Grant: Project Grant

PTSD (post-traumatic stress disorder) occurs in some people after severe traumatic events such as sexual assault or military combat. Patients suffer nightmares, flashbacks, and can be very anxious, avoiding reminders of the traumatic event. In severe cases, PTSD can be completely disabling and current treatments are often ineffective. The main treatment for PTSD consists of repeatedly exposing the patient to cues related to the trauma with the hope that they will become less sensitive to these triggers. Some antidepressant medications can also be helpful, but better treatments based on the causes and disease mechanisms for PTSD are needed. We have recently discovered that two proteins involved in the stress response system can bind together and form a complex, and that this protein complex is elevated in patients with PTSD (but not in healthy controls or people exposed to trauma but who don't develop PTSD). We have also created a tiny protein molecule called a peptide that can block this interaction and separate the complex. We have used a mouse model of PTSD that involves exposing the animals to fearful stimuli, after which they develop anxious behaviours similar to human PTSD. Our peptide can block the emergence of PTSD-like behaviours in mice after exposure to fearful situations, suggesting that our peptide could actually prevent PTSD if given after a traumatic event. This grant application proposes a series of experiments to investigate the detailed mechanism underlying these preliminary results. We will investigate if other proteins are involved in this complex, how downstream signaling pathways are affected, and how stress hormones like cortisol affect the proteins in the complex. We will also take the first steps towards testing our peptide as a treatment for PTSD by determining the optimal timing and delivery of the peptide. If successful, our work may lead to the first preventative treatment for PTSD that is based on new knowledge of disease mechanisms