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Novel Drug Delivery Systems to Treat Mild Traumatic Brain Injury Based on Carbon Nanotubes

Published on August 23, 2008 at 10:12 AM

Of the more than 1.5 million people who suffer a traumatic brain injury each year in the United States, as many as 75 percent sustain a concussion, a brain injury that is classified as mild yet can lead to long-term or permanent impairments and disabilities. A consortium of physicians and scientists in the Houston region is now undertaking a research initiative to improve diagnosis of mild traumatic brain injury (MTBI) and develop innovative treatment strategies.

The Department of Defense Post-Traumatic Stress Disorder and Traumatic Brain Injury Research Program of the Office of Congressionally Directed Medical Research Programs recently awarded the Mission Connect Mild TBI Translational Research Consortium a grant totaling approximately $35 million to support the five-year research program. The consortium includes research teams from The University of Texas Health Science Center at Houston, The University of Texas Medical Branch at Galveston (UTMB), Baylor College of Medicine, Rice University and the Transitional Learning Center in Galveston. The work will be done within the existing framework of Mission Connect, a consortium established by the TIRR Foundation in 1997 to facilitate collaborative research to improve outcomes for patients with brain and spinal cord injuries and neurological disorders.

"Our goal is to make discoveries that will ultimately allow us to intervene with the most effective early therapy before a mild traumatic brain injury results in a chronic problem," said Alex Valadka, M.D., the consortium's principal investigator, vice chairman of the Department of Neurosurgery at The University of Texas Medical School at Houston and director of neurotrauma services at Memorial Hermann - Texas Medical Center (TMC). "There is a high prevalence of mild traumatic brain injury in soldiers, and the consortium's work is driven by that. We believe the conclusions of our research also will benefit civilians, including athletes, who have suffered concussions."

The consortium's members will collaborate on basic and clinical research to develop new diagnostic methods, including sophisticated imaging techniques, and evaluate new therapeutic interventions. For clinical trials, the researchers plan to recruit patients with mild TBI who are receiving care at Memorial Hermann -TMC, Ben Taub General Hospital and Michael E. DeBakey VA Medical Center. "The award of this grant confirms the collaborative platform of Mission Connect is a powerful and pivotal force in research," said Cynthia Adkins, executive director of TIRR Foundation, under which Mission Connect was founded and is managed. "Uniting these premier scientists in this shared research effort will accelerate the pace of discovery and provide the courageous men and women in our military with the best possible medical care for the brain injuries they have sustained."

Claudia Robertson, M.D., professor of neurosurgery at Baylor College of Medicine and director of The Center for Neurosurgical Intensive Care at Ben Taub General Hospital, is the co-principal investigator. "This grant is a huge boost to research in traumatic brain injury and will allow investigators to work together through Mission Connect," she said. "For Baylor College of Medicine, it will help fund 10 investigators in neurology, neuroscience, neurosurgery and pain management and physical rehabilitation."

Claire Hulsebosch, Ph.D., professor of neuroscience and cell biology at UTMB, said Mission Connect is unique in that it provides a multi-institutional forum for collaborative research, and not an outdated model of competition among medical researchers.

"Only through collaboration can we make great strides in restoring function for our young, brave men and women in the armed forces," Hulsebosch said. "We in the medical field must serve these men and women by moving the frontiers of treatment faster to provide state-of-the-art interventions now.

"An effort led by Drs. Doug DeWitt and Donald Prough of the Moody Center for Brain and Spinal Cord Injury/Mission Connect at UTMB is a pivotal component of the Department of Defense project, leading the field with a new blast injury model that simulates the exposure to improvised explosive devices. Additionally, innovative therapies using stem cells, anti-inflammatory agents, growth hormones and the expertise of aggressive rehabilitation at the Transitional Learning Center round out the critical components of UTMB's efforts," Hulsebosch said.

James Tour, Ph.D., a chemist at Rice University's Smalley Institute for Nanoscale Science and Technology, said the grant will support his collaborative research of novel drug delivery systems to treat mild traumatic brain injury.

"Oxidative stress is a prominent feature of traumatic brain injury," Tour said. "We have developed a new antioxidant agent based on carbon nanotubes, and in collaboration with Dr. Thomas Kent of the Baylor College of Medicine we will examine the therapeutic potential of the agent to treat mild TBI."

J. Regino Perez-Polo, Ph.D., I. H. Kempner Professor and chair of Biochemistry and Molecular Biology at UTMB said that after 10 years of collaborative efforts among basic and clinical scientists who belong to the Mission Connect Consortium covering a broad spectrum of expertise, it is rewarding to have this opportunity to address a health issue of significance to our returning service men and women.

"Our ability to apply novel intervention strategies to nervous system trauma based on the cellular and molecular biology observations made over the years would suggest that we will be able to make an impact on the treatment modalities to be developed over the next five years," Perez-Polo said. "At UTMB, the neuroscience research community has a long tradition of excellence dedicated to the understanding of trauma to the nervous system. We are very happy to be able to make a contribution to this joint Texas effort in what is an exemplary example of translational efforts at UTMB."

Garland D. Anderson, M.D., UTMB provost and dean of the School of Medicine, said, "The institutions that make up Mission Connect have a long history of working together successfully. This significant grant is testament to the fact that our collaboration makes us more competitive for funding than any one of our schools would have been alone and, more importantly, it strengthens our ability to improve the lives of those affected by traumatic brain injury."

Matthew Rasband, Ph.D., associate professor of neuroscience at Baylor College of Medicine, said that the consortium is a remarkable mix of basic, translational, and clinical research. "The award is very forward-thinking since in addition to clinicians, it includes neuroscientists working to elucidate the very basic and fundamental causes of nervous system injury all the way down at the molecular and cellular level," Rasband said. "At present we know very little about how brain injury disrupts the connections and communication among neurons. The neuroscientists participating will fill this huge gap in our knowledge. Armed with this information and working together in a collaborative environment, clinicians and neuroscientists stand a much better chance of designing new and innovative treatments for traumatic brain injury."

In total, 25 researchers are part of the

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