Developing human-pluripotent-stem-cell-derived neuron regeneration therapy for spinal cord repair

Funding Type: 
Disease Team Therapy Planning I
Grant Number: 
DR2-05339
Investigator: 
ICOC Funds Committed: 
$0
oldStatus: 
Closed
Public Abstract: 
There is a large unfulfilled healthcare need to provide optimal regeneration treatment options for the damaged or lost nerve tissue in spinal cord injury (SCI)-resulted paralysis. Given the complex nature of SCI, to date, there is lack of a single conventional strategy that will lead to a dramatic functional improvement. Despite intense interest in developing cell-based therapies, the inhibitory non-neurogenic environment and loss of axonal connections after SCI pose many obstacles to nerve regeneration. While neural stem cells are multipotent, following transplantation into the injured spinal cord, engrafted cells almost always differentiate predominantly towards a non-neuronal cell type. For spinal cord regeneration, however, it is important that the nerve tissue regenerate in order for the lost function to be regained. The pluripotent human embryonic stem cells (hESCs) are genetically stable, proffering an ideal source for developing cell-based therapy to provide optimal regeneration treatment options for the damaged or lost nerve tissue in SCI that have been lacking. However, how to channel the broad differentiation potential of human pluripotent cells efficiently and predictably to specialized functional cells has been a major challenge for clinical translation. This proposal overcomes some major obstacles in translational biology by developing novel strategies for direct control and modulation of hESC pluripotent fate with small molecules into a large supply of human central nervous system neuronal progenitors (hNPs) for nerve regeneration in order to achieve efficient functional recovery in spinal cord repair in the clinical setting. In this project, clinically-suitable hNPs induced direct from hESCs will be filed to obtain FDA approval of manufacturing and transplanting into both acute and chronic SCI patients for early phase clinical studies. Clinical trials will be designed to evaluate primarily safety in humans as well as provide preliminary evidences of therapeutic mechanism and clinical efficacy for nerve regeneration and functional improvement that could lead to more definitive clinical efficacy studies. There is no other treatment option available at present time to improve the neurologic and motor functions in SCI-resulted disability, particularly in patients at the chronic stage. The proposed disease team therapy development project will provide safe and effective hESC-based regenerative therapy as optimal treatment options for restoring the lost tissue and function in both acute and chronic SCI patients. Fulfilling the goal of this project will lead to a significant improvement in SCI patient care, potentially a dramatic functional improvement or recovery. The outcome of this project will have a transformative impact on improving the function, wellness, and overall quality of life for SCI patients, extending independent healthy life and reducing the burden of illness and disability.
Statement of Benefit to California: 
Spinal cord injury (SCI) typically results in permanent disability. Given the complex nature of SCI, to date, there is lack of a single conventional strategy that will lead to a dramatic functional improvement. Approximately 250,000 people in the United States have SCI, with around 12,000 new cases reported each year. The costs of lifetime care for one patient with SCI-resulted disability range from $700,000 to $3,000,000. There is an unmet medical need to provide cures or treatments to ease both the physical and financial burdens of patients with SCI-resulted disability. Even seemingly small improvements in function may have a large impact on a patient’s life. Pluripotent human embryonic stem cells (hESCs) are genetically stable, proffering an ideal cell source for developing cell therapies to provide next generation cell-based therapeutic solutions for unmet medical challenges in some major health problems. However, how to channel the broad differentiation potential of human pluripotent cells efficiently and predictably to specialized functional cells has been a major challenge for clinical translation. This proposal overcomes some major obstacles in translational biology by employing a novel approach to derive a large supply of clinically-suitable human neuronal progenitors from pluripotent hESCs for nerve regeneration and function restoration in spinal cord repair. There is no other treatment option available at present time to improve the neurologic functions in SCI-resulted disability, particularly in patients at the chronic stage. This project enables the translation of groundbreaking human stem cell research findings into clinical practice for the unmet urgent medical need in treating SCI-resulted paralysis. If successful, it will provide optimal regeneration or reconstruction treatment options for the damaged or lost nerve tissue in both acute and chronic SCI patients that have been lacking, even lead to a dramatic functional improvement and recovery. The therapy development strategy of this project will bring the pluripotent hESC-based cell therapy from preclinical studies to market approval as a widely-accepted medical practice for spinal cord injury, a significant improvement in California’s patient care for SCI and integral to the goal of passage of Prop. 71. Clinical trials of the proposed novel hESC-based regenerative therapy for spinal cord repair first in California are an inevitable progress of California Stem Cell Initiative that will bring tremendous benefits to California’s economy and healthcare system. It will stimulate an emerging therapeutic market for hESC-based regenerative medicine, reduce disability costs, relieve health care and social welfare burden, and generate revenue for the state. The outcome of this project will have a transformative impact on improving the function, wellness, and overall quality of life for SCI patients, extending independent healthy life and reducing the burden of illness and disability.

© 2013 California Institute for Regenerative Medicine