A new way to artificially control muscles using light, with the
potential to restore function to muscles paralysed by conditions
such as motor neuron disease and spinal cord injury, has been
developed by scientists at UCL and King's College London.
The technique involves transplanting specially-designed motor
neurons created from stem cells into injured nerve branches. These
motor neurons are designed to react to pulses of blue light,
allowing scientists to fine-tune muscle control by adjusting the
intensity, duration and frequency of the light pulses.
In the study, the team demonstrated the method in mice in which
the nerves that supply muscles in the hind legs were injured. They
showed that the transplanted stem cell-derived motor neurons grew
along the injured nerves to connect successfully with the paralyzed
muscles, which could then be controlled by pulses of blue
light.
"Following the new procedure, we saw previously paralysed leg
muscles start to function," said Professor Linda Greensmith of the
MRC Centre for Neuromuscular Diseases at UCL's Institute of
Neurology, who co-led the study. "This strategy has significant
advantages over existing techniques that use electricity to
stimulate nerves, which can be painful and often results in rapid
muscle fatigue. Moreover, if the existing motor neurons are lost
due to injury or disease, electrical stimulation of nerves is
rendered useless as these too are lost."
Muscles are normally controlled by motor neurons, specialized
nerve cells within the brain and spinal cord. These neurons relay
signals from the brain to muscles to bring about motor functions
such as walking, standing and even breathing. However, motor
neurons can become damaged in motor neuron disease or following
spinal cord injuries, causing permanent loss of muscle function
resulting in paralysis
"This new technique represents a means to restore the function
of specific muscles following paralysing neurological injuries or
disease," explained Professor Greensmith. "Within the next five
years or so, we hope to undertake the steps that are necessary to
take this ground-breaking approach into human trials, potentially
to develop treatments for patients with motor neuron disease, many
of whom eventually lose the ability to breathe, as their diaphragm
muscles gradually become paralysed. We eventually hope to use our
method to create a sort of optical pacemaker for the diaphragm to
keep these patients breathing."
The light-responsive motor neurons that made the technique
possible were created from stem cells by Dr Ivo Lieberam of the MRC
Centre for Developmental Neurobiology, King's College London.
"We custom-tailored embryonic stem cells so that motor neurons
derived from them can function as part of the muscle pacemaker
device." says Dr Lieberam, who co-led the study. "First, we
equipped the cells with a molecular light sensor. This enables us
to control motor neurons with blue light flashes. We then built a
survival gene into them, which helps the stem-cell motor neurons to
stay alive when they are transplanted inside the injured nerve and
allows them to grow to connect to muscle."
The paper, Optical
Control of Muscle Function by Transplantation of Stem Cell-Derived
Motor Neurons in Mice, is published inScience.