Light Switch for Bladder Control

A startup is developing molecular "light switches" for clinical use.

A startup out of Case Western Reserve University in Cleveland plans to commercialize molecular "light switches," a genetic technology that has rapidly taken root in the research world. Initially developed in 2006, the technology involves injecting small snips of DNA into living animals to allow specific neurons to be controlled with light. The company, called LucCell, will focus first on developing therapies to restore bladder control in paralyzed people.

Light control: A spinal cord neuron (green) carrying the photosensitive channelrhodopsin protein—when hit with light, the cell sends a signal to the diaphragm muscle, helping a paralyzed rodent to breathe. Credit: Society for Neuroscience.

The effort signals a growing interest in developing these unique research tools for clinical use. Ed Boyden, a neuroscientist at MIT and one of the original inventors of the technology, formed a startup earlier this year to develop new therapies for blindness. (Boyden is a columnist for Technology Review.) "It's exciting to see interest in pushing this technology, which was considered a powerful basic science tool, into the clinic," says Boyden.

The molecular light switches contain a gene for a light-sensitive protein derived from algae, called channelrhodopsin-2, as well as molecular instructions that limit its expression to a specific subset of cells. The gene is delivered to the target tissue via a virus, much like in gene therapy.Once taken up into the cell, the DNA triggers production of a protein that activates the cell when exposed to light.

The approach has become one of the hottest new tools in neuroscience, and it is being used across the globe to study psychiatric and neurological disorders such as depression, addiction, and epilepsy, as well as normal brain functions such as movement and memory.

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LucCell will focus primarily on breathing and bladder function in paralyzed people. In both cases, signals from the brain can no longer reach the relevant muscles. The idea is to make the neurons controlling those muscles light-sensitive; the cells could then be turned on or off with an implanted light source. "We believe the light-switch technology could be most readily applied to those targets because they require just one or two muscles -- the diaphragm for breathing, and the external sphincter for bladder function," says Jerry Silver, a neuroscientist at Case Western and president of LucCell. "I'm really optimistic that we can help people." Silver is running the company with two colleagues at Case Western, Stefan Herlitze and Evan Deneris.

Last year, Silver and his collaborators showed that channelrhodopsin could be used to restore breathing function in paralyzed rodents. Researchers first recreated a high-level spinal cord injury in rodents, paralyzing half of the diaphragm. They then injected the switch into the spinal cord, near the nerves that control the crippled muscle. Shining light on those cells triggered muscle contractions in the diaphragm. "The paper shows remarkable recovery of breathing function on the side of the animal with impaired function that lasted for a day even after light was turned off," says Silver.