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New Medical Research Focused on Cord Blood Stem Cells to Help Treat Brain Injury

A ground-breaking clinical trial underway at The University of Texas Health Science Center at Houston (UTHealth) is an innovative step in a growing number of studies exploring the potential of stem cell-based therapies to help initiate repair and induce healing of damaged brain tissue. The study is being performed in partnership with Children’s Memorial Hermann Hospital, UTHealth’s major children’s teaching hospital.

The trial will involve children who have sustained traumatic brain injuries and who have access to their own umbilical cord blood stem cells, which were banked at birth. Children who meet the trial qualifications will travel to Children’s Memorial Hermann Hospital to receive an IV infusion of their cord blood stem cells. They will then be followed at six months, one year and two years.

“The reason we have become interested in cord blood cells is because of the possibility of autologous therapy, meaning using your own cells. And the preclinical models have demonstrated some really fascinating neurological preservation effects to really support these Phase 1 trials,” says Charles S. Cox, M.D., Children’s Fund Distinguished Professor of Pediatric Surgery and Pediatrics at the UTHealth Medical School, director of the Pediatric Trauma Program at Children’s Memorial Hermann Hosptial, and principle investigator of the trial. “There’s anecdotal experience in other types of neurological injuries that reassures us in terms of the safety of the approach and there are some anecdotal hints at it being beneficial in certain types of brain injury.”

The Phase I safety study will enroll 10 children ages 18 months to 17 years who have suffered moderate to severe traumatic brain injury (TBI) and are within 6 to 18 months of their injury.

A Closer Look at Brain Injuries

Brain injuries result from numerous causes including traumatic injuries from a physical force or non-traumatic injures such as a lack of blood supply to the brain. Most brain injuries fall into one of three categories:

• Traumatic Brain Injury (TBI): occurs when a sudden trauma causes damage to the brain,
   such as the head colliding with an object or an object piercing the skull and damaging the
   brain tissue.(1)

• Non-Traumatic or Acquired Brain Injury: is damage to the brain resulting from insults such
   as a lack of oxygen, glucose or blood to the brain or exposure to a toxin. With a non-traumatic
   injury, damage is usually spread throughout the brain, whereas TBI may be localized to one
   area.(2)

• Perinatal Brain Injury: a non-traumatic brain injury sustained during the perinatal period which is typically defined as the five months prior to birth through one month after birth. These brain injuries may result from lack of oxygen or blood to the brain, perinatal stroke, infection, brain malformation, genetic disorders and many other conditions. Infants may develop permanent neurological impairment such cerebral palsy, epilepsy, learning disabilities or behavioral disorders.(3,4)

 Current Protocol for Brain Injury Cases

Today there is no therapy that can repair damage to the brain tissue. Current protocol focuses first on stabilizing the individual in order to minimize the damage and prevent further injury and second, on managing symptoms of the injury. Moderately to severely injured patients receive rehabilitation treatment tailored to the individual’s neurological impairment in areas such as physical therapy, occupational therapy, speech/language therapy, psychology, psychiatry, and social support.(1)

Therapies Under Research – Cord Blood Stem Cell Infusions

Cord blood is one source of stem cells that has shown promise in preclinical research and is now being explored in experimental treatments for patients with brain injury. In the preclinical or lab setting, research has shown that cord blood stem cells have the ability to divide and change into neural-like cells.(5,6) Additionally, these stem cells have been shown to migrate to the area of injury, and to secrete therapeutic factors, which may help repair brain damage.(7,8,9). Further preliminary findings from studies underway at UTHealth indicate that cord blood stem cells may also alter the body’s immune response to injury, by interacting directly with the organs and cells of the immune system that enable the body to better repair itself.(10)

Here is an overview of the human clinical studies at leading research institutions across the country that are already underway:

UTHealth – As a pre-cursor to the clinical trial on cord blood stem cells, a recently completed Phase 1 study at UTHealth investigated autologous (one’s own) bone marrow stem cell therapy in children with acute traumatic brain injury and revealed positive safety results.(11)

UTHealth is also investigating autologous stem cell therapy for acute stroke patients in an NIH-sponsored Phase 1 study by Sean Savitz, M.D., associate professor in the Department of Neurology; and for acute myocardial infarction (heart attack) patients in a Phase 2 study led by Ali E. Denktas, M.D., assistant professor in the Department of Internal Medicine.(12,13)

Duke University – Researchers at Duke University are conducting a clinical trial testing the safety and feasibility of infusing autologous (one’s own) cord blood in infants with signs of a brain injury caused by hypoxia (lack of oxygen). The researchers will evaluate the effect of the cord blood infusion on neurodevelopmental function and neuroimaging results compared to historic controls.(14)

A separate clinical trial at Duke is examining the efficacy of a single intravenous infusion of autologous cord blood for the treatment of pediatric patients with spastic cerebral palsy. The primary measure of efficacy will be improvement of standardized measures of neurodevelopmental function.(15)

Early investigational work studying autologous cord blood infusions in more than 200 children with various forms of brain injury was pioneered at Duke University. Although not formally measured, parents of infants who underwent the experimental cord blood stem cell infusions for cerebral palsy have reported subjective improvements in their children after the procedure.

Georgia Health Sciences University – Researchers here are conducting the first FDA-approved clinical trial evaluating the use of a child’s own cord blood stem cells as a medical intervention for cerebral palsy. The study will include 40 children, ages 1 to 12. Children will begin the study with a neurological exam. Then, half of the study participants will receive an infusion of their own cord blood while the other half receives a placebo. Three months later, the children will be evaluated without physicians knowing which group received the stem cell infusion. Afterward, children who didn’t get the cord blood initially will receive an infusion. Children in the study will return three and six months later for evaluation, where researchers will assess their motor skills and neurological development.(16)

“Stem cell research holds great promise for the 1.7 million children and adults in the U.S. who sustain traumatic brain injuries each year,” according to Susan Connors, president and chief executive officer of the Brain Injury Association of America. “We welcome investigations into this growing population and eagerly await favorable results.”

1. National Institute of Neurological Disorder and Stroke. NINDS Traumatic Brain Injury Information Page. Available at http://www.ninds.nih.gov/disorders/tbi/tbi.htm. Accessed July 31, 2008.
2. Brain Injury Association of America. Living with Brain Injury – Education. Available at http://www.biausa.org/education.htm#causes. Accessed October 2010.
3. Adamson SJ, Alessandri LM, Badawi N, Burton PR, Pemberton PJ, Stanley F. Predictors of neonatal encephalopathy in full-term infants. BMJ. 1995;311(7005):598-602.
4. Ferriero DM. Neonatal brain injury. N Engl J Med. Nov 4 2004;351(19):1985-1995.
5. McGuckin CP, Forraz N, Allouard Q, Pettengell R. Umbilical cord blood stem cells can expand hematopoietic and neuroglial progenitors in vitro. Exp Cell Res. May 1 2004;295(2):350-359.
6. Lee MW, Moon YJ, Yang MS, et al. Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2007;358(2):637-643.
7. Hau S, Reich DM, Scholz M, et al. Evidence for neuroprotective properties of human umbilical cord blood cells after neuronal hypoxia in vitro. BMC Neurosci. 2008;9:30.
8. Neuhoff S, Moers J, Rieks M, et al. Proliferation, differentiation, and cytokine secretion of human umbilical cord blood-derived mononuclear cells in vitro. Exp Hematol. l 2007;35(7):1119-1131.
9. Pimentel-Coelho PM, Magalhaes ES, Lopes LM, deAzevedo LC, Santiago MF, Mendez-Otero R. Human cord blood transplantation in a neonatal rat model of hypoxic-ischemic brain damage: functional outcome related to neuroprotection in the striatum. Stem Cells Dev. 2010r;19(3):351-358.
10. Personal communication: James Baumgartner, M.D., pediatric neurosurgeon at Children’s Memorial Hermann Hospital.
11. Cox CS, Jr., Baumgartner JE, Harting MT, et al. Autologous Bone Marrow Mononuclear Cell Therapy for Severe Traumatic Brain Injury in Children. Neurosurgery. Dec 16.2010. [Epub ahead of print]
12. ClinicalTrials.gov. Safety/Feasibility of autologous mononuclear bone marrow cells in stroke patients. Available at http://www.clinicaltrials.gov/ct2/show/NCT00859014?term=bone+marrow+and+acute+stroke+and+Texas&rank=1. Accessed October 2010.
13. ClinicalTrial.gov. Use of adult autologous stem cells in treating people who have had a heart attack. Available at http://www.clinicaltrials.gov/ct2/show/NCT00684021?term=bone+marrow+and+phase+2+and+myocardial+infarction+and+Texas&rank=1. Accessed October 2010.
14. ClincialTrials.gov.Cord blood for neonatal hypoxic-ischemic encephalopathy. Available at http://www.clinicaltrials.gov/ct2/show/NCT00593242?term=cord+blood+and+Duke&rank=1. Accessed October 2010.
15. ClinicalTrials.gov. A randomized study of autologous umbilical cord blood reinfusion in children with cerebral palsy. Available at http://www.clinicaltrials.gov/ct2/show/NCT01147653?term=cord+blood+and+Duke&rank=3. Accessed October 2010.
16. ClinicalTrials.gov. Safety and effectiveness of cord blood stem cell infusion for the treatment of cerebral palsy in children. Available at http://www.clinicaltrials.gov/ct2/show/NCT01072370?term=cord+blood+and+cerebral+palsy+and+medical+college+of+georgia&rank=1. Accessed October 2010.

About the Author

The CBR Center for Regenerative Medicine helps advance medical research being conducted by leading physicians and medical institutions who are exploring the potential of newborn stem cells through regenerative medicine research and FDA-regulated clinical trials.

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