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Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a seldom encountered disorder characterized by maternal inheritance and features of mitochondrial disease. It results in bilateral vision loss, mainly affecting the central retina due to damage to the retinal ganglion cells. At Protheragen, we provide a complete range of services pertaining to the diagnosis and therapeutic development of LHON.

Overview of Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited mitochondrial disorder that causes bilateral vision loss, primarily in young adults. Mutations in mitochondrial DNA (mtDNA) are responsible, mostly within the genes encoding complex I subunits of the electron transport chain (ETC) system. Cuts in oxidative phosphorylation decrease ATP production while reactive oxygen species (ROS) are overproduced, causing retinal ganglion cell (RGC) death alongside optic nerve atrophy. LHON is more common in males, with the condition surfacing in the second or third decade of life. Considerable research has been made into the condition, but as of now, there is no concrete cure available; therapeutics remain mainly supportive.

Elucidation of epigenetic involvement in the progression of mitochondrial diseases.

Fig. 1 Illustration of how epigenetics involved in mitochondrial disease progression. (Devi S. M., et al., 2021)

Diagnostics Development for Leber Hereditary Optic Neuropathy (LHON)

Genetic Testing
The mtDNA mutations associated with Leber Hereditary Optic Neuropathy (LHON) can be elucidated through the technique of genetic testing, which happens to be one of its cornerstones. Genetic alterations in the mitochondrial genome can also be identified utilizing Sanger sequencing or next-generation sequencing (NGS). LHON is most exacerbated with the prognosis lacking, with the most common identified mutation G11778A associated with the ND4 subunit of complex I. Along with confirming the diagnosis, genetic testing significantly aids in genetic counseling and associated risk evaluation.

Imaging Techniques
Optical coherence tomography (OCT) is capable of measuring the retinal nerve fiber layer (RNFL) thickness non-invasively. In the acute stage of LHON, RNFL swelling is noted due to axonal swelling, and subsequent thinning is noted in the chronic stage. OCT measures the quantitative changes of RNFL, thus aiding in diagnosis and monitoring the disease progression. Furthermore, fundus photography and fluorescein angiography can demonstrate peculiar changes related to the fundus, like optic disc hyperemia and peripapillary telangiectasia, that are typical in the acute stage of LHON.

Therapeutics Development for Leber Hereditary Optic Neuropathy (LHON)

Antioxidant Therapies

Antioxidant therapies are aimed at controlling the amount of oxidative stress inflicted by the overproduction of ROS in the body with regards to LHON. Coenzyme Q10 and its derivative idebenone have been evaluated widely for their ability in aiding mitochondrial processes and guarding against injury to the Retinal Ganglion Cells (RGCs).

Gene Therapy

Therapeutic gene manipulation aims at the direct genetic basis of the condition, making it a key therapeutic option for LHON. It consists of supplying a functioning version of the gene in question (for instance ND4) via RGCs with viral vectors like adeno associated virus (AAV).

Pharmacologic Activators of Mitochondrial Biogenesis

The purpose of pharmacologic activators of mitochondrial biogenesis is to enhance the mass and function of mitochondria, with the possibility of offering some protection from the dysfunction of mitochondria. Fibrate compounds, metformin, and AICAR have been studied for their ability to stimulate PPAR (Peroxisome Proliferator-Activated Receptors) and AMPK (Adenosine Monophosphate-Activated Protein Kinase) which subsequently leads to mitochondrial biogenesis. Research on animals suggests that these compounds can postpone the expression of symptoms associated with mitochondrial myopathies and increase life expectancy.

Our Services

Protheragen offers a comprehensive suite of services to support the development of diagnostics and therapeutics for LHON. These services span the entire preclinical research process, from initial target identification and validation to in vivo efficacy studies. Protheragen leverages cutting-edge technologies and scientific expertise to accelerate the development of novel therapeutics for this debilitating condition.

Diagnostics Development

Therapeutic Development

Disease Models

Rotenone-Induced Models
Ndufs4 Double-knockout Models
mtDNA Mutation Models
Intraocular Injection of Viral Vectors Carrying Human Pathologic Complex I Subunits (e.g., ND4)

Protheragen understands that each research program is unique. Therefore, we offer customized services to meet the specific needs of our clients. If you are interested in our services, please feel free to contact us.

References

Devi, S. Mohana, et al. "Mitochondrial function and epigenetic outlook in Leber's Hereditary Optic Neuropathy (LHON)." Neurology Perspectives 1.4 (2021): 220-232.
Hage, Rabih, and Catherine Vignal-Clermont. "Leber hereditary optic neuropathy: review of treatment and management." Frontiers in Neurology 12 (2021): 651639.