Name:
Molecular imaging of tau pathology after traumatic brain injury with Nikos Gorgoraptis
Description:
Molecular imaging of tau pathology after traumatic brain injury with Nikos Gorgoraptis
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Duration:
T00H07M31S
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Upload Date:
2020-01-15T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[MUSIC PLAYING]
NIKOS GORGORAPTIS: So my name is Nikos Gorgoraptis. I'm a Clinical Lecturer in Neurology at Imperial College London (UK). So I do both clinical work with patients and research, trying to better understand cognitive impairment following traumatic brain injury (TBI), with a view to developing new treatments for it.
Segment:1 Why is this area of research an unmet need? .
NIKOS GORGORAPTIS: Although we are aware of the effects brain injury has on the brain, the brain injury itself has on the brain, we're increasingly realizing through post-mortem studies that brain injury can trigger new pathological changes that are progressive, causing cell loss and eventually dementia.
NIKOS GORGORAPTIS: The key pathological molecule in this process is the protein, tau, which has been seen in the brains of people after a single, severe, traumatic brain injury or multiple, milder brain injuries over a span of many years. But at post-mortem, it's way too late for our patients. So we need something that can detect tau protein during their lifetime, when it really matters-- as early as possible during their lifetime.
NIKOS GORGORAPTIS: And it's a really exciting time. Because now, we have techniques available that can detect tau in the brain during a person's lifetime. That's called tau positron emission tomography. And in the study that I presented today at Frontiers in TBI, we looked at a newly developed tracer called flortaucipir. In a group of people many years-- on average, 32 years-- after a single, severe, traumatic brain injury.
NIKOS GORGORAPTIS: And we found that a proportion of these individuals have increased tau in the brain. Going further, we examined the relationship of traumatic axonal injury, which we could measure using advanced MRI imaging techniques, a approach called diffusion tensor imaging. And we found that within areas of axonal injury, there was increased flortaucipir signals-- so effectively, tau pathology.
NIKOS GORGORAPTIS: And also a tau pathology related to reduced fractional anisotropy or traumatic axonal injury within white matter pathways that were indirectly or directly connected to brain areas where we had increased tau signal.
Segment:2 What is the clinical importance of understanding tau pathology after traumatic brain injury?.
NIKOS GORGORAPTIS: It's an important field in many ways. So firstly, it can help in diagnosis and prognosis for a patient. So it can be used down the line-- and we're not there yet.
NIKOS GORGORAPTIS: It can be used as a diagnostic tool, a way for our patients to get answers about what's wrong with them and for them and their families to be able to plan for the future. Secondly, it can help scientists test hypotheses and find out why brain trauma and traumatic axonal injury might then, later on, link to tauopathy-- neurodegeneration. And in some way, we did that in our study, looking at links between traumatic axonal injury and tau PET.
NIKOS GORGORAPTIS: Then, thirdly, perhaps the most exciting potential use of this technology, is in treatment trials. And there's several anti-tau compounds now in Phase I trials. And being able to pick up tau pathology in the brain, even before symptoms are evident, is important in order to be able to include people in these trials that will be adequately powered. And then, we'll be able to use this tau imaging to measure the effects of candidate treatments.
NIKOS GORGORAPTIS: So eventually, hopefully, imaging techniques such as flortaucipir will lead or help in the development of treatments that can prevent neurodegeneration in this high-risk population.
Segment:3 What are the limitations of using molecular imaging, such as PET scans, as an assessment method after TBI? And what do you think needs to be done to overcome these challenges?.
NIKOS GORGORAPTIS: It's a challenging population, and it's a challenging imaging modality to work with. So PET imaging, positron emission tomography imaging, in this population, has added challenges when compared to other neurodegenerative diseases.
NIKOS GORGORAPTIS: Because in severe, traumatic brain injury, we often have focal lesions that reduce our ability to pick up underlying regenerative pathology. But we were able to, to some extent, overcome these limitations by modeling for collisions carefully, statistically within our analysis. Secondly, the PET traces themselves, have their limitations. Although the current PET traces available represent an improvement on previously developed ones-- they bind in a stronger way to tau protein, for example.
NIKOS GORGORAPTIS: They're more selective for it. We're still probably not there yet in terms of the development of the ideal tracer. So for example, flortaucipir that we use doesn't just bind tau. It is known to bind on other molecules that are present in specific areas of the brain. We had to account for that in our analysis, which still produced informative results.
Segment:4 What is your favourite aspect of your research?.
NIKOS GORGORAPTIS: To some extent, we validated flortaucipir use in individuals with traumatic brain injury. But we went further than that. And we tried to answer questions about, why do people with traumatic brain injury get tau? Or, how does the hallmark pathology that's caused by traumatic brain injury-- that's traumatic axonal injury-- relate to tau?
NIKOS GORGORAPTIS: And we found that it does relate, and there is high flortaucipir signal within the immediate vicinity of tracts that have been damaged and show evidence of traumatic axonal injury and also within remote but connected areas. So we didn't just validate a technique that, down the line, may have some clinical use. We're also able to say something about the mechanisms of tauopathy, or neurodegeneration in traumatic brain injury.
Segment:5 Lastly, what predictions do you have for the future of this field?.
NIKOS GORGORAPTIS: Well, I think the future is very hopeful. We've got multiple compounds that are currently in Phase I trials, targeting tau, which could be using this high-risk population, possibly guided by PET imaging. So we may come up with treatments in the foreseeable future that might prevent the development of neurodegeneration and dementia for these people.
NIKOS GORGORAPTIS: And also tau imaging can help us understand the mechanisms. Like, how does mechanical injury or a traumatic injury to the brain lead to neurodegeneration later on? And this can also generate ideas for new treatments. [MUSIC PLAYING]
