AFRL teams with Cincinnati Children's Hospital for kidney biomarker research

  • Published
  • By John Schutte
  • AFRL Human Effectiveness Directorate
In the realm of medical science, four years can be a lifetime--the difference between life and death for those whose health depends upon medical research results.

Biotechnology researchers at the Air Force Research Laboratory hope to save that much time in their quest for a hand-held biochemical monitor by joining forces with the Cincinnati Children's Hospital Medical Center to share data and research capabilities.

Under a Cooperative Research and Development Agreement (CRADA), Dr. Prasad Devarajan, director of nephrology and hypertension at the Cincinnati Children's Hospital, is providing four existing human kidney biomarkers to researchers at AFRL's Human Effectiveness Directorate, Biosciences and Protection Division.

Biomarkers are substances the body produces such as ribonucleic acid, proteins, organic compounds (such as glucose) found in blood, saliva and other bodily fluids or tissue. These substances are key to development of an accurate near real-time monitoring device.

"This saves us three or four years," said Dr. Camilla Mauzy a predictive biotechnologist with the Human Effectiveness Directorate, Applied Biotechnology branch. "Dr. Devarajan is doing human studies, so if we can get those biomarkers and test them in our system it will be a tremendous advantage."

Dr. Mauzy said scientists can spend two to three years identifying a biomarker and another 18 to 30 months developing an assay--an analytical methodology that scientists use to specifically and precisely measure the quantity of individual biomarkers in bodily fluids. Researchers use assays to prove that the quantity of a particular biomarker accurately reflects the disease/decrement state in human samples.

AFRL researchers envision a palm-sized detection device that will alert warfighters or civilians who are exposed to biological or chemical warfare agents. The device would measure biomarkers to determine a person's health condition or level of exposure to stress-causing agents such as heat, cold, fatigue and chemical or biological agents.
Dr. Devarajan's work is directed toward biomarker discovery for early detection of acute kidney failure, a common condition present in about five percent of all hospital
admissions and associated with mortality rates of up to 80 percent.

"Early identification of acute kidney failure is the key to instituting effective preventive and therapeutic measures in a timely manner," Dr. Devarajan said. "Developing early predictive biomarkers for this serious condition will significantly improve patient health and lower deaths."

"The work carried out by Dr. Devarajan represents a pioneering effort to move medicine into a more individualized and prospective mode," said Dr. Thomas Boat, chairman of pediatrics and director of the Cincinnati Children's Research Foundation. "Called 'personalized and predictive medicine,' this approach to care promises to improve health outcomes and reduce costs by providing critical information in a more timely fashion."

AFRL research is currently focused on biomarkers released in response to specific organ toxins in animal models such as lab rats. The opportunity to bring known human kidney biomarkers into the AFRL biomonitor program benefits both AFRL and Cincinnati Children's Hospital, according to Curt Grigsby, a research chemist with AFRL.

"Dr. Devarajan doesn't have the instrumentation that we do, so we may find things that he didn't that would enhance his research," Mr. Grigsby said, referring to his lab's state-of-the-art hybrid mass spectrometer, which gives Air Force scientists the ability to probe much deeper to resolve chemical entities at a molecular level.

AFRL researchers will use the human samples from Dr. Devarajan not only for their intrinsic value as biomarkers, but to develop a "pipeline" for incorporating future biomarkers, Mr. Grigsby said.

"Our whole project is not simply about solving a problem but setting up a process for migrating newly identified biomarkers as quickly as possible into the monitor device," Mr. Grigsby said. "So by putting these assays into our hand-held monitor we both create a new field-ready system capable of identifying kidney damage and we set up a pipeline for integrating into the platform the protein biomarkers that we identify in-house."

The time savings should also increase AFRL's research efficiency, Dr. Mauzy said.
"If we can get well characterized and well-defined assays into our device and move forward with its development, that gives us more time to work on our in-house assays and biomarker discovery," Dr. Mauzy said.

AFRL's partnership with Cincinnati Children's Hospital is conducted through a CRADA, which allows the two groups to share resources and data.