Home > Amyotrophic Lateral Sclerosis > Research News > Combining two brand new technics to restore muscle function

Optogenetically-Controlled Restoration of Muscle Function in ALS to control breathing in ALS patients without the need for mechanical ventilation

Greensmith Bryson Group image

This avant-guarde project is managed through a collaborative work between University College London, Dr Barney Bryson in the team of Pr Linda Greensmith and Kings College London, Dr Carolina Barcellos Machado in the team of Pr Ivo Lieberam.



The project was selected during the 2010 call for projects, first results being recently published in Science.

Second phase of the project is starting now through a co financing with Motor Neuron Association. They have developed a completely novel strategy to restore motor function in ALS patients that exploits the recently developed technology of optogenetics.

They have shown that muscle function can be restored and finely controlled by engraftment of embryonic-stem cell derived motor neurons (ESC-MNs) which express the light-gated ion channel, channelrhodopsin (ChR2).

Greensmith neurones réinnervés

Image of transplanted embryonic stem cell-derived motor neurons within the sciatic nerve; the transplanted neurons have been labelled with a functional marker of mature motor neurons (choline acetyltransferase; red) and the channelrhodopsin-2 protein (green), which enables the neurons to be controlled optogenetically ie by blue light.


At this time point, the nerve in the mid-thigh region was exposed and a blue light-source was used to ‘optogenetically’ activate the transplanted motor neurons, which resulted in finely controlled muscle contractions.

The schematic illustrates the transplantation of embryonic stem cell-derived motor neurons  into specific branches of an injured sciatic nerve. After 35 days, the transplanted motor neuron axons grow towards  the muscles in the hind-limb to reinnervate them.

Greensmith Schéma muscle

Peripheral engraftment ofthese ESC-derived MNs in vivo into a denervated nerve can not only replace lost motor axons but, importantly, optical stimulation can enable these neurons to control and restore muscle function.

Control of the diaphragm muscle and maintenance of respiratory function in ALS patients using an optical pacemaker presents the most immediate clinical application for this strategy.

Greensmith Schéma Diaphragm

Diagram of the ultimate clinical application of this research : Schematic representation of light-activated motor neuron transplants combined with an implantable optical pacemaker, which will enable ALS patients with compromised respiratory function to breathe without the need for mechanical ventilation.



Pr Linda Greensmith departement website