A genetic tweak can make light work of some nervous disorders. Using flashes of light to stimulate modified neurons can restore movement to paralysed muscles. A study demonstrating this, carried out in mice, lays the path for using such “optogenetic” approaches to treat nerve disorders ranging from spinal cord injury to epilepsy and motor neuron disease.
In the latest study, a team led by Linda Greensmith of University College London altered mouse stem cells in the lab before transplanting them into nerves in the leg – this means they would be easier to remove if something went wrong.
Muscles in action
Greensmith’s team inserted an algal gene that codes for a light-responsive protein into mouse embryonic stem cells. They then added signalling molecules to make the stem cells develop into motor neurons, the cells that carry signals to and from the spinal cord to the rest of the body. They implanted these into the sciatic nerve – which runs from the spinal cord to the lower limbs – of mice whose original nerves had been cut.
After waiting five weeks for the implanted neurons to integrate with the muscle, Greensmith’s team anaesthetised the mice, cut open their skin and shone pulses of blue light on the nerve. The leg muscles contracted in response. “We were surprised at how well this worked,” says Greensmith.
To make the technique practical for use in people, the researchers are developing a light-emitting diode in the form of a cuff that would go around the nerve, which could be connected to a miniature battery pack under the skin.
They are also trying to develop an alternative to using embryonic stem cells, as these would require the recipient to take drugs to stop their immune system attacking the transplanted neurons. Instead the team is working with induced pluripotent stem cells, cells that have been reprogrammed to behave like embryonic stem cells, but can be made from a small sample of the intended recipient’s own skin.
The team’s first goal is to help people with motor neuron disease who lose the ability to control their breathing muscles. “Walking involves contracting about 40 different muscles in complex sequences,” says Greensmith. “Breathing is very simple – one muscle contracts and relaxes.”
They plan to test the restoration of breathing ability in pigs, and are developing a pacemaker that could repeatedly illuminate the phrenic nerve in the chest, which controls the diaphragm.
Other groups are exploring different therapeutic applications of optogenetics, including treatments for epilepsy and Parkinson’s disease.
Stimulating neurons with light can restore movement to paralysed mouse muscles; a step towards using "optogenetic" approaches to treat nerve disorders.
Stem cells and light restore paralysed muscles