We are honored to announce the recipients of the TBF 2024 Preventative Research Grant Cycle. This year’s grant cycle was very strong prompting J. Mocco, head of the SAB, to comment that only the number of proposals received, but their impressive quality, indicated that TBF was now a true catalyst for the kind of seminal work that could turn into breakthrough research and ultimately major NIH dollars.
Each of our research grants has been generously supported by a different family who has been touched by brain aneurysm and is dedicated to funding preventative research. This grant has been awarded by Yezzi Family. Zac Yezzi, survived a ruptured brain aneurysm and AVM in 2021 and his family has been dedicated to spreading awareness and funding research. Zac’s family and friends have raised over $175K and separately funded three research grants for brain aneurysm prevention. Zac shares “my outlook on life has changed dramatically—I’ve become extremely determined to do anything I can to pay it forward, including supporting The Bee Foundation’s work. I am honored to support Dr. Hale’s research and hope this moves us closer to preventing others from having to go through what I did.”
Principal Investigator: Andrew T. Hale, MD, PhD, Neurosurgery Resident, University of Alabama at Birmingham
Project: Identifying somatic mutations and transcriptional pathways in cerebral aneurysms using endoluminal biopsy
What We Liked: The project’s leveraging of new understandings and technologies used in other diseases provides new possibilities for detection and treatment of Intracranial Aneurysms (IAs) and AVMs, In addition to fitting with the TBFs stated goal of aneurysm prevention through innovation, the project also provides hope for more personalized care for affected individuals.
Recently, Erin interviewed Dr. Hale to get some additional information on their proposal.
Erin: Thanks for talking with us, Andrew! First, I know you got your PhD at Vanderbilt and are now doing your residency in Neurosurgery at the University of Alabama at Birmingham, but can you tell us what’s behind your interest in this field and specifically this research project?
Dr. Hale: Thank you very much for having me. I am honored to receive this grant and your support! The motivation of this grant is based on the hypothesis that aneurysms (and AVMs) don’t develop randomly without an underlying encoded genetic signal. Certainly it’s increasingly being acknowledged that multiple genes play a role in areas like aneurysms and AVMs, and we know that there are a number of genetic conditions that predispose a person to IAs. But many – probably most – IAs are not associated with these factors.
I believe there is a huge underappreciated genetic component here that indicates we need to look at this area differently. A basic premise of our study is that the cells within the IA itself differ from the cells around it and that there is something unique about those cells that causes the aneurysm to form. So understanding those cells, the mutations within them associated with IA formation, and the growth and replication pathways for those mutations, are critical. Most prior studies have not looked at these cells, but rather at what we call germline tissue (a cheek swab for instance). But we feel this approach is not giving us the answers we need – hence our focus on direct analysis of IA tissue in situ. Also – and this is the biggest nuance from the genetic side – a lot of people have analyzed 10 or 15 genes but that is already a biased view as you are looking at a set of genes that have already been identified as playing a role in IAs or AVMs. Our study is genome wide – we are looking at the whole genome with the idea that the mechanisms that might be causing the IAs might be more complex.
Erin: I know that getting to those cells inside the IA – and getting them into a lab for analysis – has been difficult, but your research improves on existing methods, with a quicker way to get the cells to the lab as well as the use of ETC (endoluminal tissue sampling).
Dr. Hale: Absolutely, developing technologies have given us a great chance to advance our abilities in these areas. As some background, most promising among the evolving endovascular approaches is the idea of a coil based biopsy (not to be confused with the coil used in treatment to prevent or contain a rupture). Here, a coil is introduced into the IA itself to extract the cells through endovascular surgery. The main problem is that it is very difficult to get the cells successfully from their location into a laboratory to be analyzed. First of all, any time you deploy a coil into an aneurysm or AVM it can fall out – it’s a known drawback. Also, it is very hard to predict how many cells you will get off the coil, and if you don’t get it to a lab quickly the cells you have can die. We have developed a technique that allows us to extract the coil to the lab within 30 minutes. Our use of ETS (endoluminal tissue sampling) – which is new here but has been validated in many other uses – allows us to examine many more cells than previously possible and generate better understanding.
Erin: I know that our SAB was also impressed with how your research was reflecting learnings that had been gained in other diseases.
Dr. Hale: That’s an important point. Our fundamental premise reflects basic premises in cancer research, where it has been established that cells developing from a cell with a mutation carry that same mutation. We have found that same pattern in AVM patients, which is good news as it means that those patients can benefit from protocols that are already FDA approved.
Erin: What patient population will you be using for the study?
Dr. Hale: We’ll be focusing on patients with multiple aneurysms or family history, but not patients with a known genetic predisposition as those would be less likely to yield new insights. We’ll also focus on younger patients who are less likely to have issues connected with aging that could impact aneurysm formation.
Erin: So in summary, what do you think are the most important outcomes of your study? Who would the research benefit, and how?
Dr. Hale: The end goal is to be able to identify a biological and genetic basis for an individual patient’s aneurysm and provide a better level of personal medicine. Put simply, if we know that a patient has a mutation in one of the critical cell pathways, we can counsel them more knowledgeably and effectively on potential treatments, primarily the kinds of medications that are currently being prescribed, some of which have potentially very serious effects.
