StemCells, Inc., the California company that has already begun clinical trials in Switzerland for its human neural stem cell line (HuCNS-SC ) in thoracic spinal cord injury, was awarded $20 million yesterday to fund preclinical animal studies of the company’s cells as a potential treatment for cervical spinal cord injury.
The money comes from the California Institute for Regenerative Medicine (CIRM) as part of its Disease Team Therapy Development Award program. A total of $150 million was funded, including projects in Huntington’s disease, heart disease and cancer. Here’s the CIRM press
release.
The SCI award will be directed by
Aileen Anderson and her team, including husband Brian Cummings, at the Reeve-Irvine center at the University of California, Irvine. Anderson, who also did the animal studies for the Swiss StemCells trial, has a long relationship with the Reeve Foundation. She began her career studying Alzheimer’s disease but was recruited to become an Associate in the Reeve International Research Consortium on Spinal Cord Injury in the Carl Cotman lab at UCI.
Now, as well as running her own full-fledged lab, Anderson is also scientific director of the Foundation’s Injury Core Laboratory at UCI – a custom lab of sorts for ra custom lab of sorts for use by the Foundation's Research Consortium.
The CIRM funds cover a maximum four-year period, with the goal of filing an investigational new drug (IND) application to begin human trials in 2015.
StemCells, Inc. predicted that California would realize $3 billion in savings if a treatment could modestly improve function of one or two cervical levels in 3.5 percent of quads. The pharamacoeconomics go like this:
Converting a tetraplegic to a paraplegic could save $770,000 over the lifetime of 1 patient. Thus, an effective stem cell therapeutic has the potential to not only significantly impact individual quality of life and independence of SCI patients, but would also reduce the shared costs of health care and loss of productive employment. Extrapolating these savings to just the estimated 77,000 cervical patients in California results in an estimated $86 billion dollars in reduced health care costs, assuming every patient was eligible for treatment and responded positively. If only 3.5% of this potential were realized, this one HuCNS-SC treatment indication could save California $3 billion dollars.
Here are some details from the newly funded SCI project, from the company’s application to CIRM:
Neural stem cells are capable of differentiation to neurons, oligodendrocytes, and astrocytes following transplantation into the intact, diseased, or injured central nervous system (CNS). Hence, neural stem cell strategies that have the potential to contribute to both bridge circuitry and remyelination may provide synergistic benefits.
….We have previously shown that human CNS-derived Neural Stem Cells (HuCNS-SC) transplanted into the injured thoracic spinal cord are capable of extensive migration, and exhibit predominant differentiation to oligodendrocytic and neuronal phenotypes, with the capacity for myelination of, and synapse formation with, host axons.
… These data suggest that HuCNS-SC remain capable of migration within the inhibitory microenvironment of the injured spinal cord, an unusual characteristic that may increase the potential for these cells to functionally integrate within the host CNS to mediate repair.
Here is a summary of the data from Anderson’s studies for StemCells, Inc.:
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Reproducible locomotor recovery was observed in thoracic SCI after sub-acute and chronic SCI HuCNSSC transplantation. No functional recovery was observed when HuCNS-SC cells were transplanted immediately post-SCI, indicating timing of intervention is critical, with delayed better than immediate.
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HuCNS-SC cells retain multipotency and migrate extensively within the injured spinal cord, with evidence of predominant oligodendrocytes differentiation, as well as HuCNS-SC remyelination of, and synapse formation with, host processes.
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No evidence of increased mechanical allodynia/hyperalgesia in any tested SCI transplantation paradigm. No tumor formation, abnormal cellularity, or evidence of contribution to glial scar formation in animals receiving HuCNS-SC.
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Locomotor recovery was observed in a proof-of concept sub-acute cervical SCI model, with predominant HuCNS-SC oligodendrocyte lineage differentiation.
Interestingly, the animal model timing of 9 days and 60 days post injury translates in humans to three to 24 months – truly addressing the chronic SCI population.
Why not embryonic cells? From the application:
While embryonic stem cells (ESC) are widely considered to possess the greatest flexibility and capacity for application to neurological diseases, they also have the greatest potential for uncontrolled division and hence the greatest risk of tumor formation. An alternative strategy is to generate tissue-derived expandable stem cell lines that are neural committed. …HuCNS-SC are derived from human fetal brain obtained from consenting donors in compliance with state and federal laws and regulations governing the procurement of human tissue.
What about dosage? Geron used a clinical cell dose of two million cells, identical to the dose tested in their animal safety/toxicology studies. StemCells, in its Swiss study, injects 20-60 million cells into human cords.
What determines trial success? First, no tumors or “aberrant morphology” in tested animals. Second, there has to be functional recovery. Efficacy for cervical models is different that for thoracic, which measures open-field hind limb function. The new study considers success as a 25 percent reduction in errors as animals cross a ladderbeam, and a 50 percent increase in coordinated stepping.
