Neural Stem Cell Clinical Trial
Neuralstem Inc. announced that the first patient had been treated in their new Phase I clinical trial involving “Neural Stem Cells” (NSCs).
In early October, the company Neuralstem Inc. announced that the first patient had been treated in their new Phase I clinical trial involving “Neural Stem Cells” (NSCs). In this trial, four patients with chronic thoracic level injuries (1-2 years post injury) will receive NSC transplants into the injury site. This trial is under the direction of Dr. Joseph Ciacci, MD, UC San Diego School of Medicine and neurosurgeon at UC San Diego Health System. Much of the pre-clinical work with the NSI-566 cells in spinal cord injury was conducted at UC San Diego School of Medicine by Martin Marsala, MD, professor in the Department of Anesthesiology.
As described in our previous newsletters (see Spinal Connections #22, winter 2012), NSCs are stem cells that are already specified to a neural lineage e. They are able to multiply and differentiate into all of the cell types of the nervous system including neurons, astrocytes, and oligodendrocytes. The goal of the treatment being tested in this trial is to inject NSCs into the injury site, where it is hoped that they will develop into a tissue bridge that will allow axons to grow across the injury.
The goal here is a bit different from other ongoing trials of stem cells for spinal cord injury. For example, in the Asterias trial, which continues the one started by Geron, the rationale was to use oligodendrocyte precursor cells (OPCs) derived from embryonic stem cells, which are injected near the site of injury in the hope that they will restore myelin and/or provide growth factors to help repair. In the ongoing trial by Stem Cells Inc., their proprietary NSCs are injected near the injury in the hope that they will develop into nerve cells and glial cells and/or provide growth factors to promote repair.
Neuralstem’s proprietary NSC line is the one that was used for the ongoing ALS trial, in which 30 patients received transplants. This was primarily a safety trial, and no adverse events have been reported so far. A follow-up trial with larger numbers of patients to test efficacy for ALS is being planned.
One cautionary note: Dr. Steward has also been studying NSCs as a means of bridging lesion sites. One surprising discovery this year involves NSCs that were treated with high concentrations of growth factors to promote their survival and expansion. In an experiment in rats, Dr. Steward discovered that about half the rats developed ectopic colonies of cells at long distances from the transplant. For example, following transplants into lesion sites at the thoracic level, colonies of stem cells were found in the cervical spinal cord and the brain. This work was first published in the journal “Cell” in early 2014 and a follow-up article was published in the Journal of Neuroscience in early fall. Dr. Steward is carrying out further studies to determine whether these colonies are harmful or not.
