Cellular therapies, particularly those that use cord blood stem cells, have great potential to significantly advance the treatment of patients with acquired and genetic brain diseases. As it stands now, available treatments for neurological injuries are, unfortunately, , limited in scope. Most therapies are confined to supportive or palliative measures aimed at managing the symptoms of the conditions rather than the underlying causes. Recovery is, therefore, typically incomplete and often results in significant and permanent disabilities. These limitations have fueled research into possible treatments that could address the underlying causes rather than only the symptoms. There is tremendous interest—and strides are being made—in developing stem cell therapies as potential treatments to repair damage, regain function and improve quality of life in patients with neurological disorders. Such therapies represent a potential sea change in treatments and results.
Cord blood appears to hold promise as an effective therapy in neurological diseases, including genetic diseases of childhood, ischemic events such as stroke and neurodegenerative diseases of adulthood. Drs. Joanne Kurtzberg and Jessica M Sun from Duke University are the authors of a recent article, reviewing the potential use of umbilical cord blood as a source of stem cells for such therapies. Each of the conditions covered in their article have trials underway, illustrating the wide array of prevalent, devastating conditions that umbilical cord blood and cord tissue may be able to treat in the future.1
Cord Blood for Brain Injury: A Synopsis of the Latest Research
CHILDHOOD GENETIC BRAIN DISEASE
Children born with certain inherited metabolic diseases lack a critical enzyme necessary for the production and maintenance of myelin. The lack of myelin can result in progressive neurological deterioration. Affected babies may appear normal at birth but develop symptoms in the first months to years of life ultimately resulting in death in childhood. When patients with these diseases received a cord blood transplant early in the course of their disease, the cord blood stem cells were able to serve as a constant source of enzyme replacement. The natural progression of the disease was slowed or ceased—extending the patient’s life for decades—and neurologic functioning greatly improved.
Results suggest that the earlier in the disease course that the transplant is performed, the greater the benefit.2
Observations of cord blood used to treat children with genetic conditions led to the hypothesis that cord blood might also be beneficial in patients with brain injury. Infusion of cord blood cells in numerous animal models have demonstrated both neurological and survival benefits of cord blood cells in the setting of stroke, ischemia and intracranial hemorrhage.3
PERINATAL BRAIN INJURY
Repeated autologous cord blood infusions are being studied in young babies born with congenital hydrocephalus. In this condition, excessive accumulation of cerebral spinal fluid damages the developing brain leaving most children with many motor, sensory and cognitive deficits. At Duke University, more than 80 patients, ages 6 days to 4 years, have received autologous cord blood infusions for this condition. The results show that repeated dosing of autologous cord blood is safe even in very young babies and such a dosing scheme could be potentially advantageous for other neurologic conditions as well.
Phase I and II clinical trials have shown that an intravenous infusion of a child’s own cord blood cells, is safe and, when administered at a sufficient dose, leads to improvements in cognitive and select motor functions in children with cerebral palsy. Because many children with cerebral palsy do not have their own cord blood banked, trials are underway to find ways to safely use cord blood from siblings (when
available) or unrelated donors.4
The cause of autism is still the subject of much investigation. With stem cell therapy emerging as potential treatment for other neurological conditions, the question of whether it might have a role in the treatment of autism has also been raised. In a mouse model with autism, animals that received injections of human adipose-derived stem cells had decreased repetitive movements and improved social activity. This finding, in conjunction with early observations of increased brain connectivity in young children with cerebral palsy receiving autologous cord blood infusions, gives reason to believe that cord blood infusion may aid in the restoration of faulty neural connections in children with autism thereby improving the clinical symptoms.5 Clinical trials are underway at Duke University in North Carolina and the Sutter Institute in California using autologous cord blood treatment in children with autism.
In this class of diseases, a slow, progressive loss of a specific cell population is taking place. The neuroprotective therapies given early in the course of disease could potentially slow or halt disease progression. Stem cell therapies to treat neurodegenerative diseases have been studied most extensively in Parkinson’s disease, a disease defined by the degeneration primarily of nigrostriatal dopaminergic neurons. Interest therefore has grown in generating dopaminergic neurons from other cell sources. Studies indicate that cord blood is a potential source of stem cells for cellular replacement strategies in the treatment of Parkinson’s because of the prevalence of such neurons being derived from cord blood.6 Trials done with mice treated with cord blood mesenchymal stromal cells show decreased cognitive impairment and an extended lifespan in Alzheimer’s disease.7 ALS (also known as Lou Gehrig’s
Disease) is another condition that may be responsive to cellular therapy. Cord blood has been investigated in a mouse model of ALS and delayed the onset of the disease and extended survival by 20-25%. Cord blood stem cells were detected throughout the brain and spinal cord but concentrated in the anterior horn of the spinal cord, an area known to be affected by ALS.8
In the context of brain injuries, stem cell therapy may play both a neuroprotective role by dampening the inflammatory response, particularly in the acute setting, as well as a reconstructive role by enhancing the brain’s repair mechanisms. Such a therapy in adults would be truly revolutionary and have public health ramifications, given the high prevalence of these conditions. Because of its relative availability, favorable safety profile and pluripotential nature, cord blood is a prime source of stem cells for such therapies. Neurological injuries are typically associated with permanent and life-long disabilities, hefty expenses and a lack of therapeutic options. Until now, treatments, while providing relief from symptoms, have not been able to make a long-lasting impact on the root cause of such conditions. “Much work remains to be done in preclinical and clinical studies to further define efficacy, dose, route, timing and need for immunosuppression before cell-based therapies can be routinely used in the clinic. Nonetheless, cellular therapies particularly those that use cord blood stem cells, have great potential to significantly advance the treatment of patients with acquired and genetic brain diseases.”
1Kurtzberg, Joanne, Sun, Jessica M. Cord Blood for Brain Injury. Cytotherapy, International Society for Cellular Therapy, 24 February, 2015.
2Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, et al. Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. New England Journal of Medicine 220; 352:2069-81.
3Meier C, Middelanis J, Wasielewski B, Neuhoff S, Roth-Haerer A, Gantert M, et al. Spastic paresis after perinatal brain damage in rats with hemorrhagic brain damage in rats is reduced by human cord blood mononuclear cells. Pediatric Res 2006;59:244-9.
4Englander AZ, Pizoli CE, Batrachenko A, Sun J, Worley G, Mikati MA, et al. Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts. Neuroimage Clin 2013;2:440-7.
5Ha S-JL, S, Suh YH, Chang KA. Therapeutic effects of human adipose-derived stem cells in VPA-induced autism mouse model. Neuroscience. 2013. Poster 50.01/Q57.
6Xiong N, Zhang Z, Huang J, Chen C, Jia M, Xiong J, et al. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson’s disease. Gene Therapy 2011:18:394-402.
7Narlington D, Deng J, Giunta B, Hou H, Sanberg CD, Kuzmin-Nichols N, et al. Multiple low-dose infusions of human umbilical cord blood cells improve cognitive impairments and reduce amyloid-betaassociated neuropathology in Alzheimer mice. Stem Cells Dev 2013;22:412-21.
8Garbuzova-Davis S, Rodrigues MC, Mirtyl S, Turner S, Mitha S, Sodhi J, et al. Multiple intravenous administrations of human umbilical cord blood cells benefit in a mouse model of ALS. PLoS One.