Neuralstem's Human Stem Cells Integrate into Nervous System of Rats with Animal Model of ALS
News Mar 10, 2009
Transplanted human neural stem cells (hNSCs) developed by Neuralstem, Inc. made synaptic contacts with the motor neurons of rats with ALS-like symptoms, a paper published in the current online edition of the Journal of Comparative Neurology reported. This constitutes evidence that the transplanted cells integrated into the nervous system of the host. The rats had a genetic mutation called SOD-1 G93A which gives them a disease similar to ALS in humans.
"This is the first demonstration of transplanted human neurons synapsing, or making mature structural connections, with the rat motor neurons, something which has not been demonstrated before," said Dr. Karl Johe, Neuralstem's Chief Scientific Officer and a study co-author.
"Our earlier work with this ALS model showed that the stem cells delayed onset of the disease and played a neuroprotective role. Now we have clear evidence that they can become an integral part of the rat nervous system that controls the muscles. I would expect these cells to be readily accepted by and integrated into a human nervous system, such as in an ALS or a spinal cord injury patient."
"This is an important milestone for Neuralstem," said Richard Garr, CEO and President. "The underlying basis for 'replacement' therapy is that the cells can integrate into the host to provide function in addition to providing neuroprotection. We are pleased to be the first to demonstrate that our technology passes that test. Our application to begin the first human clinical trial to treat ALS with neural stem cells is currently under review by the FDA. We are delighted that our continuing animal work adds support for the potency of our cells to address progressive neurological degenerations."
In a study conducted at Johns Hopkins Medical Institutions, laboratory-grown human neural stem cells (hNSCs) isolated from a fetal spinal cord region were grafted into the spinal cord of rats with a genetic mutation (SOD-1 G93A) that gives them a disease like a particularly aggressive form of ALS. These rats received live-cell grafts or dead-cell grafts as controls. In addition, four healthy rats (Spague-Dawley) received live-cell grafts to rule out whether or not any cell activity could be attributed solely to ALS in the SOD-1 rats.
The rats had been injected with a tracing material to track and characterize the synaptic connections. 40 days after transplantation, the tissues were examined. In the rats receiving live-cell grafts, a large number of host motor neurons had been contacted by human neurons differentiated from the grafted neural stem cells. This occurred in both the ALS model and healthy rats, indicating that the activity was not a result of the disease.