Summary: A breakthrough gene therapy that has been shown to be effective in treating an inherited blinding eye disease in dogs is now ready for clinical trials in humans with the rare disease retinitis pigmentosa.
The therapy, which halts vision loss by introducing a normal copy of the CNGB1 gene, could potentially benefit around 2 million affected people worldwide.
Highlights:
- The gene therapy has been successfully tested in dogs with an inherited eye disease and is now ready for clinical use in human patients with retinitis pigmentosa.
- Retinitis pigmentosa affects approximately 2 million people worldwide, including 100,000 cases in the United States alone.
- The therapy works by introducing a normal copy of the CNGB1 gene, rescuing normal rod cell function, preserving cone function, and preserving retinal structure by arresting photoreceptor degeneration.
Source: University of Michigan
A successful gene therapy tested at Michigan State University in dogs with an inherited eye disease is ready to be developed for clinical use in human patients with a rare disease called retinitis pigmentosa.
Simon Petersen-Jones, Professor and Donald R. Meyers and William E. Dunlap Chair in Canine Health at the Michigan State College of Veterinary Medicine, and collaborators have published “Development of a translatable gene augmentation therapy for CNGB1-Retinitis Pigmentosa” in the high-impact journal Molecular therapy.
Retinitis pigmentosa encompasses a group of rare genetic diseases that cause vision loss due to the death of light-sensitive cells in the retina. Vision loss begins at a young age and progresses throughout life.
“There is currently an unmet need for treatment to save the vision of patients with CNGB1-retinitis pigmentosa,” Petersen-Jones said. “This promising therapy that works so well in dogs is now sufficiently developed that the next step is to take it forward for a clinical trial in human patients.”
The Cleveland Clinic estimates that retinitis pigmentosa affects approximately 2 million people worldwide, including 100,000 in the United States. And currently there is no cure, but this therapy may be able to stop vision loss in patients with this specific form of retinitis pigmentosa.
About Research
Humans and dogs share a gene – the beta 1 cyclic nucleotide channel (CNGB1)— which, when mutated, causes eye disease. Dogs develop a form of progressive retinal atrophy, while humans develop a form of retinitis pigmentosa.
Since gene therapy works in dogs with progressive retinal atrophy due to CNGB1 genetic mutations, and because humans develop retinitis pigmentosa (the human equivalent of progressive retinal atrophy in dogs) due to CNGB1 genetic mutations, the therapy is now ready to be developed to help people with CNGB1-retinitis pigmentosa.
“We very much hope that this therapy will show the same positive results seen in dogs in a human clinical trial and lead to an FDA-approved therapy for CNGB1-retinitis pigmentosa,” says Petersen-Jones.
In the study, Petersen-Jones used an adeno-associated virus, or AAV, vector to deliver a normal copy of the CNGB1 gene under the control of a new gene promoter.
The new promoter, which was developed by the Petersen-Jones collaborators, is a modified form of the human rhodopsin promoter, an important gene in retinal rods. The new promoter guarantees that the CNGB1 introduced by therapy is active only in the target cell – the rod photoreceptor.
AAV is a conditioned serotype 5 with the short rhodopsin promoter, CNGB1 combination of genes (AAV5-RHO-CNGB1). The therapy is injected under the retina so that it is introduced into the target light-sensitive rod cells, which require CNGB1 operate and survive.
The therapy:
- Rescues normal function in rod cells and restores rod-mediated vision by introducing a normal working copy of CNGB1
- Stops the accumulation of toxic amounts of cyclic guanosine monophosphate in normally functioning rods, which, if not slowed down, causes cell death
- Preserves cone function, which in untreated eyes is lost when rod cells die
- Preserves retinal structure by stopping photoreceptor degeneration
Funding: This study involved 20 authors from 8 international institutions, including universities and industry. Their findings establish the long-term effectiveness of gene therapy and are the result of previous research funded by the National Institutes of Health.
About this news about gene therapy and vision research
Author: Neighborhood Kim
Source: University of Michigan
Contact: Ward Kim – Michigan State University
Picture: Image is credited to Neuroscience News via DALL-E 2
Original research: Free access.
“Development of a translatable gene augmentation therapy for CNGB1-Retinitis pigmentosa” by Simon Petersen-Jones et al. Molecular therapy