Valproic Acid for Prolonged Field Care
In June, three MCIRCC multidisciplinary research teams received Prolonged Field Care Research Awards from the Department of Defense’s Combat Casualty Care Research Program (CCCRP). These awards call for the development of next-generation diagnostics, monitoring, resuscitation and stabilization methods for prolonged field care (PFC) and prolonged damage control resuscitation (pDCR). In June, we profiled research from Hakam Tiba, MD, who is using the eye as a window to the brain. We now turn our attention to Hasan Alam, MD, and his use of valproic acid (VPA) to minimize organ injury and prolong survival.
Most Americans are privileged in that if we suffer a serious injury, we’re able to call an ambulance and be rushed to the necessary level of care. Unfortunately, our troops abroad do not have that luxury. As wars become more dangerous, battlefields become more isolated.
In future war zone scenarios, the Department of Defense (DoD) anticipates it could take up to 72 hours to evacuate a soldier after they’ve suffered a severe injury. Because of this, it is critical to develop technologies and treatments capable of sustaining the injured long enough so they may be transferred to higher echelons of care.
Dr. Alam believes that VPA is a promising treatment option in this scenario. His lab specializes in using this FDA-approved, anti-seizure medicine to treat critical injuries including traumatic brain injury (TBI) and hemorrhagic shock.
As the leading cause of death for young people in the United States, researchers have been interested in the survival rate from accidental injuries for years. In particular, Dr. Alam was curious as to why some patients survive their injuries while others perish even after they’ve been treated. It is now believed that the activation of gene pathways and proteins in the body are essential in prolonging survival after an injury.
“When the body is injured, it disrupts the equilibrium. To try and maintain balance, a number of pro-survival pathways or genes are activated—but some patients do this more effectively than others. This pharmacological approach activates a number of these protective pathways within minutes, making survivors out of non-survivors,” explained Alam.
If administered in high doses, VPA first activates the pro-survival pathways almost immediately. Later, the patient’s protective genes are activated offering a delayed benefit to the patient. For TBI, this has been demonstrated to improve long-term neurological recovery and healing in large animal models. It is also beneficial for hemorrhage patients in sustaining their condition until they’re transferred to a field hospital.
Not only is VPA effective, it’s an ideal solution for the battlefield. The drug is easy to administer and requires no special storage. Because it has been in clinical use for more than forty years, it is widely available and inexpensive. In other words, it would be extremely feasible to see this treatment included in the packs of medics.
Alam is working with MCIRCC to expand the utility of VPA treatment. Among other ideas, he wants to develop a point-of-care device to test patients’ blood to determine their level of pro-survival genes and pathways.
“MCIRCC serves as a platform to connect you with people you would never otherwise reach. For many of my projects, MCIRCC has been very helpful in taking it to the level where we can start translating ideas to practical applications with tools and devices. MCIRCC opens up doors that wouldn’t have existed otherwise,” said Alam.
Alam and his team received $3 million in funding from the DoD for this study. First, they’re identifying the optimal dosage for treatment including the timing and amount needed to activate the pro-survival pathways. Secondly, they’ll test how long the treatment will sustain a critically injured patient. It is their hope that VPA will be able to meet the unique challenges of the battlefield, especially in that crucial 72-hour window.