Dr. Scott Simon, an experienced neurosurgeon and the Director of the Division of Cerebrovascular Surgery at Penn State College of Medicine, has spent 20 years at the bedsides of aneurysm patients. It’s that experience that led him to want to do more than simply treat the after-effects of patients’ brain bleed, and a reason why he joined with a multi-functional team of experts at Penn State College of Medicine in one of the three research projects funded by The Bee Foundation in 2023 to explore new avenues to brain aneurysm treatment.

Dr. Simon collaborating with Dr. Dajiang Liu, Phd, a public health expert whose research into genetics and genomics involves understanding how the composition of our DNA contribute to disease risk, and Graduate Assistant Timothy Helmuth. Their research is focused on a specific aspect of aneurysm outcomes: the role of iron metabolism in patient recovery.

“When blood enters the brain, the iron that is part of red blood cells is spilled,” Simon explains, “and that iron immediately starts killing tissue.”  Some people have a particular gene, HFE H63D, that allows them to have more iron in their cells at any given time than people without that gene.  This means that their cells can handle iron faster and more effectively than patients without this genetic variant.  Research in related fields has shown that animals and patients with this variant have better outcomes after injuries to their brains.  So far this gene has not been studied in patients with subarachnoid hemorrhage (aSAH) or ruptured brain aneurysms.  Simon explains: “If we can demonstrate that patients with this gene have a better recovery after aSAH, then theoretically we could help all patients by upregulating every patient’s ability to get rid of the poisonous free iron.”

Drs. Simon and Liu plan to collaborate by examining large, international genetic databases that are maintained online.  Each patient in these databases has his or her entire genome, or all of his or her genes, recorded along with the diagnosis codes describing the patient’s medical conditions.  The team will pull out the patients with aSAH and see if those with HFE H63D have a better outcome.  Patients could have many other factors affecting outcome, so pinpointing the effect of H63D will require large numbers of patients and advanced computational algorithms to parse out.  While the result of this investigation cannot prove a direct link between aSAH recovery and H63D, it can provide the sort of powerful pilot data that justifies further funding through NIH or NINDS StrokeNet.

The research is provocative.  If H63D in fact enables people to better handle higher levels of iron spilled into their brains following a brain bleed, Simon muses, could genetic therapy be administered quickly to ruptured aneurysms patients?  Would people with a family history of aSAH benefit from a vaccine?

Hopefully, this study will form the basis for others, mirroring TBF’s mission of turning pilot grants into big findings.