Identifying Biomarkers of Brain Injury

“Our long-term goal is to make this test so simple it can be used as a biomarker by anyone, anywhere.” Daniel Lim, MD, PhD

Developing a diagnostic blood test for mild traumatic brain injury (mTBI) by detecting  long non-coding RNAs was the goal of this project. Since many of these molecules are expressed abundantly in the brain, they could serve as a biomarker of brain injury. Such diagnostic technology could improve the care of millions of patients with mTBI by providing a more accurate, less subjective test for brain injury.

Concussions are common: A child bangs her head playing soccer, a driver hits his head during a car accident. While most are mild, even a single concussion can cause long-term problems.  

The trouble is, diagnosing a concussion is challenging. In the ER, a doctor will ask:  What’s your name?  Where do you think you are? What’s today's date? Currently, the answers to those questions are our best test for concussion because a CT scan may not be sensitive enough. Even highly skilled doctors often do not know whether a concussed patient should stay in the hospital or can safely go home. 

Given the high incidence of concussions – nearly 5 million Americans suffer one every year – and lack of a definitive test, Dr. Dan Lim and Dr. Geoff Manley sought to find a biomarker that would reveal whether a patient requires intensive neurological treatment – or not. 

Working together, the two neurosurgeons approached the diagnosis process from a new direction by focusing on the meninges, the soft, wraparound brain covering that they had not closely examined before. They knew that when an organ is injured, certain molecules leak into the blood. If those molecules are detected in a blood test, they signal the occurrence of an injury. The brain is separated from the body by the blood-brain barrier, but outside this barrier is the meninges, which leaks molecules into the body’s circulation system when the brain is injured. 

The team analyzed the meninges of about 100 people who had recent concussions and people who didn’t to see whether newly discovered RNA molecules were present in the blood. They found exactly what they were looking for: Even though a CT scan did not detect a concussion, the blood test revealed RNA molecules had leaked from the meninges, indicating that an injury requiring hospitalization had occurred. 

“We still have some work to do – testing it on more patients, making the test faster and cheaper,” said Dr. Lim. “But we’re getting there. Our long-term goal is to make this test so simple that it can be used by anyone, anywhere.”  

He credited the Weill Innovation Award with helping unite his team with Dr. Manley’s to work toward developing an incredibly useful test that could ultimately prevent disabilities and save lives. 

UCSF Weill Awards

Joseph DeRisi, PhD; Sam Pleasure, MD, PhD; and Michael Wilson, MD