Families of Spinal Muscular Atrophy Funded Stem Cell Motor Neuron Replacement Program.
December 30, 2008.
FSMA has invested significant resources in alternative approaches that show promise to cure Spinal Muscular Atrophy rather than just treat the symptoms. In particular, we have invested $1.5 Million to develop a motor neuron replacement therapy for SMA, and we have made significant progress with our investment.
Our initial investment in stem cell research in 2000 funded efficacy studies using motor neurons from mouse stem cells. Results show that this therapy can provide benefit to rodents with motor neuron disease: a highly significant finding. In 2005, additional FSMA funding lead to the first, highly-pure therapeutic population of human motor neurons for cellular replacement therapy for SMA. This program is now progressing on the path to IND in collaboration with the biotech firm California Stem Cell, Inc. (CSC), and leading research centers at University of California-Irvine, and Johns Hopkins University. These motor neurons recently completed a series of critical animal safety studies prior to advancing into human trials for SMA.
Motor neuron replacement is at the leading forefront of current scientific knowledge, and as such is very high risk. However, this approach allows for the possibility of replacing lost motor neurons and so holds great promise for the patients and families in our community.
“FSMA provided the first financial support for my research program investigating the development of high purity human motor neuron populations from stem cells, and their application to animal models of SMA. This work has grown into a multi-tiered program that now involves several funding agencies, an industry collaborator, a clinical collaborator and FDA relations. I will always consider FSMA my partner in pioneering this technology, and moving it towards human use.” Hans S. Keirstead, Ph.D., Associate Professor of Anatomy and Neurobiology, Co-Director of the Sue and Bill Gross Stem Cell Research Center, University of California at Irvine.
Pre-clinical efficacy studies have been completed, demonstrating correct localization of CSC motor neurons in the ventral spinal cord, cell growth from the spinal cord toward the limbs, synapse formation with target muscle and functional reinnervation leading to restoration of limb function in animal models of motor neuron loss.
Results of the Safety Study for SMA Type I Clinical Application:The pivotal safety study, required to support an application to begin FDA clinical trials, has recently been completed. Although final data analysis is still in progress, there were no negative outcomes of this study, leading to the conclusion that motor neuron replacement will be a safe strategy in the treatment of diseases such as SMA characterized by motor neuron loss.
The purposes of this study were to evaluate the capacity of a motor neuron progenitor cell population to form tumors following transplantation into the spinal cord, to determine whether motor neuron transplantation would induce allodynia (increased pain sensitivity), and to evaluate the biodistribution and potential toxicity of motor neurons transplanted into the spinal cord. Results showed:-No mortality attributed to treatment with motor neuron progenitors occurred.-No tumors occurred that were attributed with the transplanted motor neurons.-No statistically significant differences occurred between the cell buffer (control) and treatment groups in the clinical allodynia (pain) assessments.-No toxicological profile differences between control and treatment groups.-No gross or histologic findings were attributed to the transplantation of CSC motor neurons.
Preparations for Clinical Trial Approval:“California Stem Cell has developed methods for the manufacture of clinical grade human motor neurons. It is the intent of CSC to gain approval to begin FDA-approved clinical trials for the use of these cells in development of a cell replacement therapy for SMA Type I. CSC is now preparing for a final FDA pre-IND meeting to take place in the first quarter of 2009, keeping us on track for a formal application in the second quarter of 2009 to begin a Phase I/IIA clinical trial in SMA Type 1.” Chris N Airriess, Ph.D., Chief Operating Officer, California Stem Cell, Inc.
Other preparations currently underway include: An external clinical trials coordinator has been engaged and medical community focus groups held to develop the clinical strategy for SMA trials; CSC manufacturing facilities and procedures have been audited for compliance with guidelines for clinical manufacturing.
