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Neurological


Dr. Sarah Busch gives an overview of the exciting preclinical research being conducted by Athersys and collaborators around the world using MultiStem®.

Video Chapters
0:00 Introduction
2:35 Hemorrhagic Stroke
8:50 Traumatic Brain Injury
9:22 Spinal Cord Injury
9:48 Multiple Sclerosis
10:46 Organ Transplant (kidney)
13:33 Adoptive T-regulatory cell therapy

Another focus of our regenerative medicine program is MultiStem administration for the treatment of neurological injury as a result of acute or chronic conditions. Neurological injury and disease represent an area of significant unmet medical need, a major burden on the healthcare system, and also represents a huge commercial opportunity.

Many neurological conditions require extensive long-term rehabilitative therapy, and many require extended hospitalization and/or institutional care, creating an enormous quality of life and cost burden. Stroke represents an area where the clinical need is particularly significant, since it represents a leading cause of death and significant long-term disability. We have published research with independent collaborating investigators that demonstrates that MultiStem administration conveys biological benefits in preclinical models of both ischemic and hemorrhagic strokes, as well as other models of neurological damage and injury, including TBI, neonatal hypoxic ischemia (a cause of neurological damage in infants), and spinal cord injury. We also conducted preclinical work in other neurological areas and have been awarded grants from time-to-time in support of this work, including the potential of MultiStem cells to address chronic conditions such as multiple sclerosis (MS) or Parkinson’s disease. Our research has shown that MultiStem cells convey benefits through distinct mechanisms, including reducing inflammatory damage, protecting at risk tissue at the site of injury, and through direct neurotrophic effects that stimulate the recovery of damaged neurons. As a result, we believe that MultiStem therapy may have relevance to many forms of neurological injury and disease.

Our initial clinical focus in the neurological area involves evaluating MultiStem administration to treat ischemic stroke, which is now in Phase 3 of clinical development. Please visit our Stroke page to learn more.

Traumatic Brain Injury (TBI)

We are also interested in the application of MultiStem for other neurological indications that represent areas of significant unmet medical need, such as TBI, which represents the leading cause of disability among children and young adults, and a leading cause of death. In preclinical studies of TBI, administration of MultiStem dramatically reduced the extent of damage caused by a TBI and promoted accelerated healing of the blood-brain barrier. With grant funding from the NIH, we advanced our MultiStem programs and cell therapy platform, including development of MultiStem therapy for the treatment of TBI and further development of our cell therapy formulations and manufacturing capabilities.

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MAPC (green) transplanted into the injured rat spinal cord prevent axons (red) from retracting and promote regrowth in the presence of macrophages and microglia (purple).

Source: Multipotent Adult Progenitor Cells Prevent Macrophage-Mediated Axonal Dieback and Promote Regrowth after Spinal Cord Injury
Sarah A. Busch, et. al. Journal of Neuroscience 19 January 2011, 31 (3) 944-953.

Spinal Cord Injury

We are also conducting preclinical work exploring the application of MultiStem treatment in other acute neurological indications. Through publications and presentations, Athersys and our collaborators have demonstrated that intravenous MultiStem administration one day after spinal cord injury, or SCI, results in statistically significant and sustained improvements in gross locomotor function, fine locomotor function and bladder control compared to SCI animals who did not receive cells. Intravenous administration of our cells one day after injury prevented loss of spinal cord tissue, resulting in significant improvement of walking function and urinary control. Further, we have published articles demonstrating evidence that our cell therapy has the potential to provide benefit following hypoxic ischemia, an injury caused by oxygen deprivation to the brain before or during birth and represents a leading cause of cerebral palsy. These findings are consistent with previous findings in related areas, such as ischemic stroke, and add to the scientific foundation supporting MultiStem cell therapy for the treatment of acute neurological injuries.

Multiple Sclerosis

With funding support from National Multiple Sclerosis Society through Fast Forward, we have investigated the potential for MultiStem treatment for chronic progressive multiple sclerosis (MS). MS is a disease of the central nervous system (CNS) in which infiltration of immune cells leads to demyelination and axonal loss, disrupting the flow of information between the brain and the body. Using several preclinical models of MS, researchers observed that MultiStem cell administration arrests the demyelination process and supports remyelination of affected axons, resulting in sustained behavioral improvements. We next investigated the mechanism of action underlying the enhanced remyelination in the presence of MultiStem cells. We found that MultiStem cell secreted factors increase the generation of oligodendrocytes, the myelin producing cells within the CNS which provide support and insulation to axons. Together, these findings demonstrate the potential benefits of MultiStem therapy for treating MS.

MultiStem-conditioned media drives new oligodendrocyte formation and remyelination in a multiple sclerosis model (Top photo – control):
Oligodendrocytes (green) grown without conditioned media. (Bottom photo) Oligodendrocytes grown in the presence of MultiStem conditioned media. New oligodendrocyte formation is visible, supporting our work in multiple sclerosis.

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