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Using light to get muscles moving

Did you ever think photosynthetic algae would throw light on the problem of helping paraplegics walk before they run? A new study in Nature Medicine illustrates basic science's potential to lead to medically valuable results.

Optogenetics, invented at Stanford by psychiatrist and bioengineer Karl Deisseroth, MD, PhD, is a research technology in which the gene for a light-sensitive protein found in algae is inserted into the genome of experimental animals (mice).

The result is that the surfaces of nerve fibers in those otherwise normal mice's brains wind up dotted with this protein. In turn, the protein responds to certain wavelengths of light by triggering electrical impulses in the nerve fibers on which they sit.

The technique allows scientists such as Deisseroth to use light to precisely probe the functions of very specific groups of nerve cells in the brain, leading to all kinds of insights about the nature of syndromes such as Parkinson's disease.

Now, for the first time, optogenetics has been adapted for use with the skeletal musculature. It turns out that, in the same experimental mice, the motor nerves that exit the spinal cord and make contact with muscle fibers are also coated with the light-sensitive, impulse-triggering protein.

The problem of restoring physiologically normal movement in paraplegics is something bioengineer Scott Delp, PhD, has been working on for some time. Attempts to do this using electrical impulses to trigger the firing of motor nerves have met with partial success. But electrical stimulation triggers nerve firing in the wrong sequence: powerful fast-twitch muscle fibers first, fine-movement-coordinating slow-twitch muscle fibers last. The result: extremely jerky motion, and rapid fatigue.

Mike Llewellyn, PhD, of Delp's lab designed a tiny optical cuff that beamed intense LED light at the mice's sciatic nerves. This activated nerves in such a way that slow-twitch muscle fibers contracted first, just as they do in normal muscles.

A big obstacle to moving this work rapidly into the clinic is the need to demonstrate the safety of gene therapy on humans. But that ought to be easier to accomplish in an experiment involving arms and legs than in one involving brains.

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