Tim Mhyre: Pioneering Blood Tests to Detect and Treat Brain Diseases
Brains are mysterious things. Hidden behind the protective skull and blood-brain barrier, there is no way to effectively diagnose many of the disorders that cripple it – much less predict their development.
But Tim Mhyre, PhD, thinks there is a natural portal into the brain that can act like a crystal ball of sorts. And that is the blood. Examining this most essential fluid already tells physicians about heart attack risks, as well as infections and other maladies.
So he asks – why can’t it tell us about Alzheimer’s and Parkinson’s disease, diagnosed in about six million Americans, as well as traumatic brain injury (TBI), a growing public health concern that affects another 1.4 million a year? Damage seen in TBI comes from car crashes, falls, sports injuries, as well as increasingly from military assaults, such as roadside bombings.
What is common to these disorders is that they all involve inflammation in the brain, and, furthermore, these diseases promote a breakdown in the blood-brain barrier that normally restricts passage of biological materials in to and out of the brain. So these substances leak into the blood, Mhyre says, and can be collected through a simple blood draw in the arm. Examining activated immune system cells shuttling to and from the brain in blood may also offer information to predict development or severity of disease, which can then guide treatment.
“This won’t be a Star Trek tricoder solution to diagnosis, but it could offer an invaluable insight into what is going on in the brain,” says Mhyre.
Howard J. Federoff, MD, PhD, executive vice president for health sciences, agrees. He is Mhyre’s colleague and former mentor who recruited him to Georgetown from the University of Rochester shortly after Federoff did the same in 2007. Mhyre received his PhD in neurobiology and anatomy in 2000 from the University of Rochester, and he credits Federoff with setting his career path.
In 2008, Federoff received a $3.1 million grant from the NIH to lead a collaboration of researchers – including Mhyre – to develop early detection methods for Alzheimer’s disease, which includes examining blood samples from patients. And earlier this year, under Federoff’s leadership, Mhyre and other neuroscientists were awarded a five-year, $15.2 million grant by the Department of Defense (DOD) to help understand and improve treatment of TBI. This grant includes other scientists from the University of Rochester and from a new collaborator, the Institute for Systems Biology in Seattle, which has pioneered a systems approach to understanding disease.
In these grants, among other things, Mhyre and colleagues will be looking for blood biomarkers that will help predict if a person is developing Alzheimer's or Parkinson's disease at a stage where it could be effectively treated and whether someone with TBI will have a good or bad outcome, Mhyre says. “The mode of TBI injury is different for different people; one person may have fallen and hit his head in one place whereas a roadside blast can injure a brain in multiple ways,” he says. “So a variety of biomarkers may be needed to predict outcome.”
The TBI grant will be conducted in phases, starting out with collecting histories, brain scans, and blood samples from individuals coming into an emergency department in the District of Columbia with brain injuries. These patients will be followed to see how their brains heal – and how biomarkers change based on the course of the injury and treatment. The second phase will be conducted in soldiers with blast injuries. “We want to develop a toolkit that tells us how well a person is going to survive such an injury and how they progress,” Mhyre says.
“Using these new ideas to diagnose brain disorders in time to treat or possibly prevent damage is really exciting,” he says. “In the future, everyone may get a brain ‘blood test’ along with their cholesterol test.”
By Renee Twombly, GUMC Communications