Utilization of embryonic stem cells in motor neuron diseases

Douglas A. Kerr M.D., Ph.D.

Assistant Professor Neurology; Molecular Microbiology and Immunology, Johns Hopkins Hospital , Baltimore , MD

We have found that motoneuron-differentiated embryonic stem (ES) cells survive when transplanted into adult rats with a motoneuron injury and that many of the cells resemble mature motoneurons.  In this project, we will determine strategies that facilitate the generation of functional ES cell-derived motoneurons in the injured adult, mammalian spinal cord.  In specific aim one, we will test approaches that remove white matter cues preventing axonal growth of transplanted axons out of the spinal cord.  We will modulate the repulsive activity of myelin in order to allow transplanted axons to extend into the peripheral nervous system.  In specific aim two, we will test approaches that enhance the ability of ES cell-derived motoneurons to further extend axons and allow the formation of functional neuromuscular junctions in vivo.  In order to achieve this we will provide factors that attract motor axons within the distal peripheral nerves and within target skeletal muscle.  These studies will define an important transplantation approach for motoneuron disease such as ALS, SMA and for spinal cord injury and other spinal disorders.