Novel pharmacological treatments for TBI
Aim: To build a data set from in vitro studies with human cells and tissues to demonstrate that neuroinflammatory cells primed by TBI may be inhibited by antagonising the P2X7 receptor. This data set will then be used to support performance of a clinical trial in patients with TBI.
Background: Despite obvious need there are no approved pharmacological treatments for TBI. The primary insult in TBI is difficult to treat, but a reduction in secondary non-mechanical damage of surrounding brain tissue offers greater potential therapeutic opportunities.
The neuroinflammatory response associated with TBI is activated immediately after injury with potential neuroprotective but also damaging effects and persists up to years. An imbalance of neuroinflammatory processes further stresses surviving cells amplifying brain damage. These delayed secondary inflammatory processes, which develop over hours to days, are potentially amenable to drug treatment.
Method: The team will execute in vitro studies with human cells and tissues, including primary cells harvested during neurosurgical procedures, to challenge the hypothesis that patients with TBI display activated microglia that are more sensitive to modulation via the P2X7 receptor to promote neuroinflammation, contributing to neuronal damage and loss in the penumbra.
The team will also formulate a case to evaluate the efficacy of a P2X7 receptor antagonist to limit the neuroinflammatory response to TBI with a corresponding reduction in brain damage and work with Pfizer to evaluate the utility of a clinical stage drug to treat TBI.