Scott Simon TBF Research Grant Update

Erin Kreszl, TBF Executive Director, catches up with Dr. Scott Simon on the outcome of the TBF Lora Beth Ritchie 2023 research grant: Impact of Genetic Variation in Iron Metabolism in Aneurysmal Subarachnoid Hemorrhage Outcomes 

A little background. . ..

Dr. Scott Simon and his research team (James Connor, PhD; Dajliamg Liu, PhD; and Tomothy Helmuth, Graduate Assistant) were awarded  a grant from TBF to explore a specific aspect of subarachnoid hemorrhage outcomes: the role of iron metabolism in patient reactions and recovery. Normally,  iron in the blood is spilled into the brain and is poisonous causing the death and disability seen in brain bleeds of all typesBut the team hoped to replicate what they had seen in mice: that in fact, the presence of H63D (or HFE) gene, a variant that increases the level of iron in cells, is actually tied to an improved outcome of patients with ruptures. 

In other words, Increased exposure = decreased negative reactions. 

The two aims of the study were, first, to build a large human database of SAH (subarachnoid hemorrhage) patients to serve as the basis for the research. A simple cheek swab would determine the presence of the HFE gene which could be merged with the patient’s already recorded outcome.. The second aim was to create a SAH-specific algo rhythm which would further clarify the relationship between the gene and aneurysm outcomes. 

What we’ve learned so far. . .

Working with their internal databases, the team was able to build an algorhythm that showed a positive correlation between the presence of the gene and stroke outcomes for ICH (Intracranial hemmorrhage) patients. Simon points out that while there are similarities between ICH and SAH (subarachnoid) aneurysms – the primary focus for TBF – work is ongoing to enable more conclusions about the role of HFE and in SAH. 

How did our grant advance knowledge in the area of aneurysm treatment and rupture? TBF’s grant achieved several critical goals: 

1. Validation of the need for critical data. The work validated what many researchers have been saying for years. In short, says Simon: We need a national stroke genetic database!”  For this study in particular, as the HFE gene is present in about 20% of the white population, a sizable database is critical to the research. And for research into the area in general,  when you are looking to draw conclusions about the roles of genes in hemorrhagic outcomes, you need a much larger database than currently exists. His team will be working with some of their partner organizations to get more patients enrolled and genotyped in the future. 
2. Foundational Infrastructure. A key critical outcome was that as an initial positive result, the grant allowed them to set up the infrastructure to enable them to continue pursuing  this work with both their internal data management and sequencing processes. 
3. NIH exploratory grant application.  The team has submitted an R21 (exploratory research) application to NIH which will enable them to leverage existing technology to introduce beneficial genetic variants into people who lack that variant. 
4. Industry visibility. The team also recently presented the research at the CNS (Congress of Neurological Surgeons) conference in Houston Texas, elevating the visibility of the findings and The Bee Foundation. 

Could this grant ultimately result in a retroviral vaccine that would provide more beneficial outcomes for SAH patients? Only more research will answer that question.