Nerves made to express proteins that can be activated by light can produce limb movements that can be adjusted in real-time, using cues generated by the motion of the limb itself, according to MIT researchers. This optogenetic technique has only been tested on animals at this point, but it could eventually be used to restore movement in patients with paralysis or to treat patients with movement disorders.

“Most people are using optogenetics as sort of a tool to learn about neural circuits, but very few are looking at it as a clinically translatable therapeutic tool as we are," said Shriya Srinivasan, a PhD student in medical engineering and medical physics at the MIT Media Lab and the Harvard-MIT Program in Health Sciences and Technology.

Srinivasan and her colleagues envision the technology first being used to restore motion to paralyzed limbs or to power prosthetics, but they say it also has the potential to restore limb sensation, turn off unwanted pain signals, or treat spastic or rigid muscle movements in neurological diseases such as amyotrophic lateral sclerosis (ALS).

“Artificial electrical stimulation of muscle often results in fatigue and poor controllability. In this study, we showed a mitigation of these common problems with optogenetic muscle control,” said Hugh Herr, who led the research team and heads the Media Lab’s Biomechatronics group. “This has great promise for the development of solutions for patients suffering from debilitating conditions like muscle paralysis.”

The group's research paper was published in the Dec. 13 issue of Nature Communications.

Doctors already use electrical nerve stimulation to treat patients with spinal cord injury, and to improve muscle conditioning in people with muscular degenerative diseases. The downside of electrical stimulation is that it can quickly fatigue muscles and is difficult to target precisely. That's why scientists like Srinivasan and Maimon are looking for alternative methods of nerve stimulation.

Optogenetic stimulation relies on nerves that have been genetically engineered to express light-sensitive algae proteins called opsins. These proteins control electrical signals such as nerve impulses — essentially, turning them on and off — when they are exposed to certain wavelengths of light.

Using mice and rats engineered to express these opsins in two key nerves of the leg, the researchers were able to control the up and down movement of the rodents’ ankle joint by switching on an LED that was either attached over the skin or implanted within the leg.

This is the first time that a “closed-loop” optogenetic system has been used to power a limb, the researchers said. Closed-loop systems change their stimulation in response to signals from the nerves they are activating, as opposed to “open-loop” systems that don’t respond to feedback from the body.

In the case of the rodents, different cues including the angle of the ankle joint and changes in the length of the muscle fibers were the feedback used to control the ankle’s motion. Srinivasan said it's a system that "in real time observes and minimizes the error between what we want to happen and what’s really happening.”

In electrical systems, large-diameter axons are activated first, along with their large and oxygen-hungry muscles, before moving on to smaller axons and muscles. Optogenetic stimulation works in the opposite way, stimulating smaller axons before moving on to bigger fibers.

“When you’re walking slowly, you’re only activating those small fibers, but when you run a sprint, you’re activating the big fibers,” Srinivasan said. “Electrical stimulation activates the big fibers first, so it’s like you’re walking but you’re using all the energy it requires to do a sprint. It’s quickly fatiguing because you’re using way more horsepower than you need.”

Researchers are used to seeing systems perform really well and then fatigue over time, but Srinivasan said that when the optogenetic system fatigued and the team kept doing experiments for extended periods of time, the system recovered and started performing well again. This rebound, which was unexpected, has to do with how opsin activity cycles in the nerves, the group concluded.

With less fatigue involved, the optogenetic system might be a good future fit for long-term motor operations such as robotic exoskeletons that allow some people with paralysis to walk, or as long-term rehabilitation tools for people with degenerative muscle diseases, Srinivasan suggested.

The next steps in the research include experimenting with the best ways to deliver light to nerves deep within the body and finding ways to express opsins in human nerves safely and efficiently.