--Must See--

Bioinformatics Summer Internship 2024 With Hands-On-Training + Project / Dissertation - 30 Days, 3 Months & 6 Months Duration

GenSight’s Gene Therapy for Genetic Vision Loss Successful in Follow-Up

GenSight Biologics has now published reports detailing the positive results of phase 1/2 clinical trial and long-term follow-up of GS010 in Leber Hereditary Optic Neuropathy (LHON) patients in Ophthalmology. The study demonstrated that GS010 (rAAV2/2-ND4) is safe and well tolerated 2 years after a single unilateral intravitreal administration.

It 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.

Caused by by defects in mitochondrial genes encoding for proteins called NADH dehydrogenase, 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.

GenSight Launch Clinical Trial of Gene Therapy in Retinitis Pigmentosa

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. 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.

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.

GS010 is an AAV2 that includes the ND4 gene, which is flanked by a Mitochondrial Targeting Sequence.

The study was an open-label single-center phase 1/2 clinical trial that included 4 dose-escalation cohorts and an extension cohort. Fifteen subjects with LHON carrying the ND4-G11778A mutation were prospectively enrolled. Each subject received a single intravitreal injection of rAAV2/2-ND4 in the worse-seeing eye.

The study design included an initial follow-up period of 48 weeks, followed by longer-term follow-up for an additional 4 years. The primary objective was the safety and tolerability of escalating doses of rAAV2/2-ND4. Secondary objectives included bio-dissemination and immunogenicity of rAAV2/2-ND4and evaluation of visual functions.

At week 96, there were no unexpected TEAEs, no serious adverse events related to the treatment or procedure, and no suspected unexpected serious adverse reactions. No deaths and no TEAEs leading to study discontinuation were reported. 94% of TEAEs were mild in intensity.

The most frequent ocular TEAEs were intraocular inflammation and IOP elevation. All ocular events resolved spontaneously or after appropriate therapy with IOP-lowering or anti-inflammatory therapy, except for 1 subject with ongoing mild vitritis, subsequently lost to follow-up but without documented worsening of vision. At week 96, no related TEAEs required ongoing treatment.

The biotech is currently conducting two phase 3 clinical studies (RESCUE and REVERSE) in Europe and the United States to assess the efficacy of GS010 in subjects affected with LHON due to the ND4 mutation, with vision loss up to 1 year at the time of treatment. Topline results at 48 weeks for REVERSE and RESCUE are expected in April 2018 and the third quarter of 2018, respectively.

This first-ever scientific publication of clinical data with GS010 is a major step forward for patients afflicted with LHON – a blinding disease affecting those in the prime of their life,” Dr. Catherine Vignal, investigator of the study and Chief of the Department of Ophthalmology at the Rothschild Foundation Hospital in Paris, siad in a company news release. “If these promising results are confirmed in the ongoing phase 3 studies, GS010 would offer a meaningful and life changing therapy for those so afflicted and become the standard of care for LHON.

In search of the perfect burger. Serial eater. In her spare time, practises her "Vader Voice". Passionate about dance. Real Weird.