Choi awarded $1.6 million NIH grant to develop protein biomarkers for delayed cerebral ischemia

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A three-year, $1.6 million grant to identify patients at risk for a serious secondary neurological complication that can arise after subarachnoid hemorrhage (SAH) has been awarded to UTHealth Houston researcher H. Alex Choi, MD, by the National Institutes of Health (NIH).

Choi, associate professor and vice chair for neurocritical care with McGovern Medical School at UTHealth Houston, plans to discover, develop, and validate protein biomarkers for a complication after SAH called delayed cerebral ischemia (DCI).

“The goal is not only to develop biologic signatures to predict which patients will get worse, but also to identify which biological processes are causing these patients to worsen,” said Choi, a neurologist at UTHealth Houston Neurosciences. “The proteomic-based technology coupled with genetic techniques we’re using is novel and will help identify the low-abundance proteins missed by more traditional methods.”

SAH is a life-threatening, debilitating type of hemorrhagic stroke that affects approximately 50,000 Americans annually. It occurs when a cerebral aneurysm ruptures, bleeding into the brain’s subarachnoid space, which consists of cerebrospinal fluid, major blood vessels, and cisterns.

About 30% of patients who survive the initial bleed develop DCI – characterized by focal neurological deficits like loss of strength to move one side of the body, loss of ability to understand or express speech, difficulty with skilled movements, or blindness over half the field of vision. DCI typically occurs four to 21 days after stroke.

Though DCI is potentially avoidable, past studies targeting the condition have failed, largely because of the inability to predict which patients will develop DCI. Consequently, all SAH patients are observed for prolonged periods in the intensive care unit, leading to higher rates of in-hospital complications, potential delays in treatment, and misappropriated resources.

In previous studies, Choi’s research team has found a link between early elevated pathophysiological response, quantified by measuring plasma protein biomarkers, and the development of DCI. The researchers have also identified six plasma proteins that can predict DCI within 48 hours of SAH, and they have identified a combination of proteins that improved DCI prognostication.

With the NIH funding (Grant No. 1R61NS119640-01A1), Choi aims to identify and develop additional protein biomarkers for DCI. By the end of the study, he hopes to develop a blood test that accurately predicts DCI within 48 hours of SAH for clinical use.

“This will allow us to develop new therapeutics for that specific vulnerable population of patients,” Choi said. “If the patient isn’t at risk for these complications, they won’t have to stay in the ICU for two weeks, and they can avoid unnecessary procedures and medications, getting on the road to recovery much quicker.”

After the three-year grant period ends, Choi will receive an additional two years’ worth of funding to continue his research.

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