Combination Therapies for Traumatic Brain Injury Workshop
Sponsored by the National Institute of Neurological Disorders and Stroke, the National Institute of Child Health and Development, National Institute of Heart, Lung, and Blood, and the Veteran’s Administration
February 27 – 28, 2008
Traumatic brain injury (TBI) is a major medical problem for which there are no proven interventions. Neuroprotection remains a high priority for TBI, but all Phase III clinical trials to date have failed. A major reason cited for the failures is that the evolving, constellation of pathophysiological mechanisms associated with TBI cannot be addressed with a single “magic bullet”. Despite this realization, and the dramatic gains that have resulted from the use of combination therapies for other medical disorders, almost all preclinical and clinical studies for TBI continue to evaluate single interventions. In order to facilitate research on combination therapies for TBI, the NIH convened a workshop in February, 2008. The goal was to develop a rational strategy for selecting and testing combination therapies for TBI. Specifically, workshop participants were asked to: 1) identify the issues and challenges of testing combination therapies in clinical and pre-clinical studies; and 2) propose research methodologies and study designs to overcome these issues; and 3) describe potential synergistic and antagonistic effects of combining some of the currently most promising mono-therapies. Break out groups discussed and recommended strategies for testing combination therapies using in vitro and in vivo models as well as clinical trials. Major recommendations included 1) developing an in vitro high throughput screening platform for the evaluation of mono- and multi-drug therapies; 2) developing guidelines for pre-clinical studies; 3) selecting combination therapies based on their potential for additive effects when administered either at the same time or at different times; and 4) using therapies that target multiple mechanisms until it is possible to more finely discriminate between the multiple, evolving pathophysiological processes that occur following TBI. The next steps are to publish the workshop proceedings in the Journal of Neurotrauma and to present them at the National Neurotrauma Society meeting in 2008. Those attending considered this an important first step toward testing combination therapies for TBI.
Last Modified April 30, 2008