Paralyzed mouse legs move with burst of light

Scientists can now control muscles with light. By combining advances from several fields, researchers created neurons that could be activated with light and implanted the cells onto damaged nerves in mice. A brief flash of blue light spurred formerly silent mouse muscles to life, scientists report in the April 4 Science.

The results demonstrate how the disparate fields of stem cell biology and optogenetics, which uses light to activate specially designed cells, might form the basis of new therapies for people with movement problems. One near-term goal of the project is to help people with nerve damage regain the ability to control muscles, says study coauthor Linda Greensmith of University College London. Light-triggered motor neurons might, for instance, reinstate the ability to breathe or swallow in people with amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, who lose control of their muscles.

Greensmith and her colleagues first engineered stem cells so that they would respond to blue light. Next, the team coaxed these cells to form motor neurons, which convey movement signals from the brain and spinal cord to muscles. The team then implanted these light-responsive motor neurons into the thighs of mice, each with one paralyzed leg. The scientists had previously squeezed a section of the nerve that shuttles information between the spinal cord and leg muscles, called the sciatic nerve, to cut off neural signals and paralyze the leg.

The implanted neurons grew long tendrils called axons that reached muscles normally controlled by the nerve. Then, all that was left to do was turn the neurons on. “They were completely silent, and then we shine a blue light on them and they spark to life,” Greensmith says. (An incision on the thigh allowed the light to reach the muscle.)

Different light signals caused different sorts of movement, the researchers found. Short, single pulses of light induced twitches, and longer, repeated pulses caused more sustained muscle contractions.

The ability to selectively control implanted neurons is important, says neurosurgeon and neuroscientist Robert Brownstone of Dalhousie University in Halifax, Canada. “When you think about stem cells, everybody thinks that they’re magic,” he says. “You’re going to put them somewhere and they’re going to fix whatever disease it is that you’re trying to treat.” But those cells are unlikely to form the correct connections. Failing to form the right connections to neurons higher up in the chain of signals from the brain, for instance, would leave motor neurons deaf to the instructions that say which muscles to activate.

Other research, including Brownstone’s, has relied on electrical signals to activate implanted neurons. But electrical stimulation isn’t specific: It activates every neuron around, including those that carry sensory information back to the nervous system, a side effect that may cause discomfort. “The advantage of using light over electrical stimulation is that you can be much more specific in what you’re stimulating,” Brownstone says. “You’re stimulating only the neurons that you put in.”

Many questions remain before the method might be useful in people, Brownstone cautions. In the experiments, the cells were implanted three days after the injury. In contrast, clinicians would probably want to wait between three and six months to see whether a person with a nerve injury recovers before turning to a surgical procedure, he says. It’s also unclear whether the implanted neurons would work over long time periods.

New technology would also need to be developed, including a reliable light source that could consistently deliver the right type and duration of light. Greensmith and her team are also exploring ways to ensure that the implanted motor neurons stay put. This would reduce the risk of cells escaping and forming cancer.

Some diseases such as Lou Gehrig’s might be particularly amenable to light-controlled treatments, says Greensmith. But, she adds, “We’re not saying we’re going to get people up and walking again.” Walking relies on complex patterns of muscle activity. “Breathing, respiration, is a relatively simple function,” she says, “and I think it’s reasonable to say we could target it using this approach.”