TechnologyEos Neuroscience is in preclinical development for a therapy to restore functional sight to patients blind from photoreceptor diseases such as retinitis pigmentosa (RP) and macular degeneration (AMD) and is developing treatments for other neurodegenerative diseases. Our treatments are based on the core technologies of optogenetics and gene therapy.
For over a hundred years, electrodes have been used to activate nerve cells – first out of scientific curiosity, then as a major clinical tool with applications as varied as pacemakers for heart conditions and deep brain stimulators to treat Parkinson’s disease.
Electrical stimulation is limited, however, because it is not specific. It does not target specific cells and pathways within a volume of tissue, but rather like a flashlight shining into a dark room, an electrode activates all the neurons within its vicinity. Eos Neuroscience addresses this limitation with light-sensitive proteins (opsins) that are used to selectively sensitize specific types of neurons to light. Like nanoscale solar cells, sensitized neurons respond electrically to light creating an optical interface to the brain, spinal cord, or peripheral nervous system. Using common gene therapy techniques, Dr. Ed Boyden and collaborators developed a method to express these proteins in specific cell types within very heterogeneous tissue. Because the nervous system contains hundreds of different types of neurons, each with different computational properties and different potential for correcting disease states, this specificity in expression provides a true advantage over other methods of stimulation.
This field is now commonly called optogenetics. The figure below shows the electrical response of actual neurons to light input after being treated with various light activated proteins including Arch and Mac, which were recently found by the Boyden lab at MIT to very effectively silence neural activity in the presence of light of various colors. This new toolbox is in use by hundreds of research labs around the world.
In photoreceptor diseases, such as macular degeneration and retinitis pigmentosa, the eye maintains the ability to process visual input but loses the ability to capture light.
In addition, the circuitry of the retina is complex. The retina is an array of one million independent, tightly grouped data channels, comprised of four major different types of neurons (photoreceptor, bipolar, amacrine, ganglion). These neurons are grouped together in antagonistic, ON and OFF networks that respond to increments or decrements of light.
Traditional therapeutic approaches are ill-suited to handle this level of complexity. Pharmaceuticals are unable to help once the majority of photoreceptors are lost. Electrical stimulation is currently limited in channel resolution and, more importantly, indiscriminately stimulates across cell types and ON and OFF channels. Gene replacement therapies are promising, but ineffective once photoreceptors are lost, and are each limited to treating just one of the 180+ mutations that can lead to photoreceptor disease.
Eos believes that a better answer is an optogenetic approach. Our therapy enables the expression of a light activated protein in retinal bipolar cells, a specific subpopulation of neurons in the retina that receives input from photoreceptors. This therapy allows the eye to again be activated by light, even though the natural photoreceptors are gone. This therapy has achieved proof of concept in mice and is in preclinical development to treat blindness caused by human retinitis pigmentosa and macular degeneration.