We have awarded the 2018 Brain Aneurysm Research Grant to researcher, Ben A. Strickland MD, a 4th-year resident at the University of Southern California. We recently spoke with Dr. Strickland to learn more about his research project.
Tell us a little about yourself.
I am a 4th year resident at the University of Southern California. I was born and raised in South Carolina, went to college at Clemson where I double majored in Economics and Biology. I went to medical school at Baylor College of Medicine in Houston. My father is a general surgeon, mother was a kindergarten teacher before becoming a stay at home mom. I have one sibling, a brother one year older who is a family medicine doc. The whole family remains in South Carolina. I plan on pursuing a career in Vascular and Skull base Neurosurgery after I graduate. My main career interests include cerebral aneurysms, stroke, and cerebral revascularization. In my free time I am an avid sports fan of the Atlanta Braves and Carolina Panthers, but spend most of my off time being a beach bum in Santa Monica.
Why did you get involved in the field of brain aneurysm research?
Early in my residency I I realized brain aneurysm patients were among the sickest in the hospital and needed the most help. I felt particularly drawn to aneurysm patients due to the acuity… these declines were not gradual. These patients’ lives were changed un-expectantly in such a rapid manner, and it happens more commonly than most realize. I felt I could help make a difference in the field of cerebral aneurysms and give these patients their lives back.
What is the name of the research project for which you received the grant?
Title: Minocycline and Novel MRI Blood-Brain Barrier Permeability Analysis: Towards Early Detection and Treatment of Vasospasm Following Subarachnoid Hemorrhage
Can you give us a high-level overview of what you’ll be studying?
This study comes into play for someone that has had a brain aneurysm that has just ruptured. Even with a perfect surgery to treat an aneurysm, there is still a potential for a poor outcome. One of the biggest driving factors in a poor outcome is the development of a stroke in the following weeks. The strokes usually develop from a condition called a vasospasm, which occurs because the blood vessels are irritated by the bleeding from an aneurysm. We currently don’t have a great way to predict who will develop vasospasms, as we rely on crude and often unreliable methods. We also do not have many specific treatments for the vasospasm. We have recently developed a promising type of imaging study that helps us better predict which patients are most at risk for vasospasm. We now want to get a pilot study off of the ground to potentially treat the vasospasm before it causes a stroke.
What is vasospasm?
Vasospasm occurs as the result of an inflammatory reaction when an irritated blood vessel starts to contract in response to a ruptured aneurysm. The blood vessel becomes surrounded by the blood from the ruptured aneurysm and is also affected by the inflammatory response. Ultimately, the blood vessels contract meaning less blood flows to the brain, leading to the development of strokes.
How will your research impact the landscape of preventive brain aneurysm research?
It will hopefully prevent a major driving factor in a poor outcome of someone who experiences a ruptured aneurysm.
What are your ideal outcomes?
To find a way to effectively predict and treat vasospasm in aneurysm patients, thus preventing the development of stroke and death.
Assuming successful outcomes, what is the next step to advance your research?
If we find that minocycline has an effect on vasospasm we would follow with a large clinical trial with varying dosages to find out who should get what dose and when. With this research grant we will look at and test 20 but after that, for the trial, it would be in the 100’s.
We have recently validated a novel type of imaging study to predict which patients are most at risk for vasospasm with the MRI permeability studies. This study is able to show the breakdown in a special barrier of the central nervous system that correlates with development and severity of vasospasm. We are also able to monitor the breakdown of this special barrier by measuring levels of a protein called MMP9. Our study drug, Minocycline, is an inhibitor of MMP9. We hope to see Minocycline blocking the effect of MMP9 in destroying the blood-brain barrier, which we will be able to observe and quantify on the MRI permeability studies. Clinically, this would imply that we will be able to observe Minocycline decreasing the incidence of stroke from vasospasm.
What is MMP9?
Mmp9 is a protein that exists in a special barrier of the central nervous system, the blood-brain barrier. It is a structural protein that aids in maintaining the integrity of BBB.
When an aneurysm ruptures the integrity of the protein is compromised, and we can correlate rising levels of MMP9 to severity and onset of vasospasm. Minocycline is not new and is used as an antibiotic but recently has been investigated for ischemic strokes or intracranial hemorrhage trials, though this will be the first time its role will be investigated to treat vasospasm in humans.
Multiple laboratories have already demonstrated that MMP9 levels rise with the onset of vasospasm in the ruptured aneurysm patients. In animal models, we have noted that minocycline lowers the levels of MMP9 and incidence of vasospasm. Ultimately, we hope to see the same effect in humans.
This permeability study is a cornerstone to our research because it allows us, for the first time, to objectively measure and quantify changes to the BBB as a result of vasospasm, but similarly will allow us to measure any therapeutic effect of minocycline in maintaining the integrity of the BBB.
With the recently published studies involving the relationship of vasospasm to MMP9 and minocycline, and the validation of the MRI perfusion studies, this is the right place and time to proceed with our proposed study. This is just a really exciting time to be in the field.
How will you choose the 20 who will be candidates for the use of this study?
This is a repurposed use for the drug which means it is already FDA approved. The patients will give signed consent and we must be able to see them within first 24 hours of a brain aneurysm rupturing.
Will this research branch out into other areas?
It is difficult to say, as this study is most relevant to the brain, however, vasospasm is resulting loss of blood flow is not a problem limited to the nervous system.
How would you explain this research study to a friend who does not conduct clinical research?
After an aneurysm ruptures and is treated and that patient has had surgery -you’re not out of the woods. There is a lot that can still happen one of those is a stroke of the brain. Our study is trying to take away the worst of those outcomes.
Are you excited to attend the Honey Bash?
Yes! Very excited! This year, Sept 29th will be my first Honey Bash.
What is one thing you want people to remember about your research?
To remind people that this is a very exciting time for brain aneurysm research and we have made significant strides. There is a very optimistic future and this stuff is in that genre of that excitement.
In 50 (or so) words or less, what would you like the world to know about brain aneurysms?
They are more common than most people realize and have likely already affected someone we know. Although we have made significant strides forward, there remain many areas that need improvement. But the future of the field is optimistic and we are not helpless against this disease.
What needs to be done to better educate people – primary care providers, as well as, those not in the medical field – about the risks and warning signs of brain aneurysms?
Unfortunately, we don’t know an aneurysm exists until it causes a problem in the majority of patients. An estimated 3-5% of us have one and we may not know it until something is wrong. So, most of the treatment is damage control. We’re in an exciting time in the field where we’re trying to be preemptive and we’re starting to get there. If someone is known to have a BA it should be followed closely.
How can people outside the medical field best support brain aneurysm awareness and research?
There are lots of venues to help raise awareness and get involved. A brain aneurysm could affect anyone of us. That is why it is so important to support foundations such as the Bee Foundation. We also have recently started a charity fundraiser partnering with the Los Angeles marathon with an aneurysm survivor group. We need more people to get involved. We are continuing to make progress to better treat these patients, and it will only get better with more awareness and resources devoted to the cause!
The 2017 Brain Aneurysm Research Grant went to two researchers, Jennifer Kim, a neurocritical care fellow at Mass General Hospital, and Justin Mascitelli, cerebrovascular fellow at the Barrow Neurological Institute in Phoenix.