Human Neural Stem Cell Transplantation in Traumatic Brain Injury

If you believed everything you saw in the movies, you would think that a gunshot wound to the head almost always results in death.  However, real-life data shows that 42% of victims survive penetrating head wounds.  The 2011 shooting of Congresswoman Gabrielle Giffords provides a recent, high-profile example.  For these people and their families, the health and economic burdens resulting from traumatic brain injury are immense.  Restorative treatments aimed at helping people gain greater independence have the potential to greatly improve quality of life.  Unfortunately, no effective, FDA-approved treatments exist, although some animal experiments have shown promise.       

Drs. Ross Bullock, Shyam Gajavelli, and Marcus Spurlock, along with their team of researchers at The Miami Project, are evaluating the restorative potential of human neural stem cells in a rat model of head injury.  After being transplanted near the area of damage within the brain, cells grew and developed in to neural cells, and some beneficial effects were seen in learning and memory.  To rapidly translate their findings, a strong collaboration was established between the Miami Project, Walter Reed Army Research Institute, and Neuralstem Inc.  Collaborators have already completed similar studies in larger animals, and safety profiles of the cells are being evaluated in relation to head injury.  Since these particular human brain cells are already approved by the FDA for use in clinical trials for stroke, spinal cord injury and ALS, they could be moved more quickly to clinical trials for head injury patients.  Thus, this therapy has the potential to become a first in brain neurorestorative surgical treatment.

The study, published in the Journal of Neurotrauma, is entitled, Amelioration of penetrating ballistic-like brain injury induced cognitive deficits after neuronal differentiation of transplanted human neural stem cells, was led by Ross Bullock, M.D., Ph.D.  These are the first data from the 4-year proof-of-concept research program, funded by the United States Department of Defense, for NSI-566 in traumatic brain injury.

“These data on NSI-566 are encouraging, particularly since researchers have long been challenged to achieve durable engraftment and survival of neural stem cells after transplantation,” said Dr. Bullock.   “No long-term treatment beyond physical therapy is currently available to restore cognition after a traumatic brain injury.  Transplantation of stem cells into the injured brain may allow a unique replacement therapy and fill a significant medical need.”

Researchers transplanted NSI-566 into rats 7-10 days after PBBI.  The rats were immunosuppressed to enable survival of NSI-566 neural stem cells.  Robust engraftment with evidence of prominent neuronal differentiation was observed after 4 months, and axons from grafted cells extended a significant distance from the graft site along host white matter tracts.

“These data continue to support our research and development platform. The results provide additional insight into our proprietary regionally specific stem cells and their potential benefits in nervous system disorders,” said Karl Johe, Ph.D., Chief Scientific Officer, Neuralstem.  “We look forward to additional preclinical data from this collaboration with Dr. Bullock’s group to support the potential use of NSI-566 in traumatic brain injury.”

View article on PubMed