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Making progress with MAPC
CLEVELAND—Athersys Inc. recently shared the results of a study of its MultiStem cell therapy, which is currently in clinical development. The company found that multipotent adult progenitor cells (MAPC), used in its cell therapy, are effective at improving the health of animals in the wake of acute rodent spinal cord injury, specifically with regards to the criteria of walking function and bladder control. The results of the study were published in Scientific Reports by Nature.
Athersys and Case Western Reserve University School of Medicine, led by Dr. Jerry Silver of the Department of Neurosciences, have been working together for a decade, with this study as the latest installment of their work together.
“Spinal cord injury continues to devastate the lives of many. Although a great deal of research needs to be undertaken in the field, we are pleased to see that MultiStem therapy is efficacious in promoting the recovery of locomotor and urinary functions in rodents. I am especially excited with this therapy as it circumvents the need for directed therapeutic delivery into the vulnerable, recently injured spinal cord. We look forward to working with Athersys and other leaders in the science community to fill this critical treatment gap,” Silver remarked in a statement.
The MultiStem therapy “consists of a special class of human stem cells that have the ability to express a range of therapeutically relevant proteins and other factors, as well as form multiple cell types. … These cells exhibit a drug-like profile in that they act primarily through the production of multiple factors that regulate the immune system, protect damaged or injured cells, promote tissue repair and healing, and the cells are subsequently cleared from the body over time.” Athersys notes on its website that MultiStem administration has been shown in preclinical studies to reduce inflammatory-mediated damage and enhance tissue repair and healing in models of neurological injury.
Nervous system injuries such as stroke, traumatic brain injury and spinal cord injury all result in excessive inflammation, which in turn is toxic to surrounding healthy tissue, making modulation of the immune system a leading therapeutic target for neurological injury. This study administered a single dose of MAPC to rodents a day after severe spinal cord injury, and the animals that received treatment showed significantly improved voluntary control of bladder function, walking ability and preservation of at-risk nervous tissue. The study also clarified a key mechanism of action of MAPC treatment, which functions through the modulation of neuro-inflammation and a significant reduction of inflammatory cell accumulation within the injury.
The team tracked the distribution of MAPC cells within the body post-injury, and found that a large number of them gathered in the spleen, a primary reservoir for inflammatory cells in the body. This result matched other evidence suggesting that a primary effect of the cell therapy takes place through modulation of systemic inflammation via splenic interactions. In addition, close examination of the spinal cord injury site, peripheral blood and the spleen revealed noticeable changes in inflammatory pathways following MAPC administration.
“The results described in this important publication build on and are consistent with previously completed preclinical and clinical studies in acute neurological injuries, including the Phase 2 study in ischemic stroke,” Dr. Robert Mays, senior vice president and head of Neurosciences at Athersys, said in a press release. “The data show consistent mechanisms of action for MultiStem in targeting and modulating the immune system, and enhancing recovery and repair. Importantly, these results support our belief that the intravenous administration of MultiStem may lead to durable and substantial benefits in humans, which is consistent with our clinical observations in other programs. Athersys commends the outstanding work of Jerry Silver’s lab at Case Western Reserve University School of Medicine, and we look forward to additional progress that will enable the clinical translation of this therapy for spinal cord injured patients.”
Donna Sullivan, project director for Unite 2 Fight Paralysis, added, “We are excited by these results in rodent models of spinal cord injury, which demonstrate that MultiStem therapy may have the potential to enhance patients’ lives by improving critical locomotor and bladder functions. Improvement in these functions will reduce the many life threatening secondary conditions, which are a result of the loss of these functions. Unite 2 Fight Paralysis looks forward to additional opportunities to partner with this team of scientists to bring this cell therapy to the bedside.”
Dr. Sarah Busch and other Athersys scientists coordinated this research in collaboration with Silver, graduate student Marc DePaul and other scientists from Case Western Reserve University School of Medicine, with grant support from The Ohio Third Frontier.