The Leber inherited optic neuropathy (LHON) is a maternally transmitted mitochondrial disorder characterized by bilateral progressive vision loss in young males during adolescence to middle age. Protheragen is dedicated to providing our customers with comprehensive support and services to facilitate their success in the field of LHON.
Introduction to LHON
LHON is the most prevalent primary disorder of mitochondrial DNA (mtDNA), with the majority of patients carrying one of three main mtDNA point mutations, namely m.3460G>A (MTND1), m.11778G>A (MTND4), and m.14484T>C (MTND6). These mutations affect the function of mitochondrial complex I, leading to impaired energy production and increased oxidative stress, ultimately triggering apoptosis in optic nerve cells. LHON is characterized by bilateral subacute vision loss due to selective degeneration of retinal ganglion cells (RGCs) within the inner retina, resulting in optic nerve degeneration.
Fig.1 Pathophysiology of LHON. (Esmaeil, Ali., et al., 2023)
Research Progress of LHON
The study of Leber hereditary optic neuropathy is currently in an active stage of development. Recent research priorities encompass gaining a more profound comprehension of the pathogenesis of LHON and advancing novel therapeutic approaches. Concerning the pathogenesis, researchers have conducted comprehensive investigations on the retinal nerve fiber layer thickness and dynamic changes within the optic nerve head region in LHON patients to identify early diagnostic markers. Furthermore, certain studies have unveiled additional extra-ocular manifestations associated with LHON, such as arrhythmias, thereby providing further insights towards a comprehensive understanding of this disease.
Novel Diagnostic Methods of LHON
The diagnosis of Leber hereditary optic neuropathy involves the utilization of molecular genetic tests and auxiliary examinations.
Molecular Genetic Testing
By employing targeted detection of mitochondrial DNA, polygenic testing, and complete mtDNA sequencing, it becomes feasible to ascertain the mutation type associated with LHON while simultaneously excluding other mitochondrial disorders.
Auxiliary Detection
The measurement of retinal nerve fiber layer thickness and the assessment of optic nerve head area dynamics serve as early diagnostic indicators to facilitate more accurate LHON diagnosis and enable timely intervention in treatment.
Novel Therapies of LHON
Novel therapeutic approaches for Leber inherited optic neuropathy encompass the following.
Treatment With CoQ10 Analogues and Edetbenol
Medications such as CoQ10 analogs and edetbenol may potentially alleviate symptoms in patients with LHON and facilitate visual restoration in certain individuals. The purpose of this treatment is to enhance mitochondrial function, diminish oxidative stress, and safeguard nerve cells through the administration of CoQ10 analog and edetbenol.
Gene Therapy
Recombinant adeno-associated virus vectors (rAAV) are utilized to deliver the unmutated MT-ND4 gene, aiming to supplement defects in the mitochondrial respiratory chain. Clinical trials have demonstrated that rAAV carrier therapy exhibits significant improvements in vision for certain patients. These innovative therapies provide LHON patients with a more efficacious treatment option, thereby enhancing their quality of life.
Fig.2 Gene therapy as part of a treatment guide for LHON. (Hage, R., et al., 2021)
Our Services
As a preclinical contract research organization (CRO) specializing in mitochondrial diseases, Protheragen is dedicated to delivering comprehensive support and services to researchers and biotechnology firms. Our range of offerings encompasses but is not limited to the following.
Model Development Service
We possess extensive expertise and cutting-edge technology to assist clients in establishing animal models of Leber hereditary optic neuropathy, as well as conducting comprehensive behavioral, imaging, and molecular biology analyses.
Drug Screening Service
We can employ high-throughput screening technologies and advanced cell models to assist clients in assessing the efficacy of drug candidates for Leber hereditary optic neuropathy, thereby expediting the process of new drug development.
Toxicology Service
Our team of toxicology experts is capable of performing a comprehensive toxicological evaluation to assess the safety and tolerability of drug candidates, thereby ensuring the seamless execution of subsequent experiments.
Gene Therapy Development Service
We specialize in the development of gene therapy strategies focused on targeting LHON, to rectify underlying genetic abnormalities and reinstate mitochondrial functionality.
Our Advantages
The mission of Protheragen is to provide unparalleled support and services to researchers dedicated to LHON, facilitating the acceleration of innovation and progress in the field of mitochondrial diseases. If you are interested, please do not hesitate to contact us.
References
- Esmaeil, Ali.; et al. (2023). Leber's hereditary optic neuropathy: Update on current diagnosis and treatment. Frontiers in Ophthalmology, 2674-0826.
- Hage, R., & Vignal-Clermont, C. (2021). Leber Hereditary Optic Neuropathy: Review of Treatment and Management. Frontiers in neurology, 12, 651639. https://doi.org/10.3389/fneur.2021.651639
