Posted March 20, 2014
Thomas Kent, M.D., Baylor College of Medicine
James Tour, Ph.D., Rice University
Of the more than 1.5 million people who experience a traumatic brain injury (TBI) each year in the United States, as many as 75 percent sustain a mild TBI (mTBI). Mild TBI may cause long-term or permanent impairments and disabilities in a significant proportion of patients and is frequently seen in OEF/OIF Veterans. Oxidative stress is a prominent feature of mTBI, especially when complicated by hemorrhagic hypotension (combat mTBI), and a secondary factor that worsens outcomes after mild TBI. The excessive production of oxidative species is due to cellular toxicity and exhaustion of the brain’s built-in antioxidant system. There are currently no antioxidant therapies that have improved patient outcome following traumatic brain injury.
Dr. Kent and Dr. Tour are two investigators supported by the FY07 Psychological Health and Traumatic Brain Injury Mission Connect Multidisciplinary Research Consortium Award (Mission Connect). The two researchers are developing a novel antioxidant therapy for mTBI that uses modified carbon nanoparticles called PEG-HCCs (polyethylene glycol-conjugated hydrophilic carbon clusters) to reduce the oxidative stress following mTBI. PEG-HCCs are nontoxic to cells in culture and elicit a protective effect when those cells are exposed to lethal oxidative stress. PEG-HCCs can also be functionalized with targeting molecules, which could allow, for the first time, targeting of an antioxidant to damaged components of the “neurovascular unit.”
Drs. Kent and Tour, with Dr. Claudia Robertson (Baylor College of Medicine), utilized an animal model of combat mTBI developed within Mission Connect to conduct experiments with the goal of establishing PEG-HCC’s efficacy in vivo. Results to date have demonstrated that PEG-HCC treatment following mTBI rapidly restores cerebral blood flow and oxidative balance. Recent data also indicates that PEG-HCC treatment reduces the number of degenerating neurons in the brain following mTBI.
The PIs intend to move forward with development by performing the range of preclinical studies necessary to translate these results into an Investigational New Drug (IND) application and eventual confirmation in humans.