Therapy Shows Improved Vision in Rare Mitochondrial Disease, Follow-up Results Show

Therapy Shows Improved Vision in Rare Mitochondrial Disease, Follow-up Results Show


Patients with Leber’s hereditary optic neuropathy (LHON), a rare genetic mitochondrial disease that leads to vision loss, show sustained improvement in a follow-up to a Phase 1/2 clinical trial with GenSight Biologics’ therapy candidate GS010.

Patients recruited to the study had been diagnosed with LHON for approximately six years. After 78 weeks of follow-up, promising results were reported, with improved vision in the eye that was treated.

LHON is inherited through the maternal mitochondrial genes. It causes degeneration of retinal ganglion cells, a specific type of neurons in the retina. This condition begins with blurring and clouding, generally in a person’s teens or 20s.

In this study (NCT02064569), patients were administered a single intravitreal injection of Gs010 in the eye mostly affected by the disease, while the better-seeing eye was left untreated.

Visual acuity in patients was checked using the LogMAR eye chart that comprises rows of letters and uses a logarithmic scale. According to this scale, “0” indicates no vision loss and higher values indicate poorer vision.

When patients started the treatment, the worse-seeing eyes had a median visual acuity of 2.79 LogMAR (approximately equivalent to a hand motion at 1 meter) and untreated better-seeing eyes had a median acuity of 2.01 LogMAR (approximately equivalent to counting fingers at 50 cm).

At 1.5 years after treatment, the treated eyes show increased vision equivalent to a mean decrease of 0.61 in the LogMAR and a mean improvement of +30 ETDRS letters, another scale used for visual acuity.

For untreated eyes, there was a 0.31 decrease in LogMAR, equivalent to a mean improvement of +15 ETDRS letters. The results of GS010 treatment show a higher benefit of treated worse-seeing eyes compared to untreated better-seeing eyes.

Patients who had vision loss for two years or less at the time of injection demonstrated an earlier treatment effect in favor of the treated eye.

“The confirmatory trends of week 48 data after 1.5 years of follow-up confirm significant hope for patients suffering from LHON. The insights gained from this and forthcoming data will be tremendously helpful as GenSight works to develop a therapy for this very severe disease with no existing curative treatment,” Catherine Vignal, an ophthalmologist on the team, said in a press release.

The results confirm the safety and tolerability of GS010, which is based on the specific delivery of a functional gene to the mitochondria, restoring its proper function.

While the follow-up study is still ongoing, GenSight Biologics is currently recruiting patients for two Phase 3 clinical studies, RESCUE (NCT02652767) and REVERSE (NCT02652780) in Europe and the United States, to assess the effectiveness of GS010 in patients with vision loss up to one year at the time of treatment.

According to the news release, GS010 leverages a mitochondrial targeting sequence proprietary technology platform which, when associated with the gene of interest, allows the platform to address mitochondria defects using an AAV (adeno-associated virus) vector.

“The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function,” the release states.

“We are very encouraged by the latest results indicating a sustainable clinical benefit for patients in this long-term follow up,” said Bernard Gilly, co-founder and CEO of GenSight.

“This data continues to support the design of our two Phase III studies with GS010 for the treatment of Leber’s hereditary optic neuropathy, which are currently ongoing in the U.S. and Europe, addressing patients with an early onset of vision loss,” he said.

Gilly thanked the trials’ participants and their families, “which ultimately will help us find a cure for this devastating condition.”


  1. Abdul Azeez says:

    Dear Teresa,
    I read your artice. It’s influnced me a lot. My son 17 years old boy has epilepsy sine 9 years old. It is not frequently happening. so far only 8 episodes happened. Doctors says there is some patches in brain lob, it could be demyelination or dysmylination. So many test has done all the test are negative, so they could not come in to a final conclution. some doctors says it may be due to some mitocontrial disorders. I have send a blood sample for VLCFA test (very long chain fatticy acid) to US and result is awaited. He is clinically perfect and currently under suppressive medicines. I am planning to have stemcell theraphy in Germany. Could you please advice me in this regards.Your openion will be highly appreciated.

    Thanks and regards

    Abdul Azeez

  2. GIorgio Terziani says:

    mitochondrial damage
    Cellfood™ improves respiratory metabolism of endothelial cells and inhibits hypoxia-induced reactive oxygen species (ros) generation.
    Ferrero E1, Fulgenzi A, Belloni D, Foglieni C, Ferrero ME.
    Author information
    Endothelial mitochondria, the major site of ATP generation, modulate the intracellular dynamics of reactive oxygen species (ROS), which, in turn, control endothelial function. Adequate oxygen (O(2)) supply is required by endothelial cells (EC). Both hypoxia and hyperoxia may favor the overproduction of ROS leading to oxidative stress, mitochondrial damage and endothelial dysfunction. We investigated the capability and mechanisms of Cellfood™ (CF), an antioxidant compound, to modulate O(2) availability and mitochondrial respiratory metabolism and to regulate ROS generated by hypoxia in EC in vitro. Human umbilical vein endothelial cells (HUVEC) and ECV-304 were evaluated for the O(2) consumption using a Clark’s electrode. The O(2) consumption rate rose, during the first minutes after CF addition and was associated with increase in mitochondrial oxidative capacity and good cell viability. Similar behaviours were observed when EC were exposed to CF for up to 8 days. The O(2) consumption increased and was accompanied by both intracellular rise of ATP and maintainment of LDH concentration. Hypoxia-induced ROS generation was significantly inhibited by CF, through the up-regulated expression of MnSOD, an anti-oxidant responsible for mitochondrial function preservation. The EC hypoxic response is mediated by the hypoxia master regulator HIF-1alpha whose activation was attenuated by CF, in concomitance with MnSOD up-regulation. Our results suggest a role for CF in improoving respiratory metabolism and in activating anti-oxidant mechanisms in EC, thus preserving endothelial function.

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