Despite its importance in civilian and military health, there are no treatments to treat TBI. Recent research in my laboratory has focused on developing therapeutics to treat TBI. The pathophysiology of TBI is complex, we hypothesized that drug combinations may be more effective than monotherapy. We screened pairs Food and Drug Administration-approved drugs that had off-label efficacy against TBI. Drugs pairs were screened for synergistic improvement in a hierarchy of behavioral tasks (Abdel Baki, et al., 2009). The combination of minocycline and N-acetylcysteine synergistically improved both task acquisition and retention after TBI. (Abdel Baki, et al., 2010). Strikingly, neither minocycline nor N-acetylcysteine had any effect on task retention or memory. The drug combination, however, potently prevented memory deficits. One focus of the laboratory is to understand how these two drugs synergize to prevent memory deficits.
Both minocycline and N-acetylcysteine have been used clinically for decades suggesting that the combination can be safely dosed to TBI patients. Therefore, a second focus of the laboratory is to complete the necessary preclinical studies to bring minocycline and N-acetylcysteine to clinical trials.
Figure 1. Traumatic brain injury is prevented by minocycline (MINO) and N-acetylcysteine (NAC). A, Representative coronal brain sections. The impact site is indicated with an arrow. The scale bar corresponds to 100 μm. B, Representative images of corpus callosum stained with myelin-specific stain luxol fast blue. Myelin loss in TBI saline-treated brains was partially restored by treatment with MINO plus NAC.
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Samah Abdel Baki, M.D., Pdoctoral Fellow
Margalit Haber, B.S., Graduate Student
Stephen Thorpe, B.S., Medical Student
Chair, Congressional Directed Medical Research Program (CDMRP), Neuroprotection Study Section, Psychological Health/Traumatic Brain Injury investigator-initiated awards (2007)
Member, CNP/BLIRP-2 Study Section, Henry M. Jackson Foundation (2008)
Member, CDMRP Psychological Health/Traumatic Brain Injury #5 (2008)
Chair, CDMRP ATTDA-Psychological Health/Traumatic Brain Injury (2008)
Member, NINDS Workshop on Combination Therapies for Traumatic Brain Injury (2008)
Member, CDMRP Psychological Health/Traumatic Brain Injury Clinical Intervention Research #1 (2009)