C.J. Heckman, a professor of physiology at Northwestern University’s Feinberg School of Medicine, agrees: “It is true that a lot of the fatigue seen in FES patients is due to chronic muscle atrophy.” But, he says, “if you could stimulate the muscles in the correct recruitment order repeatedly over time, you could potentially recover a lot of muscle function.” This could help paralysis patients preserve their slow muscle fibers, “which would be a huge deal,” Heckman says. This is because those fibers do a huge percentage of the work muscles do–everything from maintaining posture to typing on a keyboard.
Delp also thinks that stimulation-based exercise could be an important application for optical muscle control, as could helping wheelchair-bound people stand to reach for books or plates in a cabinet. “I’m not super-high on controlling locomotion”–that is, walking–“with either electrical or optical stimulation, though,” Delp says. “It’s an incredibly complicated command-and-control scheme that’s really hard to coordinate.”
In the meantime, Delp and Llewellyn have begun an effort to use a different light-sensitive protein, halorhodopsin, to inhibit motor nerves in mice, with the idea of treating or even curing muscle spasticity, often a serious side effect to brain or spinal injury. Current treatments are far from ideal; doctors may inject botulinum toxin into the affected muscles every few months to paralyze them, use oral medications such as Valium that affect the whole body instead of just the affected muscle, or, in the most severe cases, cut the nerves or tendons of the spastic muscle–a permanent treatment that leaves the patient with no control over that muscle. Delp hopes that genetically engineering the nerves with halorhodopsin might enable people to use light to reversibly relax muscles affected with spasticity.
“I think that’s a great idea for treating spasticity,” says Jerry Silver, a neuroscientist at Case Western. There may be some difficulties along the way, though, he says. Working with Case colleagues, Silver has started a company called LucCell to develop clinical applications of optogenetics. In one company project, scientists are trying to use halorhodopsin and other inhibitory opsins in animal models to turn off the muscle that controls the bladder sphincter; their ultimate goal is to restore bladder function to paralyzed people. Though they have seen some physiological changes in how the sphincter muscle behaves, they haven’t been able to get it to relax enough. “We’re learning it’s easier to turn things on than turn things off,” he says. Still, the team is persisting, looking for better ways to deliver the gene to nerve cells and for ways to increase production of the protein on the cell’s surfaces.
“It all depends on the ability to get the transgene in the right place in the person’s genome without causing problems,” agrees Llewellyn. “It’s the main obstacle.”