Mito research around the world

GS010 Gene Therapy

What is GS010 gene therapy?

A French biotechnology company Gensight Biologics is working on a gene therapy-based approach for treatment of a particular form of mitochondrial disease known as Leber’s hereditary optic neuropathy (LHON). LHON is caused by genetic mistakes (mutations) in mitochondrial DNA and symptoms are almost uniquely limited to the cells at the back of the eye. LHON is characterised by a rapid loss of sight in both eyes, which usually happens between 15 and 35 years of age.

How does gene therapy work?

Gene therapy is the introduction of normal genes into cells to replace missing or defective ones in order to correct the genetic disorder. To do this, the normal gene is packaged into a viral transporter called a vector and injected into the part of the body where it is needed. The use of viral vectors has been shown to be a safe way of transferring genes into cells.

What is GS010 supposed to do?

The most common genetic mutation that causes LHON is in a gene called ND4 found within the mitochondrial DNA. The ND4 gene usually produces a building block that forms part of the energy chain and is therefore important for energy production by the mitochondria. If there is a mutation in ND4 associated with LHON, this can lead to decreased energy production and higher levels of harmful chemicals called ‘free radicals’ within certain cells of the eye. This, in turn, can lead to extensive cell damage and loss of vision.

GS010 is a viral vector that contains the normal ND4 gene. By injecting GS010 into the cells at the back of the eye, the defective building block within the energy chain can be replaced with a normal version. This may restore the ability of the cells to produce energy and could lead to improvements in vision.

Is it a cure?

GS010 aims to correct the underlying genetic mutation that causes LHON within certain cells of the eye. It may be possible to administer the treatment once, or a limited number of times, to achieve a long-term benefit and potentially a cure for vision loss. The genetic mutation will still be present throughout other cells of the body but the symptoms of LHON are often restricted to the eyes only.

What types of mitochondrial disease could it treat?

Gensight plan to investigate gene therapy to treat other LHON mutations. They have already initiated a research program for their next potential product candidate, GS011, which targets the ND1 gene mutation causing LHON.

In theory, gene therapy could be used to treat other mitochondrial diseases caused by different genetic mutations. The difficulty is delivering enough of the normal gene to the part of the body where it is needed. This is especially challenging for mitochondrial diseases that can affect multiple tissues and organs.

Have there been any trials?

Gensight published results from a phase 1/2 study in June 2016. This confirmed good safety and tolerability of GS010 and improved vision in patients with a disease onset of less than 2 years. Further results were published in June 2017 that confirmed the long-term safety of GS010 after nearly 2 years follow-up. The improved vision in LHON patients with less than 2 years visual loss before treatment also continued over this time period.

Two parallel phase 3 clinical trials, known as the RESCUE and REVERSE studies, are currently ongoing in several medical centres within the US and Europe, including a centre in the UK. Both studies aim to assess the benefits of GS010 for treatment of vision loss in LHON patients with the ND4 mutation, either with a disease onset of up to 6 months (RESCUE) or up to 1 year (REVERSE). Both trials involve participants having a single eye injected with GS010 whilst the other eye receives a sham injection.

What is the latest update on this trial?

Results from the ongoing REVERSE study showed that GS010 improves vision and quality of life in patients with LHON. This improvement was reported at both week 48 and 72 of the trial using a questionnaire that was completed by all participants to assess the impact of vision loss on their daily life. The questionnaire will be repeated at 96 weeks to ensure the benefits of GS010 can be maintained over time.

The latest results from the ongoing RESCUE study showed that in both GS010 and sham-treated eyes, patients’ vision initially deteriorated between weeks 24 and 48 of the trial before beginning to recover from week 48 to week 96. At week 96, eyes treated with GS010 had recovered more than two-thirds of their initial vision loss, with similar improvements reported in eyes receiving the sham injection. According to Gensight, these improvements exceed those seen in untreated LHON patients who participated in a natural history study. However, it is unclear at this stage why visual recovery is reported in both eyes.

What next?

Another phase 3 trial, known as the REFLECT study, completed enrolment in July 2019, with nearly 100 patients recruited from across a number of countries including the UK. This study will evaluate the efficacy and safety of a single GS010 injection into both eyes for the treatment of vision loss for up to 1 year from disease onset in LHON.

Is there more information?

More information can be found using the following links:


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