Leber inherited optic neuropathy (LHON) is a maternally inherited progressive bilateral optic atrophy often seen in young men from adolescence to middle age. At Protheragen, we commit to supporting our clients with a range of support and services directed specifically at ensuring success with LHON therapeutic development.
Introduction to LHON
LHON is the most common primary mtDNA disorder, and most individuals are identified to carry one of the three most common mtDNA point mutations, m.3460G>A (MTND1), m.11778G>A (MTND4), and m.14484T>C (MTND6). These mutations alter the activity of mitochondrial complex I, which hampers ATP synthesis, increases oxidative stress, and culminates in apoptosis of optic nerve cells. Individuals with LHON present bilateral subacute vision loss because of selective degeneration of retinal ganglion cells (RGCs) in the inner retina leading to 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 its active development phase. Recent research focuses on understanding more profoundly the pathogenesis of LHON and formulating new therapeutic methods. As for the mechanisms of the disease, researchers have studied the retinal nerve fiber layer thickness, and the dynamic changes in the optic nerve head region of the LHON individuals for early diagnostics clues, and have come up with something new. Moreover, some studies have revealed more extra-ocular manifestations of LHON, such as arrhythmias, and these developments pave the way for a better understanding of the 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
It is possible to determine the mutation type of mitochondrial DNA associated with LHON while ruling out other mitochondrial diseases through targeting detection of mitochondrial DNA, polygenic testing, and complete mtDNA sequencing.
Auxiliary Detection
Measurement of the retinal nerve fiber layer thickness and the assessment in the area of the optic nerve head dynamics are considered early diagnostic measures that improve the accuracy of LHON diagnosis and the promptness of therapy.
Novel Therapies of LHON
Novel therapeutic approaches for Leber inherited optic neuropathy encompass the following.
Therapy With CoQ10 Analogues and Idebenone
Such medications as CoQ10 analogs and idebenone may relieve symptoms in some LHON individuals and aid visual recovery in some individuals. This therapy aims to improve mitochondrial function, reduce oxidative damage, and protect nerve cells by administering CoQ10 analog and idebenone.
Gene Therapy
Recombinant adeno-associated virus vectors (rAAV) have been employed to complement existing defects within the mitochondrial respiratory chain by delivering the unmutated MT-ND4 gene. Reported that certain individuals exhibit significant improvements in vision owing to rAAV carrier therapy.
Fig.2 Gene therapy as part of a treatment guide for LHON. (Hage, R., et al., 2021)
Our Services
Protheragen is a preclinical research service provider that specializes in mitochondrial diseases which implies it proffers technological and services support to researchers and biotechnology companies. Our offerings encompass but are not limited to the following.
Model Development Service
Utilizes state-of-the-art equipment and considerable experience to aid clients in developing animal models of Leber Hereditary Optic Neuropathy and performing detailed behavioral, imaging, and molecular biology analyses.
Drug Screening Service
The use of high-throughput screening methods and advanced cellular models helps to evaluate potential drug candidates for Leber hereditary optic neuropathy, thus saving time in the new drug development processes.
Toxicology Service
A group of specialists in the toxicology of our company will conduct an integrated assessment of the tolerability and safety of candidate drugs to guarantee the smooth running of subsequent studies.
Gene Therapy Development Service
Targeting gene therapy of LHON is an emerging primary focus, our work is underway to develop gene therapy strategies capable of fixing LHON-causing genetic defects and restoring mitochondrial activity.
Our Advantages
Protheragen's mission entails offering exceptional support and resources to researchers engaging in research focused on LHON, thereby promoting better and faster progress in the area of mitochondria 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
