Story guest authored by Erik Fraunberger, a neuroscience graduate student at the Alberta Children’s Health Research Institute in Calgary, Alberta with contributions by Dr. Mary Sunderland, Director of Research & Education at the Foundation Fighting Blindness.
In 2016, optogenetics is coming out of the laboratory and into the clinic! The first human test of optogenetics will use a gene therapy approach to restore vision to people living with blindness due to retinitis pigmentosa (RP). If the clinical trial with RP is successful, the next step will test if therapy works for people living with advanced dry age-related macular degeneration (AMD). The RP clinical trial is slated to begin later this year, so we have been following the developments closely! Recently, the FFB’s Director of Research and Education, Dr. Mary Sunderland, spoke with Sean Ainsworth, the CEO of RetroSense Therapeutics, which is sponsoring the clinical trial, to learn more about what this means for people living with blinding eye diseases. Mr. Ainsworth confirmed that the trial will begin in the United States in 2016. He also emphasized that bringing these developments to Canada is a high priority for the future.
What you need to know about the optogenetics gene therapy clinical trial for RP
The Phase I/II clinical trial will use a gene therapy approach to evaluate if optogenetics can restore sight to people living with the blinding eye disease retinitis pigmentosa (RP). To start, the trial will enroll 15 patients at the Retina Foundation of the Southwest in Dallas, Texas where Dr. David Birch is the principal investigator. The gene-therapy trial involves delivering the gene RST-001 to the eye with a one-time injection. RST-001 delivers a gene from blue-green algae, which produces a light-sensitive protein. Research suggests that introducing this gene into the eye of people who are blind will restore some vision. To be clear – the aim of the trial is not to replace or fix damaged photoreceptors, which are the eye’s naturally light-sensitive cells that are lost during RP. Instead, the treatment will work by transforming the eye’s non-light sensitive cells into cells that can detect and respond to light. The team’s preclinical research suggests that if the treatment is effective, it may last for many years, perhaps a lifetime.
What is optogenetics?
At one time or another, we have all been stumped by a stubborn problem. I don’t mean just any old problem; I mean the kind of problem that, after hours of intense concentration, you open your mouth wide and shout “AH-HA!” as the lightbulb clicks on in your brain. While that may sound like something out of a cartoon, neuroscientists also think about your brain lighting up in the same way throughout your day but, instead of lightbulbs, picture neurons talking to one another using electrical signals. In fact, “lighting up” the brain to stimulate neuronal function is one of the latest techniques to be used in the field of neuroscience to help us understand how neural circuits communicate. Known as ‘optical genetics’ or ‘optogenetics’, this technique allows scientists to genetically engineer cells to manufacture light-sensitive proteins called rhodopsins, typically found in algae. Cells with these rhodopsins become active in response to light. For example, if neurons that have rhodopsins are exposed to a certain color of light, the rhodopsin will change its shape, which – in turn – changes the activity of the neuron.
This technique, with its strange sounding proteins and futuristic sounding name, is a vision researchers’ dream come true! Before optogenetics, scientists were limited by the methods that were available to study the cells of the eye. Doing what was previously impossible, thanks to optogenetics, is the specialty of FFB-funded scientist, Dr. Gautam Awatramani. His lab, alongside a long list of international collaborators, is currently working to understand how optogenetics can restore sight to individuals with retinal diseases. To date, these methods have been shown to bring back rudimentary vision in animal models. Dr. Awatramani is optimistic about the potential for optogenetics-based therapies for blinding eye diseases, but he also emphasizes that it is important to proceed with caution. This is because there are still important questions about the science that have yet to be answered. For example, he points out that because this approach has never been tested in humans, we are unsure about some of the potential side effects. In the area of emerging therapies, it’s important to remember that clinical trials are happening while scientists are still working out the fundamentals. That’s why it is important to remember that clinical trials are still a kind of experiment – they are not a proven therapy. You can learn more about Dr. Awatramani’s research here.
How will the gene therapy work?
It may sound like science fiction, but optogenetics approaches to treating blindness are becoming a reality! Thanks to innovative research by Dr. Awatramani and others, optogenetics is much more than just a useful lab tool for studying the eye – it is now being applied to the treatment of human retinal disease. The gene therapy developed by RetroSense Therapeutics allows clinicians to directly insert the rhodopsin protein into retinal ganglion cells – the hope is that inserting rhodopsin will allow the retinal ganglion cells to detect light and then communicate that information to the visual part of your brain. In the upcoming clinical trials that focus on RP, the rhodopsin protein will be inserted into the patient’s cells through an injection into the center of the eye. When your eye receives light from the environment, the retinal ganglion cells will be directly stimulated, sending signals along your optic nerve to your brain without any input needed from other parts of your retina. In other words, optogenetics is being used to create a backup visual system in your eye and partially restore lost sight!
With the fast pace of advancements made by optogenetic researchers and the rapid commercialization of gene therapies, it is estimated that optogenetics could become a mainstream treatment option for individuals affected by retinal diseases within the next 5 years. Thanks to FFB donors for helping to drive this research forward!