Neural & Glial precursors & LIF therapy in a model of diffuse axonal injury/brain trauma

Funding Type: 
Early Translational III
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Traumatic brain injury (TBI) is a global epidemic leading to poor outcome in 50% of mostly young individuals. Yearly in the US, 1.7 million TBIs occur; in [REDACTED] TBI causes 235/100,000 hospital admissions. The financial burden is estimated over $60 billion/year in the US and $8.6 billion/year in [REDACTED]. Diffuse TBI affects up to 70% patients with head injury, causing progressive axonal degeneration, myelin degradation and permanent deficit. Currently, there are no effective treatments to halt delayed brain damage and neural stem cell therapies offer great potential. The partnership of 2 successful neurotrauma groups in CA and [REDACTED] aims to establish a novel stem cell transplantation therapy in a well characterized diffuse axonal injury model. Importantly, diffuse axonal injury is a significantly different target than the focal contusion model of TBI currently in CIRMs portfolio. Clinical grade human neural stem cells, neuronal restricted progenitors (NRP) and/or glial restricted progenitors (GRP) derived from ES cells will be transplanted into injured brain; concurrent infusion of LIF is expected to enhance survival of transplanted cells, promote axonal repair and remyelination. Validated neurological measures will be used to determine therapeutic efficacy, including tests similar to those conducted in humans, such as diffusion tensor MRI imaging to measure tissue damage. This study will delineate a new cell therapy paradigm for the treatment of patients with diffuse TBI.

Statement of Benefit to California: 

This project has the potential to develop a new therapeutic paradigm for the treatment of patients with traumatic brain injuries. TBI has been called a silent epidemic, affecting more people than breast, lung, prostate, brain, and colon cancer combined. Currently no therapies can reverse the detrimental effects of brain injury, leaving mostly young patients with permanent disabilities. Our goal of specifically targeting diffuse brain injury (the most abundant form in humans), has critical implications for the benefit of this large patient population globally. This study sees the partnership of two eminent neurotrauma groups in CA and [REDACTED] that merge decades of experience in neurotrauma research and expertise bring stem cell therapies to trial. The established collaborations of these PIs with local specialists consolidate an interdisciplinary approach adding huge credentials to this study. In [REDACTED], the proximity of the team with a major trauma centre where specialist clinicians have years of experience in conducting clinical trials on head trauma patients, sees an authentic opportunity for the future translation of a revolutionary cell based therapy in patients with brain trauma. At 12% of the US population, over 200,000 California’s per year are projected to suffer a TBI; with an economic cost to the state of well over 7 billion dollars annually. Even a small improvement in outcome would benefit patients, their families and the economic position of CA and [REDACTED].