Scientific Rationale

An overactive amygdala, the brain’s fear center, is one of the hallmarks of PTSD and is responsible for disease pathology. Human and preclinical studies have long shown that trauma causes high activity in the amygdala. While surgical intervention to balance amygdalar activity have proven successful for the most severe cases, no approved or experimental PTSD medications directly target amygdala hyperactivity.

The research underlying the current PTSD investigations at Neurovation Labs utilized a robust model of PTSD in rodents called stress-enhanced fear learning (SEFL). In the SEFL model, an acute, severe, and unpredictable stressor permanently sensitizes subsequent conditional fear learning. The procedure is likened to a PTSD trigger, like a car backfiring, setting off a disproportionate fear reaction in a patient suffering from PTSD. Such a reaction is the crux of PTSD symptomatology and is captured in the SEFL rodent model along with the other PTSD symptoms identified in the DSM-V checklist.

SEFL is a unique PTSD model in that it combines multiple behavioral techniques. Because of this, we can truly capture all aspects of the disorder, including exaggerated or sensitized fear, blunted emotional reactivity, dysregulated HPA axis activation, anxiety and depressive behaviors, as well as increased consumption of alcohol.

Dr. Perusini together with Dr. Fanselow found that after a traumatic experience, there are long-term increases in calcium-permeable, ionotropic glutamate receptors in the amygdala. These receptors are the neurophysiological correlate of activity after a learning event. The result of the persistent increase is the observation that we always see in those suffering from PTSD: an overactive amygdala. This regional receptor increase provides an exceptional target for therapeutic intervention. Neurovation Labs is building on these discoveries to develop a treatment that focuses on the physiological cause of PTSD, as well as a companion diagnostic to determine those who would benefit from the treatment. The company also aims to tackle other CNS disorders that implicate the glutamate system.

Perusini et al., 2015