Optimizing therapeutic use of transplanted embryonic stem cell-derived motoneurons.

Motor neuron diseases, such as amyotrophic lateral sclerosis, result in the death of motor neurons, the specific neurons innervating muscles. Motoneuron death causes muscle denervation resulting in loss of function. This loss of function clinically is demonstrated by progressive weakness and eventually death from respiratory failure. One option to restore muscle functions would be to transplant healthy motoneurons, thus replacing the lost or diseased motoneurons. Stem cells can be induced to transform into motoneurons in culture. These motoneurons are physiologically normal and spontaneously innervate muscle fibers. We have shown that it is possible to transplant motoneurons derived from stem cells into a peripheral nerve and restore muscle innervation, strength and mass. We are suggesting to further study this model of reinnervation and to optimize it for clinical applicability. Once optimized, motoneuron transplants could restore motor functions in individuals affected with motoneuron diseases.