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New Devices Promise Electrical Control of Neural Growth

Electrical activation of the nervous system is used to restore function following neurological injury or disease. These devices, described as neural prostheses or as functional electrical stimulation, use electrical stimulation to produce actions such as muscle contraction, as in motor prostheses, or the perception of sound, as in cochlear prostheses.
Neuronal activity also has profound influences on cellular processes in the nervous system including gene expression, synapse formation, and modulation of the strength of synaptic connections between neurons.

The results of two recent studies demonstrate that electrical activity can also control the genesis of new neurons from stem cells and control the patterns of growth of neurons extending from the cortex to the spinal cord. These results are possible harbingers of a new generation of neural prostheses that influence nervous system function by control of activity-dependent cellular processes. Already, at least two neurotechnology companies are exploiting activity-dependent plasticity to enhance function following neurological injury.

Stem cells are a promising approach to restoration of neuronal function, but control of cell differentiation (i.e., convincing stem cells to turn into neurons) remains a challenge. Deisseroth and colleagues from Robert Malenka's lab at Stanford University recently reported in the journal Neuron that electrical activity acts directly on neural stem/progenitor cells (NPCs) to promote production of neurons. First, they showed application of either depolarizing stimuli or excitatory neurotransmitters in a culture of NPCs from the hippocampus increased neuron production and increased the number of cells that exhibited functional synaptic connections. Conversely, the application of agents that blocked either membrane ion channels or neurotransmitter receptors reduced intrinsic neurogenesis.

Next, they demonstrated that similar agents that either blocked membrane ion channels or reduced neuronal activity reduced neurogenesis in living animals, and, conversely, that neurogenesis in vivo was enhanced by an agent that activated membrane ion channels. These results demonstrate that increased activity can enhance the birth of new neurons, and suggest that electrical stimulation may promote the replacement of neurons in the damaged nervous system.

A second report, in The Journal of Neuroscience, indicates that electrical stimulation can promote the growth and connection of axons projecting from the brain to the spinal cord. During normal development certain of the connections of these axons to spinal targets, especially those on the ipsilateral side of the spinal cord, are eliminated to yield a selective pattern of termination. Salimi and Martin from Columbia University found that two hours per day of intermittent electrical stimulation for a period of 2-3 weeks prevented the elimination of the cortex to spinal cord connections and produced robust patterns of termination on both the contralateral and ipsilateral sides of the spinal cord. These results demonstrate that electrical stimulation can influence the growth of developing neurons extending processes (axons) from the cortex to the spinal cord. Normal neuronal development may represent a roadmap to follow for techniques to restore CNS function after trauma, and electrical stimulation may provide a means to promote regrowth and reconnection of axons following spinal cord injury.

Two neurotech companies are activity pursuing development and evaluation of novel therapies that seek to exploit activity-dependent processes within the nervous system. Northstar Neuroscience in Seattle, WA is currently sponsoring clinical trials to evaluate the safety and effectiveness of cortical stimulation to promote recovery of motor function following stroke. The approach involves implantation of a device for the delivery of electrical stimulation intended to promote the expansion of the neural network controlling limb function. Preclinical work presented at last year's Society for Neuroscience Annual Meeting, and published in a special issue of the journal Neurological Research last December, demonstrated that cortical stimulation coincident with physical rehabilitation led to both function and anatomical changes that exceed those that occurred following physical rehabilitation alone.

Restorative Therapies, Baltimore, MD, is a start up pursuing design, manufacture, and marketing of restorative therapy products for people with neurological impairment. The approach is based on activity-dependent rehabilitation strategies and builds upon the work of John McDonald from Washington University in St. Louis, MO. McDonald's results suggest that physical therapy, assisted by electrical stimulation, can promote restoration of function following spinal cord injury. RTI's plans for commercializing this patented therapy have the initial product offering being available by mid 2005. Restorative Therapies is being led by neurotech veteran Andrew Barriskill, formerly of Cochlear Ltd.'s Neopraxis unit, and is currently raising equity through a private placement.

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