hESC-Derived Motor Neuron Progenitors for the Treatment of Spinal Muscular Atrophy

Funding Type: 
Disease Team Research I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 
Our goal is to obtain FDA-approval for a stem cell-based therapy to treat the leading genetic killer of infants under 2 years of age, spinal muscular atrophy (SMA) Type I. SMA is a disease that first causes dysfunction of and then destroys motor neurons controlling all movement, including swallowing and breathing. There is no known treatment. The diagnosis of SMA Type I is usually made before 3 months of age and >95 percent die or require full-time respiratory support in infancy. Of all motor neuron diseases, SMA is the easiest to obtain FDA approval for, and presents the greatest clinical need given the certain death of afflicted infants. The information that we obtain will be directly relevant to SMA Type II and III, ALS, chronic spinal cord injury, and polio, all of which are characterized by motor neuron loss. The treatment involves transplantation of high-purity populations of human motor neuron cells derived from human embryonic stem cells (hESC-MNPs). We have already completed many steps towards FDA approval, including 1) production of a motor neuron manufacturing facility to make the cells in a manner compatible with human use, which has been audited and shown to be compliant with FDA guidelines for cell production, 2) small animal proof-of-concept studies which show that transplantation of our cells, made under FDA-compliant conditions, restores lost motor neurons in models of motor neuron loss, 3) FDA-reviewed safety studies which show that transplantation of our cells, made under FDA-compliant conditions, does not cause tumors, pain or any adverse events, and 4) multiple meetings with expert researchers and doctors resulting in a final clinical plan. Our team has been preparing for this clinical trial for 3 years, and has already held formal meetings with the FDA, so we do not require all 4 years of support. In this proposal, we are requesting 18 months of support for, 1) scale up of the cell manufacturing facility to prepare for the large volumes required for human treatment, and confirm that the scaled up production process produces the same quality cells as the current production process, 2) replication of small animal proof-of-concept studies which show that transplantation of our cells, made under FDA-compliant conditions, restores lost motor neurons in models of motor neuron loss, 3) large animal safety studies to test the accuracy of our cell delivery with available instrumentation, determine survival and differentiation rate of transplanted cells, and make sure that transplantation does not result in tumor formation or any adverse event, and 4) hire the staff to complete the pre-IND and IND filings.
Statement of Benefit to California: 
The treatment and care of individuals with motor neuron diseases represents a significant social and economic burden to the State of California. Specific to the first target indication, there are approximately 1,500 individuals affected by SMA currently living in the State of California and nearly 1,000,000 carriers of the SMA gene. Additionally, the Families of SMA Research Director, Dr. Jill Jarecki, is headquartered in San Diego. If successful, our clinical strategy will improve the function and quality of life of individuals with motor neuron diseases, which will lessen the cost that citizens and the State bear in terms of patient care. This program will position California for international competitiveness in this emerging area of biotechnology, as our clinical trial development strategy addresses critical barriers limiting the development of this sector in California and abroad. High purity cultures of hESC-derivatives enable transplantation approaches to disease, drug discovery, and predictive toxicology. This research plan will lead to the development and thorough characterization of a renewable source of human motor neurons that enables these 3 strategies as they pertain to spinal muscular atrophy, amyotrophic lateral sclerosis, polio, and spinal cord injury. Our program is within 18 months of being presented to the FDA for an IND. Thus, it will provide precedent in California for subsequent stem cell-based clinical trials, {REDACTED}. Thus, California will benefit from ‘hosting’ the discovery of what will become the first and second human embryonic stem cell-based clinical trials in the world. This will result in California being a focus of the stem cell industry, including large pharmaceutical companies that will eventually participate in the latter stage stem cell clinical trials. Clinically relevant scientific advances lead to the development of biotechnology companies, creating jobs and taxation. Funding for this proposal will directly create 11 new jobs. In these challenging economic times, we feel that any award should be spent in a manner which enhances the local and state economy, in essence returning direct value to the citizens of California. To this end, we have purposely selected suppliers of equipment and services that are located in the state of California. In addition, due to the booming medical device and biotechnology industries in California, we feel that all new hires can be obtained from within the state of California.

© 2013 California Institute for Regenerative Medicine