Traumatic brain injuries (TBI) can have devastating long-term effects, and research into effective treatments remains a critical area of study. In a significant step forward, Penn Medicine researchers have been awarded an $8 million grant from the Department of Defense to identify new biomarkers for TBI, paving the way for targeted treatments and improved patient outcomes.
A New Approach to TBI Treatment
Traditionally, TBI treatments have focused on symptom management rather than addressing the specific brain damage sustained by each individual. Douglas H. Smith, MD, professor of Neurosurgery, and Ramon Diaz-Arrastia, MD, PhD, professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania, are leading efforts to change that. They have launched the program to Characterize Evolving Endophenotypes of Degeneration after TBI (PROCEED TBI) to study the underlying mechanisms of brain injuries and develop personalized treatment approaches.
"Currently, we treat individuals based on the severity of their symptoms rather than the specific damage to their brain," said Dr. Smith. "By identifying distinct biomarkers for different forms of brain injury, we hope to enroll patients in clinical trials targeting their specific condition, ultimately leading to more effective treatments."
Understanding the Impact of TBI
A TBI can occur from a bump, blow, jolt to the head, or a penetrating injury, causing severe and often lasting damage. Some of the most common forms of brain injury include:
- Diffuse Axonal Injury (DAI): Damage to nerve fibers in the brain's white matter, often leading to loss of consciousness or coma.
- Hemorrhage: Bleeding caused by shearing or laceration of blood vessels.
According to the Centers for Disease Control (CDC):
- More than 214,000 TBI-related hospitalizations occurred in 2020.
- Over 69,000 Americans died from TBI-related injuries in 2021.
- Certain groups, including service members, veterans, racial and ethnic minorities, and lower-income individuals, are at a higher risk of experiencing severe long-term effects.
Many TBI survivors face ongoing health issues such as seizures, neurodegenerative diseases, dementia, depression, and bladder or bowel dysfunction. Identifying new biomarkers could help address these chronic complications more effectively.
The PROCEED TBI Study
The PROCEED TBI initiative is building on decades of research at Penn Medicine's Center for Brain Injury and Repair (CBIR), which has already uncovered critical mechanisms behind DAI and post-injury coma. The program will examine pathological changes in the brain over six months following TBI using a diverse dataset, including:
- Post-mortem human brain samples
- MRI scans of living patients
- Blood samples from TBI survivors
- Large animal models
The study has four key objectives:
- Identify the primary forms of brain damage post-TBI, including nerve tract degeneration and persistent blood vessel damage.
- Assess imaging techniques, such as MRI, for their ability to detect these injuries accurately.
- Determine blood biomarkers that indicate specific types of brain damage.
- Correlate imaging and blood biomarkers with injury severity and symptoms to pinpoint future treatment targets.
A Future of Personalized TBI Treatment
"With advanced brain imaging and biomarker tools, we aim to understand how TBI impacts each individual differently," said Dr. Diaz-Arrastia. "In an ideal scenario, these biomarkers would help us assess the extent of brain injury and predict long-term risks. This would allow clinicians to prescribe precise treatments immediately rather than waiting for symptoms to emerge."
By investing in biomarker-driven treatments, researchers hope to develop personalized medicine strategies that can prevent and mitigate long-term complications of TBI.
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