Restoring useful function to complete and permanently denervated skeletal muscles

Skeletal muscles regulating movements such as walking, hand grasping, breathing and swallowing are controlled by cells in the nervous system called motoneurons. Motoneurons controlling individual muscles often die after a spinal cord injury. Motoneuron death causes the affected muscles to become paralyzed because they are permanently disconnected from the nervous system. There is currently no known way to restore meaningful function to these muscles. However, previous studies from my lab showed that muscles can be genetically modified to express a light activated protein known as channelrhodopsin 2 (ChR2). Muscles expressing ChR2 contract when exposed to bright light even when there are completely disconnected from the nervous system. Here we propose that this technology can be further advanced to restore function to paralyzed muscles without the use to genetic manipulation. For example, paralyzed skeletal muscles will be injected with muscle stem cells that were forced to express ChR2 using viral technology. We propose that the muscles stem cells will become incorporated with the paralyzed muscles causing them to express ChR2. Once they express ChR2, the targeted skeletal muscles can be controlled in a meaningful way with small light emitting diodes (LEDs). We believe these studies will lay the foundation for using this new technology to restore meaningful movement such as hand grasping, or breathing, to individuals whose hand muscles or diaphragm were permanently paralyzed due to motor neuron death after a spinal cord injury.