Posttraumatic Stress Disorder (PTSD) is an anxiety disorder that can develop after exposure to a traumatic event such as , natural disaster, physical or sexual assault, motor vehicle accidents, or military combat. Hallmark PTSD symptoms include nightmares or repetitive thoughts of the event, avoiding reminders of the event, and being anxious or easily startled. The lifetime prevalence of PTSD is estimated at 6.8% of the US population and as high as 30% in military veterans. PTSD affects not only the trauma survivor, but their family and their interpersonal relationships. The available treatments for PTSD include pharmacotherapy and psychotherapy, used alone or in combination. It is difficult for PTSD patients to achieve complete remission, so new treatment options are still needed.

Marinus has entered into a public-private relationship with the INTRuST consortium, a group of PTSD treatment centers in the U.S. that has received government funding to evaluate promising new treatments for PTSD (http://intrust.sdsc.edu). Ganaxolone is currently being tested by the INTRuST consortium in PTSD patients. The trial is currently enrolling.

PTSD Pharmacology

Ganaxolone is a powerful positive allosteric modulator of GABA-A receptors with potency and efficacy comparable to the endogenous GABA-A receptor neuromodulator allopregnanolone. As with allopregnanolone, ganaxolone potentiation of the GABA-A receptor occurs at a site distinct from the benzodiazepine binding site.

Decreased levels of allopregnanolone increases anxiety-like behaviors and aggression, as well as, contextual fear conditioning in rodent models; administration of selective serotonin reuptake inhibitors in turn, markedly enhances neurosteroidogenesis and normalizes both allopregnanolone levels and these aberrant behaviors . Allopregnanolone levels correlate inversely with PTSD re-experiencing symptoms and negative. Treatment with ganaxolone should normalize neurosteroid levels and alleviate PTSD symptoms.

To learn about our clinical trials, please click here.