of Human Clinical Mutations of Mitochondrial ND1 in a Bacterial Model System for Complex I
The most common causes of mitochondrial dysfunction and disease include mutations in subunits and assembly factors of Complex I. Numerous mutations in the mitochondrial gene ND1 have been identified in humans. Currently, a bacterial model system provides the only method for rapid construction and analysis of mutations in homologs of human ND1. In this report, we have identified nine mutations in human ND1 that are reported to be pathogenic and are located at subunit interfaces. Our hypothesis…
Developments in the Treatment of Leber Hereditary Optic Neuropathy
PURPOSEOF REVIEW: To outline the current landscape of treatments for Leber hereditary optic neuropathy (LHON) along the therapeutic delivery pipeline, exploring the mechanisms of action and evidence for these therapeutic approaches.
Leber’s hereditary optic neuropathy companied with multiple-related diseases
CONCLUSION: Leber’s hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile.
Clinical application of multicolor imaging in Leber hereditary optic neuropathy
CONCLUSION: As an adjunct to SD-OCT, the MC image, particularly the GR and BG can delineate RNFL more effectively than CFP. The MC image may be a useful adjunct to OCT for detecting or monitoring never fiber bundle defects, providing inexpensive and rapid methods that can quickly identify patients with high suspicion of LHON.
Case report: Long-term follow-up of two patients with LHON caused by DNAJC30:c.152G>A pathogenic variant-case series
CONCLUSIONS: Presented are two autosomal recessive LHON (arLHON, OMIM:619382) cases with the same DNAJC30:c.152G>A pathogenic variant and different degrees of spontaneous visual recovery despite progressive RNFL thinning during a long-term follow-up. This mutation should be screened in every atypical LHON patient.
Medical treatments in Leber’s hereditary optic neuropathy
Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disease caused by a mutation of mitochondrial DNA. LHON targets retinal ganglion cells (RGC), whose axons form the optic nerve. The mutation that leads to LHON is silent until an unknown trigger causes dysfunction of complex I in the mitochondria of RGC. This results in discontinuation of RGC energy production and, eventually, RGC apoptosis. Patients experience bilateral sequential central scotoma over the course of a few…