The MND Association is proud to support the brightest minds of MND research. Outside of general healthcare and biomedical project grants that are usually awarded to senior researchers, we also offer opportunities to young researchers – these take the form of PhD studentships and fellowships.
Fellowships are awarded to post-doctoral researchers who are able to support a research project as the leading investigator. Depending on their qualifications, the fellowship can either be clinical (for healthcare professionals) or non-clinical (for researchers with purely academic background). In the last round of non-clinical fellowship applications in October 2016, the MND Association awarded a senior fellowship to Dr Barney Bryson of University College London. In his upcoming project, due to start in August 2017, he will follow up on the findings he found together with his team, led by Prof Linda Greensmith.
Using light to move muscles
The idea behind Dr Bryson’s innovative project is that we can use a stimulator that emits light to create electrical signals in motor neurones (that form connections with affected muscles), rather than attempting to create long nerve connections between the muscles and the spinal cord.
We could think of this as creating a new electrical circuit from a power supply to an electric motor after lots of the wires have been damaged. Instead of reconstructing the long wires from the power supply to the motor, the researchers can directly plug in a new device that is capable of controlling the motor (or muscle in their case).
How can we use light to move muscles?
To control muscle movement by blue light, the researchers first had to create specially-modified stem cells from mice, from which specialized motor neurones could be generated. These motor neurones produce a specific neurotrophic factor and a gene that is sensitive to light, which enables them to survive longer after their implantation, and their activity to be controlled using pulses of light, respectively.
After these cells had been constructed, they were implanted into damaged sciatic nerves (one of the nerves controlling movements of the leg) in mice. Due to the survival-promoting neurotrophic factor, the implanted motor neurones were able to establish strong connections (innervation) with an atrophied muscle. Once innervated, an optical stimulator was then used to activate the transplanted motor neurons, creating electrical impulses that directly led to contraction of the connected muscles. They are now using a sophisticated implantable optical stimulator that was developed by Prof Ada Poon at Stanford University (Montgomery et al., 2015).
How will this work be followed up now?
Much work still remains to be done before this approach could work effectively in human patients, which is a major focus of Dr Bryson’s fellowship project. Specifically, he will investigate how to best promote innervation of muscle fibres once the motor neurones are implanted. This will be done by closely observing the process of innervation in a laboratory dish and identifying the factors that promote best neurone-muscle connectivity. This part of the project is of great importance as strong connections are necessary for the muscles to receive an electrical instruction to contract.
How will this help people with MND?
While still at an early, pre-clinical stage, this project has a potentially immense impact for people with MND as it could re-establish electrical signals to the diaphragm, our main breathing muscle. When this muscle is affected, the person’s breathing ability deteriorates and an artificial way to support breathing has to be implemented (eg non-invasive ventilation). By implanting light-sensitive motor neurones to the phrenic nerve, which controls the diaphragm muscle, an optical stimulator emanating blue light could then directly control contractions of this muscle, greatly improving the person’s ability to breathe as a consequence. The hope is to also use this mechanism for peripheral muscles in order to improve person’s movement abilities.
“This exciting project represents the next step in the continued development of an entirely novel strategy to overcome the progressive loss of ability to control specific muscles that occurs in MND.
“Although this future therapy is not aimed at preventing or slowing down the progressive loss of motor neurons that occurs in MND, it effectively circumvents the problem and could enable specific muscle functions and movements to be restored in an artificial manner in MND patients whose muscles have been paralysed, thus improving their quality of life.” Dr Barney Bryson
To find out more about MND Association-funded clinical fellowship projects, you can read about Dr James Bashford’s project investigating muscle fasciculations, or Dr Pietro Fratta’s project looking at understanding the role of RNA in MND.
Many thanks to Dr Bryson for his input and comments on this article.
To read more about the development of the optical stimulator that Dr Bryson uses, see the original research paper by Montgomery et al. (2015).