Advances in Optogenetics
Various projects are in development to use Optogenetics to restore visual function. In this novel approach a light sensitive molecule is genetically delivered to the neural cells that will then transmit a message to the brain.
GenSight Biologics reported recently on a single patient in their Pioneer study, that was treated with their Optobionic GS030 system which genetically delivers a light sensitive molecule Opsin CrimsonR, derived from an algae to the retinal ganglion cells. These molecules react to amber light and are activated by a specialized pair of goggles transmitting pulses of amber light. The patient who has end stage Retinitis Pigmentosa [RP] was treated by Dr Jose-Alain Sahel, who reported that the patient was able to perceive, locate, count, and touch objects.
FDA Approves Genentech’s Susvimo for Treating Wet AMD
The US Food & Drug Administration (FDA) has approved SusvimoTM, Genentech’s Port Delivery System (PDS) with ranibizumab, for the treatment of wet age-related macular degeneration (AMD).
Susvimo is a refillable capsule the size of a grain of rice which provides continual release of ranibizumab, a protein that blocks the growth of vision-robbing, leaky blood vessels which are the hallmark of wet AMD. The device is implanted near the surface of the eye during a one-time, surgical procedure. The device may only need to be refilled twice per year. The device is not yet available in South Africa.
Patients who have wet AMD should know that if their current Anti-VEGF treatment is not effective, they should consider changing to an alternative treatment. They should discuss this with their Ophthalmologist.
Retina South Africa has done extensive Advocacy work in ensuring that these alternative treatments are fully funded by medical aids. After meetings with Retina South Africa, Discovery Medical Aid now funds these alternate treatments in full, irrespective of the scheme.
Prozac may be the first treatment for Dry Age-Related Macular Degeneration
The repurposing of existing drugs that may prove beneficial in retinal disease receives extensive attention. The possible use of Fluoxetine, the antidepressant commonly known as Prozac, is now a promising drug emanating from this approach. What is of interest is how this was identified.
Traditional approaches to drug development are very expensive and time-consuming. Generally, a new drug takes 10 to 12 years to develop and costs $2.8 billion. Prozac was studied in the laboratory and in animal models. To confirm their findings researchers turned to big data mining. They examined insurance records and found that clients who were being treated with anti-depressants had a substantially lower incidence of dAMD.
Dr Bradley Gelfand from the University of Virginia said “Our identification of the unrecognized therapeutic activity of an existing FDA-approved drug using big data mining, coupled with demonstrating its efficacy in a disease-relevant model, could greatly accelerate and reduce the cost of drug development”.
Dr Gelfand was involved earlier this year in using a similar approach to determine that HIV drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs, may be useful against dry macular degeneration as well. “While we have had a great deal of success with the approach of using real-world patient data, we may have only begun to scratch the surface of finding new uses for old drugs,” said Gelfand, of UVA’s departments of Ophthalmology and Biomedical Engineering.
“It is tempting to think about all the untapped therapeutic potential of medicines sitting on pharmacy shelves.”
Atsena Therapeutics Gene therapy for X-Linked Retinoschisis (XLRS)
XLRS is a retinal disease that causes a splitting of retinal layers leading to significant vision loss. XLRS is caused by mutations in the gene RS1, which produces a protein called retinoschsisin that plays a critical role in the maintenance of the retinal structure and cell-to-cell adhesion.
In XLRS the mothers carry a copy of a defective gene and may pass this on to their sons. The condition is usually diagnosed in boys before the age of 10. XLRS is thought to affect one in 5000 to 25 000 boys.
Previous gene therapy trials showed disappointing results but in this Atsena trial the therapy is injected underneath the retina. This appears to deliver the treatment to the exact spot needed – the cavities in the central retina caused by the splitting of retinal layers. The gene therapy uses a specially designed adeno-associated virus delivery system (AAV.SPR) that can reach the fragile fovea, the tiny pit in the central retina responsible for visual acuity, without an injection in the foveal region.