An investigational gene therapy, GS010, is showing some promise in helping people who recently began to lose their vision due to Leber’s hereditary optic neuropathy (LHON), according to data from an ongoing clinical trial.
A presentation of the data, “Intravitreal rAAV2/2-ND4 (GS010): A gene therapy for vision loss in Leber’s Hereditary Optic Neuropathy (LHON) caused by the G11778A ND4 mitochondrial mutation,” is set for April 25 at the 2017 annual meeting of the American Association of Neurology (AAN), taking place through April 28 in Boston. It will be given by José-Alain Sahel, MD, co-founder of GenSight Biologics, the developer of GS010.
The Paris-based company’s lead product candidate, GS010, was designed to be the first gene replacement therapy targeting LHON, a rare inherited mitochondrial disease caused by ND4 mitochondrial gene mutation. Mainly affecting adolescents and young adults, LHON is characterized by irreversible vision loss due to a degeneration of retinal ganglion cells. In more severe cases, this disease can lead to blindness.
A Phase 1/2 clinical trial (NCT02064569) is evaluating the safety and tolerability profile of GS010 in 15 LHON patients who are being given the treatment as a single intravitreal injection, or an injection directly into the eye.
According to 48-week data being presented at AAN, patients with recent onset of vision loss showed an improvement in the treated eye compared to the study’s start (and compared to sight in the untreated eye). However, this beneficial effect was not seen in chronically and more severely affected patients.
The treatment was well-tolerated by most of the patients, with no major adverse side effects reported. The most common side effects were mild and treatable cases of ocular inflammation and intraocular pressure.
Two Phase 3 trials, in Europe and the U.S., are also evaluating the effectiveness of GS010 in early-onset LHON patients with the ND4 mutation: The RESCUE (NCT02652767) study for patients with vision loss of six months or less, and the REVERSE (NCT02652780) study is assessing patients whose vision loss began more than six months but less than a year ago.
On its website, GenSight states that its Mitochondrial Targeting Sequence (MTS) platform allows for delivery of the correct form of the gene responsible for the disease inside the cells. This allows the production of the correct protein that was lacking in the mitochondria, and can overcome the effects of the damaged gene.