In an effort to lower medical costs, identify patients at risk for injury, and speed patient recovery, scientists will attempt to identify a molecular signal that indicates severity of brain-injury during a $4 million, five-year federal grant to Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center, Phoenix Children’s Hospital and the Translational Genomics Research Institute (TGen).

The molecular profile — comprised of RNA, the body’s relay messenger between DNA and protein — could help identify which patients are most at risk for vasospasm after hemorrhagic stroke.  Hemorrhagic stroke can occur as:

•    Subarachnoid hemorrhage, or the bleeding into the area between the brain and a thin membrane that covers it.
•    Ruptured brain aneurysm, which is an abnormal bulge or ballooning in the wall of an artery within the brain.

By identifying this RNA molecular marker, a new standard of individualized care could be established, enabling medical teams to respond more rapidly to quickly changing health conditions, and allowing earlier intervention to prevent a secondary injury from occurring.

“We hope this study will lead to less injury, less testing and cost, and shorter stays in the hospital,” said Dr. Yashar Kalani, M.D. and Ph.D., a resident physician in Neurological Surgery and assistant professor at the Barrow Neurological Institute and one of the study’s principal investigators. Additional investigators at Barrow include Drs. Robert Spetzler, Peter Nakaji, Felipe Albuquerque and Cameron McDougall.

Vasospasms are characterized by bleeding in the brain that causes irritation and nearby blood vessels to spasm and narrow. This decreases blood flow to the brain, which can result in damage or even death to parts of the brain.

Only about half of patients with brain-aneurysm ruptures survive, and those who do survive often are severely disabled for life. In the 10 days following such ruptures, blood vessels can narrow, leading to loss of oxygen, strokes and brain damage.

“If we knew what is happening during this period, we might be able to intervene and prevent the secondary injury,” Dr. Kalani said.

Barrow will provide patient care and collect blood and spinal fluid samples that will be analyzed by TGen. A recent TGen study showed spinal fluid could be sequenced for RNA biomarkers. Samples will be checked daily to compare and identify changes.

Another part of the study will be conducted at Barrow’s partnership with Phoenix Children’s Hospital, where researchers will investigate the effects of intraventricular hemorrhage — another form of bleeding in the brain — in newborn babies. Intraventricular hemorrhage in newborns occurs secondary to diminished blood flow and oxygen delivery to the brain. Intraventricular hemorrhage is associated with the development of hydrocephalus and damage to the brain that can result in cerebral palsy or other types of motor and cognitive delays.

“This study will get us one step closer to learning what is unique in pediatric stroke so we can provide the best quality care and improve the long term outcomes for these children,” said Dr. P. David Adelson, one of the principal investigators of the study at Barrow Neurological Institute at Phoenix Children’s Hospital.

“In addition, as this study progresses, we want to know how to identify children at risk, and how they differ from adults with similar conditions, this will not only help us to be more accurate at providing current treatments but to develop new ones.” said Dr. Jorge Arango, an investigator affiliated with Barrow Neurological Institute at Phoenix Children’s Hospital and with the University of Arizona College of Medicine-Phoenix.

In the study of both adults and children, TGen researchers will use state-of-the-art sequencing — to analyze RNA transcripts, searching for biomarkers that could identify at-risk patients.

RNAs are cell molecules made from DNA that help create proteins.

“There has been an explosion over the last several years in our understanding of the functional and regulatory mechanisms modulated by RNA” said Dr. Kendall Van Keuren-Jensen, Ph.D., an Assistant Professor in TGen’s Neurogenomics Division and also a principal investigator in the study funded by the National Institutes of Health (NIH).

“We are very excited about the potential for extracellular RNAs to provide us with accessible information about the mechanism of disease, and in doing so, provide us with pre-symptomatic markers of disease,” said Dr. Matt Huentelman, Ph.D., an Associate Professor in TGen’s Neurogenomics Division and also a principal investigator on the project. “In the best-case scenario, these markers can be coupled with an improved clinical management of the disease, too. In a nutshell, that is what we are exploring under this new grant award.”

This type of study is now possible because of continuing improvements in optics and computer speed that enables TGen’s cutting-edge technology to sequence at ever-faster rates and at ever-lower costs. While it took 13 years and $2.7 billion to spell out the first human genome, such sequencing can now be done in a matter of days and for less than $5,000.

Additional partners in the study include: University of California, San Francisco; and Stanford University.