Temple Scientist Awarded Grants for Lung, Brain Injury Studies
A researcher at Temple University School of Medicine has been awarded a pair of grants totaling nearly $4.5 million from the Office of Naval Research (ONR) to study the use and effectiveness of a type of chemical in helping protect the lungs of soldiers and other military personnel from the effects of high altitude. In a separate project, she plans to examine the chemical’s usefulness in lessening the impact of traumatic brain injuries.
Marla R. Wolfson, PhD, Professor of Physiology, Pediatrics and Medicine at Temple University School of Medicine, has received grants for approximately $2.5 million and $1.9 million, respectively, over three years. The larger of the two grants will support research to examine the use of chemicals called perfluorochemicals (PFC) to deliver certain types of drugs that can be inhaled and distributed throughout the lungs to both protect and treat altitude-related health problems. PFCs are liquids that can inflate the lung at low pressure, carry large amounts of oxygen and carbon dioxide, help deliver drugs in the lung, and have unique thermal properties.
“There’s a great need for a common technology to address injuries suffered by military personnel in environmentally stressful locations, such as high altitude, where there can be a lack of oxygen,” said Wolfson. “Many injuries away from the field can be readily treated, but the need to treat at the site where the injury occurs sometimes can make all the difference to a patient’s recovery.”
At high altitude, air pressure and oxygen content are less than normal, and the pulmonary system redirects blood flow to help breathing. In the military, soldiers might be asked to deploy to high altitudes without time to acclimate their bodies to these changes in conditions. Investigators will use various research models to test the use of PFCs in treating soldiers’ acute lung problems and in reducing their vulnerability to conditions that might require immediate attention.
The researchers will also examine three approaches using PFCs to attempt to lessen complications in the lungs from high altitude/low oxygen situations, including the use of three biologics approved by the FDA. In one study, they will test if PFCs delivered alone by aerosol spray improve the “ventilation-perfusion relationship,” which is important to maintaining the appropriate flow of oxygen into the lungs’ blood vessels and the simultaneous removal of carbon dioxide.
In a second study, Wolfson’s team plans to test whether sprayed/inhaled PFCs can effectively deliver drugs to offset the effects of blood vessel narrowing. Lastly, they hope to show that PFCs sent by aerosol spray can effectively deliver a drug to reduce fluid buildup.
“The military needs a rapidly usable, practical technology available in the field that can treat some of these symptoms associated with difficult environmental conditions,” she said. “We think our concept of inhalable drugs distributed by PFCs will provide a solution.”
In a second ONR grant-supported project, Wolfson and her colleagues will study novel ways to protect military personnel from traumatic brain injuries and lung damage resulting from explosive devices. The investigators will use research models to examine the effectiveness of PFCs in helping protect the brain and lung from the secondary effects of “blast injuries,” hoping to both reduce the effects of injuries and prevent subsequent damage from inflammation. One of the techniques they will test involves rapidly and non-invasively cooling the brain, which has been shown in research studies to offer some protection from further damage after injury.
“We need to develop better approaches to protecting the brain and lungs from blast injuries, which is an ongoing problem for military deployed in combat areas,” Wolfson explained. “There’s a great need for having effective treatments available at the injury site in the field. Our results can have an impact in prevention and treatment of a wide range of such injuries in many different settings.”
Traumatic brain injury is a leading cause of death and disability in military personnel, and lung injuries are the leading cause of death secondary to explosions. Approximately 1.4 million people in this country are affected by traumatic brain injury every year.
Complications involving blast injuries can be wide-ranging in nature, Wolfson explained. While traumatic brain injury can be the result of a blunt force on the brain or chest, other more indirect injuries can occur from “pressure waves” to the head or body.
Investigators will ask whether delivering PFC liquids directly into the lungs can halt or reduce tissue damage and inflammatory processes after blast injuries. They will also test the ability of PFC liquids given in aerosol form to help rapidly cool the brain, again, to lessen complications from injuries by reducing swelling and inflammation.
“Traumatic brain injuries are a particularly serious problem, with far-reaching consequences,” Wolfson said. “Our projects are broad in scope, and will have widespread applications beyond just the military, including, for example, head injuries associated with stroke, sports or other trauma. Our goal is to translate our findings into clinical trials of new therapies in people.”