TGen, Barrow Neurological Institute and Phoenix Children’s Hospital receive $4 million grant to study genetic basis of brain injuries
NIH grant to identify biomarker for secondary injuries associated withruptured brain aneurysms and subarachnoid hemorrhage
Phoenix, Arizona – 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.
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About Phoenix Children's Hospital
Phoenix Children's Hospital is Arizona's only children's hospital that is ranked in U.S. News & World Report's Best Children's Hospitals. Phoenix Children's provides world-class inpatient, outpatient, trauma, emergency and urgent care to children and families in Arizona and throughout the Southwest. As one of the largest children's hospitals in the country, Phoenix Children's provides care across more than 75 pediatric specialties. The Hospital is poised for continued growth in quality patient care, research and medical education. For more information about the hospital, visit www.phoenixchildrens.org.
About Barrow Neurological Institute
Barrow Neurological Institute at St. Joseph's Hospital and Medical Center is internationally recognized as a leader in neurological research, diagnosis and patient care. Its world-renowned physicians treat patients with a wide range of neurological conditions, including brain and spinal disorders and injuries. More brain surgeries are performed at Barrow than any hospital in the United States and the Institute trains more neurosurgeons than anywhere in the world. St. Joseph's is consistently voted among the top hospitals in the United States for neurology and neurosurgery.
Carmelle Malkovich, Senior Public Relations Specialist
St. Joseph's Hospital and Medical Center
Barrow Neurological Institute
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with cancer, neurological disorders and diabetes, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.
Steve Yozwiak, TGen Senior Science Writer
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. Research reported in this publication was supported by the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UH2TR000891. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.