The UNC Institute for Trauma Recovery in the UNC Department of Psychiatry has been awarded a $3-million grant from the U.S. Department of Defense (DoD) to investigate the potential of a therapeutic agent to reduce the frequency and severity of acute stress disorder and post-traumatic stress disorder (PTSD). Acute stress disorder refers to the body's immediate response to trauma, whereas PTSD is the long-term effects of trauma.
"Historically, we have been able to provide emergency care to address immediate and long-term problems after visible wounds using tools such as sutures and antibiotics. However, we still have nothing to offer trauma survivors, whether in the emergency department or on the battlefield immediately after trauma, to prevent the development of 'invisible wounds'," said principal investigator Samuel McLean, MD, MPH, professor of psychiatry and emergency medicine and director of the Institute for Trauma Recovery at the UNC School of Medicine. "We need to investigate potential treatments like ACER-801 in an effort to better address these challenges."
The proposed OASIS trial will examine the safety and efficacy of ACER-801 (osanetant) to reduce acute stress response symptoms, posttraumatic stress disorder symptoms and behavioral changes among patients presenting to the emergency department after a motor vehicle collision.
Participating sites will include Washington University in St. Louis, University of Massachusetts Chan Medical School, Rhode Island Hospital, University of Florida College of Medicine - Jacksonville, and Indiana University School of Medicine. The study, proposed to begin in the first half of 2023, will evaluate the efficacy of ACER-801, which Acer Therapeutics licensed from Sanofi in 2019.
The OASIS trial builds upon a foundation of knowledge and infrastructure developed through the UNC-led, $40 million AURORA initiative. The AURORA study is a major national research initiative to improve the understanding, prevention, and recovery of individuals who have experienced a traumatic event. AURORA is supported by funding from NIH, One Mind, private foundations, and partnerships with leading tech companies such as Mindstrong Health and Verily Life Sciences, the healthcare arm of Google's parent company Alphabet.
"We are proud to be partnering with a leading academic institution in the field of trauma recovery as we begin exploring ACER-801 as a treatment option to reduce the frequency and severity of acute PTSD," said Adrian Quartel, MD, FFPM, Chief Medical Officer of Acer. "The data from thousands of motor vehicle collisions collected through the AURORA initiative should allow us to better predict the correlation of the emergence of acute stress disorder or PTSD symptoms following a motor vehicle collision."
Added Brandon Staglin, President of One Mind "We are thrilled to see how our funding to the AURORA initiative over the last five years is accelerating further advancements such as the OASIS Trial. The targeted outcomes of the OASIS Trial are the types of results that One Mind supports and of incredible value to anyone who experiences trauma and traumatic stress."
Acute and chronic stress disorders can affect both civilian and military populations. According to the National Center for PTSD, in the US about 60% of men and 50% of women experience at least one trauma in their lives. In the United States alone, one-third of emergency department visits (40-50 million patients per year) are for evaluation after trauma exposures, and in a 2014 study involving 3,157 US veterans, 87% reported exposure to at least one potentially traumatic event during their service.3 Moreover, as many as 500,000 US troops who served in wars between 2001 and 2015 were diagnosed with PTSD.
Scientific rationale for OASIS:
The Tacr3 gene encodes tachykinin receptor 3 (NK3R), which belongs to the tachykinin receptor family. This family of proteins includes typical G protein-coupled receptors and belongs to the rhodopsin subfamily. NK3R functions by binding to its high-affinity ligand, Neurokinin B (NKB), which is encoded by the Tac3 (human) gene.
The role of NKB-NK3R in growth and reproduction has been extensively studied, but NKB-NK3R is also widely expressed in the nervous system from the spinal cord to the brain and is involved in both physiological and pathological processes in the nervous system. In animal models, Tac2 mRNA levels are rapidly up-regulated during fear consolidation 30 minutes after fear conditioning, and subsequent NKB-NK3R activation can lead to over stress sensitization and the consolidation of fear, and treatment with osanetant has been shown to block a critical fear/stress sensitization step in the brain. An effective therapeutic to reduce acute and persistent/long-term psychological and somatic symptoms would fulfill a large unmet need.
