OCT 04, 2016

Using PET Technology and Protein Tracers to See CTE

WRITTEN BY: Brenda Kelley Kim
Chronic traumatic encephalopathy (CTE) is a neurodegenerative brain disease that has gotten a lot of attention in the press and in the medical community in the last few years. Multiple studies connect the disorder to repeated traumatic blows to the head that result in concussion. A post-mortem study of the brains of NFL players  who donated their bodies to medical research showed that 96% of them had the disease. CTE can cause memory loss, depression, anxiety and eventually death. At this time it can only be definitively diagnosed by examination of brain tissue after death.
 
New information from a team of researchers at Mount Sinai however, could allow doctors to diagnose it while a patient is still alive.  Using positron emission tomography (PET) scans with an experimental imaging agent called [18 F]-T807 (or Avid 1451), CTE can be effectively diagnosed in a living patient. This according to a proof-of-concept study conducted at the Icahn School of Medicine at Mount Sinai. The research was published on September 27, 2016 in the journal Translational Psychiatry and the authors hope it can lead to treatments for the devastating disease
 
A living, 39-year-old retired National Football League (NFL) player who had experienced 22 concussions and exhibited clinical symptoms consistent with chronic traumatic encephalopathy (CTE) agreed to undergo PET scans with the imaging agent to see if any brain changes could be seen definitively. The imaging agent T807 is a ligand, which means it’s designed to latch onto a protein called tau that accumulates in the brain of a person with CTE.  While build-up of the protein tau is associated with many neurological impairments, patients who have CTE show a distinctive pattern of tau build-up.

These patterns were detailed a panel of top notch neurologists and researchers commissioned by the National Institute of Neurological Disorders and Stroke (NINDS). They were brought together to develop the diagnostic criteria for CTE based on samples of postmortem brain tissue. The tau deposits in the wrinkled surface of the brain have a specific pattern and while this can be seen in a post-mortem exam, the Mount Sinai work with ligands and PET scans to reveal a pattern that matches the NINDS criteria is a first.
 
In a press release about the study, last author Sam Gandy, MD, Director of the Center for Cognitive Health and NFL Neurological Care Program at the Icahn School of Medicine at Mount Sinai said, "Our study participant's scan is the first to reveal during life a pattern of tau imaging that outlines the wrinkles and folds of the living brain, just like the 'pathognomonic pattern' described by the NINDS panel as diagnostic of a brain with CTE. When fully validated, this new ligand has the potential to be used as a diagnostic biomarker and represents an exciting development in the detection and tracking of CTE."
 
Colleague and first author of the study Dara L. Dickstein, PhD, Assistant Professor of Neuroscience, and Geriatrics and Palliative Medicine at Mount Sinai added,  “This research is in its infancy. Whether or not the pathology can be reversed or halted is something we have yet to determine and these new tauopathy PET scans may be able to help in this endeavor.”
 
Mount Sinai is currently working with 24 patients and hope to begin clinical trials to identify CTE via PET scans with the ligand agent and possibly test medications that are being developed to break up tau deposits. CTE exacts a huge price on those who suffer from it as well as their families and caregivers. Check out this video to see the biology and history of what we know about this terrible disease
https://youtu.be/AaHObVz9U44
 
Sources: Mount Sinai Hospital, Translational Psychiatry, NY Daily News, Healthline