Stem Cells Inc. Reports Positive Safety Data in Their Spinal Cord Injury Trial With Human Neural Stem Cells

StemCells, Inc., a biotechnology company based in Newark, California, has reported the results of their initial safety review of their human purified neural stem cell line implantations. This report represents the first planned interim safety review of the Company’s Phase I/II spinal cord injury clinical trial. This clinical trial involved a surgical implantation of the stem cells, and suppression of the immune system with anti-rejection drugs. The results of the safety trial show that both parts of the procedures seem to be well tolerated.

This trial was designed to determine the safety and potential, efficacy of the StemCells, Inc. proprietary HuCNS-SC® cells in spinal cord injury patients. HuCNS-SC cells are a purified human neural stem cell line that can form all the cells of the central nervous system (Taupin P. Curr Opin Mol Ther. 2006;8(2):156-63). When these cells are implanted into the retinas for rats that are suffering from retinal degeneration, they form a variety of retinal-specific cell types and seem to aid in retinal regeneration (McGill TJ., et al., Eur J Neurosci. 2012;35(3):468-77).

This clinical trial represents the first time that human neural stem cells have been implanted into the spinal cords of human patients as a potential therapeutic agent for spinal cord injury. The interim data come from the first cohort of patients. All of these first cohort patients suffered a complete spinal cord injury, and show no neurological function below the level of the injury.

All patients in the trial were transplanted with 20 million neural stem cells at the site of injury in the thoracic spinal cord. Observation of the patients revealed that there were no detectable abnormal responses to the cells, and all the patients were neurologically stable through the first four months following transplantation of the cells. Changes in sensitivity to touch were observed in two of the patients. These data merit the continuance of the trial, and further enrollments. Patients with partial spinal cord injuries, who might experience a broader range of improvements are also being sought for enrollment.

Armin Curt, M.D., principal investigator for the clinical trial, said, “We are very encouraged by the interim safety outcomes for the first cohort.”  Dr. Curt is Professor and Chairman of the Spinal Cord Injury Center at the University of Zurich, and Medical Director of the Paraplegic Center at Balgrist University Hospital. Dr. Curt continued, “The patients in the trial are being closely monitored and undergo frequent clinical examinations, radiological assessments by MRI and sophisticated electrophysiology testing of spinal cord function. The comprehensive battery of tests provides important safety data and is very reassuring as we progress to the next stage of the trial.”

Muscle Cells Made from Induced Pluripotent Stem Cells Successfully Treat Mice With Muscular Dystrophy

Work by researchers at the Lillehei Heart Institute at the University of Minnesota have demonstrated the ability of induced pluripotent stem cells (iPSCs) to make muscle-forming cells, and that these cells can be used to treat muscular dystrophy.

Muscular dystrophy refers to a group of inherited diseases that causes muscle fibers to be structurally weak and highly susceptible to damage. The progressive muscle damage causes the muscles to become gradually weaker and weaker until the patient will eventually require a wheelchair.

There are several different types of muscular dystrophy. Most of the varieties of muscular dystrophy causes symptoms appear during childhood, but others cause symptoms to arise during adulthood. The most common form of muscular dystrophy is Duchenne muscular dystrophy (DMD). The symptoms begin early in life (once the child learns to walk), and include frequent falls, difficulty getting up from a lying or sitting position, trouble running and jumping, waddling gait, large calf muscles, and learning disabilities. A less severe and slower progressing form of muscular dystrophy is Becker muscular dystrophy (BMD). Symptoms usually being in the teenage years, but might also not occur until the mid-20s or later. Other types of muscular dystrophy include myotonic (inability to relax muscles at will, most often begins in early adulthood, muscles of the face are usually the first to be affected), Limb-girdle (hip and shoulder muscles are first affected), congenital (apparent at birth or becomes evident before age 2 and varies in severity), fascioscapulohumeral (shoulder blades stick out like wings when the person raises his or her arms, onset occurs in teens or young adults), and oculopharyngeal (drooping of the eyelids and weakness of the muscles of the eye, face and throat, symptoms first appear in a person’s 40s or 50s).

In order to treat muscular dystrophy (MD), many researchers have tried to use gene therapy to place normal versions of the muscular dystrophy gene (which encodes a protein called Dystrophin) into the muscles of MD patients (Romero NB, et al., Hum Gene Ther. 2004;15(11):1065-76 & Mendell JR, et al., Ann Neurol. 2009;66(3):290-7. These types of experiments have met with limited success, since the immune system of muscular dystrophy patients tends to attack the muscles that express dystrophin (Mendell JR, et al., New England Journal of Medicine 2010 7;363(15):1429-37).

In light of the failure of gene therapy trials, researchers have tried stem cell treatments in MD mice. Scientists in the laboratory of Rita Perlingeiro have used muscle precursor cells made from mouse embryonic stem cells to treat MD mice (Radbod Darabi, et al., Exp Neurol. 2009; 220(1): 212–216). Given this early success, Perlingeiro and her co-workers have used mouse iPSCs to make muscle-forming cells that have been used to treat muscular dystrophy in MD mice. In this experiment, suppression of the immune system was not necessary, since the muscle cells were made from cells that came from the patients.

Perlingeiro said of the experiment, “One of the biggest barriers to the development of cell-based therapies for neuromuscular disorders like muscular dystrophy has been obtaining sufficient muscle progenitor cells to produce a therapeutically effective response. Up until now, deriving engraftable skeletal muscle stem cells from human pluripotent stem cells hasn’t been possible. Our results demonstrate that it is indeed possible and sets the stage for the development of a clinically meaningful treatment approach.”

Once transplanted, the muscle-forming cells (myogenic progenitor cells to be exact) moved into the damaged muscles and integrated into them. They formed skeletal muscle and provided extensive and long-term muscle regeneration that resulted in improved muscle function. To make the iPSC cell lines, Perlingeiro and her laboratory workers genetically modified to human iPSC lines with a gene called PAX7. PAX7 encodes a transcription factor that is essential for muscle formation and muscle regeneration. PAX7, with PAX3, designates cells as myogenic progenitor cells. Therefore, inserting the PAX7 gene into iPSCs would drive them to become myogenic progenitor cells.

Once Perlingeiro’s lab perfected the protocol for making myogenic progenitor cells from iPSCs, they found that they could make buckets and buckets of them. The iPSC-derived muscle forming cells were much more efficient at integrating into the muscles and regenerating them than other cell types. Muscle-forming stem cells from human muscle biopsies, for example, failed to persist in the muscle.

Perlingeiro concluded, “Seeing long-term maintenance of these cells without major side effects is exciting. Our research proves that these differentiated stem cells have real staying power in the fight against muscular dystrophy.”