Opus Genetics – the next BEST thing!
Opus Genetics has reached an important milestone in Best disease research, dosing the first patients in its phase 1/2 trial of OPGx-BEST1.
Opus Genetics have announced this week that they have dosed the first patients in their phase 1/2 clinical trial for OPGx-BEST1, a treatment in development for Best disease.
“The successful dosing of the first patient underscores both the potential promise of gene therapy in ophthalmology and the dedication of the entire community working to make these treatments a reality. It’s inspiring to see years of scientific progress translate into potentially meaningful advances for patients and families.” – Dr. Charles Wykoff, Surgical Retina Specialist and Ophthalmologist at the Retina Consultants of Texas.
What is Best Disease?
Best disease, otherwise known as Best Vitelliform Macular Dystrophy (BVMD) is an inherited retinal condition that causes progressive degeneration of the macula, the central part of the retina which we use for seeing fine detail in high definition. Best disease is one of the most common inherited forms of macular degeneration, affecting approximately 1 in 10,000 people.
It is caused by variations in the BEST1 gene. This gene carries the information needed to produce the protein bestrophin-1, which can be found in the retinal pigment epithelium (RPE), a layer of cells that support the light sensing photoreceptors in the retina.
The Bestrophin-1 protein mainly helps with regulating ion flow across the RPE cell membrane, maintaining normal fluid balance between the RPE and the retina, and supporting the health and function of photoreceptors by keeping the environment around them stable. When there are mutations in the BEST1 gene, this causes the Bestrophin-1 protein to malfunction or to be made incorrectly. To see why this happens, please watch this short animation on Why Genes Matter https://youtu.be/q0seHoTxyt4
This means that the RPE struggles to remove the toxic waste byproducts of the normal visual cycle from under the retina, leading to the accumulation of toxins. This is what gives the characteristic yellow ‘egg-yolk’ appearance found in Best disease. This accumulation of toxins then damages the photoreceptors over time, leading to progressive vision loss.
What is OPGx-BEST1?
OPGx-BEST1 is an adeno-associated viral vector (AAV) gene therapy. This means that a small virus, that doesn’t cause illness in humans, is used as a delivery system to introduce or alter genetic material within cells. OPGx-BEST1 is administered via a subretinal injection.
How does it work?
The gene therapy will deliver a healthy copy of the BEST1 Gene into the RPE, allowing for production of the bestrophin-1 protein. This approach aims to retore normal function of the RPE cells so that they can provide proper support to photoreceptors as intended.
The trial:
This phase 1/2 trial aims to evaluate the efficacy, safety and tolerability of a single sub-retinal injection of OPGx-BEST1 into one eye of an adult with Best disease. This trial will also explore the most appropriate dose strength for clinical development. A minimum of 5 people will be involved in the testing of each of the two doses. The long-term follow-up of this trial, including 17 visits in total over the course of 5 years will evaluate the immunogenic effects of administration.
Opus Genetics currently have only one trial site for OPGx-BEST1 located in the US, and aim to obtain preliminary data from a Phase 1/2 study by the first quarter of 2026.
To read more about Opus Genetics or OPGx-BEST1 please visit Opus Genetics – Home.
To read more about the trial itself, please visit Study Details | NCT07185256 | Safety and Tolerability of Subretinally Injected OPGx-BEST1 in Patients With Best Vitelliform Macular Dystrophy (BVMD) or Autosomal-Recessive Bestrophinopathy (ARB) | ClinicalTrials.gov.