Repositioning Drug Therapies for Traumatic Brain Injury

Traumatic brain injury (TBI) is occurring more commonly and, according to the World Health Organization, with an estimated 10 million people affected annually worldwide, it will soon outstrip many common diseases as the major cause of death and disability. With a high morbidity and mortality, and no specific therapeutic treatment, TBI has become a pressing public health and medical problem. The pathology underpinning head injury is becoming increasingly better understood. As a consequence of mechanical forces inducing shearing and compression of neuronal and vascular tissue at the time of impact, a cascade of pathological events may then follow leading to further brain injury. This ensuing secondary injury may be amenable to intervention and is worsened by secondary physiological insults. Specific risk factors for poor outcome after TBI have been recognized. Some of these are established at the time of injury, such as age, gender, mechanism of injury, and presenting signs, whereas others, such as hypoxia, hypotension and hyperglycemia, are potential areas for medical intervention. Although prompt and specialist neurocritical care is associated with improved outcome, to date, no drug treatments have proved to be successful in improving outcome . Since it takes years, or even decades, to develop and receive approval for new compounds, the aim of this proposal will be to develop the critical preclinical data to support repositioning of two classes of drugs (I) gliptins and incretins, used to treat type 2 diabetes mellitus (T2DM) and (II) n-acetylcysteine (NAC) used to treat pulmonary inflammation.