Designing A Neural Prosthesis Using Light Activated Nerve Stem Cells

Dr. Ivo Lieberam Lecturer, MRC Centre for Developmental Neurobiology King's College London New Hunt's House, Guy's Hospital Campus London, SE1 1UL Interview with:
Dr. Ivo Lieberam
Lecturer, MRC Centre for Developmental Neurobiology
King’s College London
New Hunt’s House, Guy’s Hospital Campus
London, SE1 1UL UK What are the main findings of the study?

Dr. Lieberam: In this study, which my group undertook in collaboration with Linda Greensmith’s group at University College London, we found that we could artificially control muscle activity using transplanted stem cell-derived nerve cells as an interface between an opto-electronic pacemaker and paralysed muscle in mice. The nerve cells were equipped with a molecular photosensor, so that they could be activated by light. We think that long-term, this technology may be used in neural prosthesis designed to re-establish relatively simple motor functions, such as breathing or swallowing, in patients suffering from spinal cord injury or neuromuscular diseases such as Motor Neuron Disease. Were any of the findings unexpected?

Dr. Lieberam: While we had to solve a number of technical problems along the way, we knew from the start that light-activation of grafted nerve cells, and muscle control through the graft, might be possible from two earlier pioneering studies: Rob Brownstone’s group at Dalhousie University/Canada had previously shown that stem cell-derived nerve cells can survive in peripheral nerves in mice and connect to muscle, and Scott Delp’s group (Stanford University/USA) had used a light-activated genetic probe to control muscle contractions in transgenic mice. In our study, we merged these two strands of research, and to our delight, it turned out that transplanted stem cell-derived nerve cells can be activated with the photosensor, and we were able to control fine-tuned rhythmic muscle contractions via the neural graft. What should clinicians and patients take away from your report?

Dr. Lieberam: We think that our approach holds a lot of promise, and we are keen to move on from the proof-of-principle stage towards pre-clinical trials. However, we would like to caution clinicians and patients that it may take several years and a lot of work until we can start to apply this technology to humans. In addition, the muscle pacemaker device we are developing will initially be suitable only for restoring basic motor functions, not complex ones like walking. The reason for this is that while walking may seem like an every-day activity, it is in fact quite complicated: In each leg alone, about 40 muscles need to be activated in a defined sequence during each step cycle, and constant corrections based on sensory feedback are required. What recommendations do you have for future research as a result of this study?

Dr. Lieberam: We believe that over the next two decades, light-gated genetic switches, such as the one we use to activate nerve cells connected to muscle, may evolve from a research tool in basic neuroscience into molecular therapeutics which will be used to restore defective neural circuits in humans. The medical applications of these so-called ‘optogenetic’ probes will not be limited to muscle control, but may also proof effective in other neurological conditions, such as epilepsy.


Optical Control of Muscle Function by Transplantation of Stem Cell–Derived Motor Neurons in Mice

J. Barney Bryson, Carolina Barcellos Machado, Martin Crossley, Danielle Stevenson, Virginie Bros-Facer, Juan Burrone, Linda Greensmith, and Ivo Lieberam

Science 4 April 2014: 344 (6179), 94-97. [DOI:10.1126/science.1248523]