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Watch phase I/II LHON patient testimonial

This video is extracted from a shooting produced by Le Monde Pharmaceutique

LHON is a rare maternally inherited mitochondrial genetic disease that causes irreversible and severe loss of sight leading to blindness and disability in teens and young adults.

The dramatic loss of vision experienced by LHON patients is life changing. It causes disability and affects patients and their families socially, emotionally, and financially. LHON greatly alters a patient’s ability to perform activities of daily living and reduces a patient's autonomy. The vision-related quality of life of patients with LHON is poor, and their quality of life in general can be affected without proper support from the family and caregivers.

LHON is caused by defects in mitochondrial genes encoding for proteins called NADH dehydrogenase. 95% of LHON cases are due to mutations in ND1, ND4 and ND6 mitochondrial genes that encode proteins of the respiratory chain Complex I, an important component of energy production within the mitochondrion and therefore the cell. The ND4 mutation is responsible for the majority of cases (representing around 70% in Europe and North America and 80 to 85% in Asian countries).

Although the genetic defect is present throughout the body, LHON symptoms are almost uniquely limited to retinal ganglion cells, or RGCs, dysfunction and optic nerve atrophy. RGCs are located near the inner surface of the retina. They receive visual information from photoreceptors. RGCs collectively transmit image-forming and non-image forming visual information from the retina to several regions in the brain. Once the RGCs degenerate, signals can no longer be transmitted to the brain and the patient turns blind.

Onset of vision loss due to LHON typically occurs between 15 and 35 years of age. Vision loss often occurs in a bilateral sequential fashion, the second eye being affected after the first one with a median delay of two months.

View the 2015 ARVO poster on the experiences and hopes of LHON patients and caregivers:

GenSight LHON ARVO Poster 2015


GS010 is an AAV2 containing the human wild-type ND4 gene, which is being developed for the treatment of Leber Hereditary Optic Neuropathy (LHON) associated with mutation in the ND4 gene.

GS010 allows an efficient expression of the ND4 gene, encoding for a protein which is normally produced into the mitochondria. For such a purpose, ND4 is flanked by a Mitochondrial Targeting Sequence, allowing addressing of mRNA to the outer mitochondrial membrane. This results in synthesis of ND4 protein within the mitochondrial membrane that is shuttled and integrates Complex I of the respiratory chain in order to obtain an efficient rescue of the defect.

We believe that GS010 will deliver the first treatment for LHON, thereby addressing a significant unmet medical need for this rare disease. Phase I/II trial for GS010 has been completed in France. We are now conducting two Phase 3 trials, RESCUE & REVERSE, in Europe and in US to evaluate the efficacy of GS010 on LHON patients with on early onset of disease of less than one year. Both recruitment is completed, hence topline data are expected by Q2 and Q3 2018 for REVERSE and RESCUE respectively.

Meanwhile two clinical trials are being initiated: REFLECT study to evaluate the efficacy and safety of bilateral intravitreal injection of GS010 for the treatment of vision loss up to 1 year and REALITY LHON Registry study to understand the evolution of visual functional and structural changes and other associated symptoms in patients with LHON.


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