Modern medicine is a field of research that is constantly evolving, driving groundbreaking discoveries that have saved countless lives. Despite this growth, many serious medical conditions still lack effective treatments. Strokes, in particular, fall under this category and are a leading cause of temporary or permanent disabilities among Americans.
A hemorrhagic stroke occurs when a blood vessel ruptures, causing bleeding around and within the brain tissue, potentially leading to brain damage. Today, there is no effective drug available to treat this and patients have no other option than a high-risk surgical procedure to minimize the bleeding.
However, Dr. Ke Jian Liu, the associate director for basic science and a professor in the Stony Brook University Renaissance School of Medicine’s Department of Pathology, is pioneering research for a potential treatment by repurposing cancer drugs. Liu works alongside Dr. Rong Pan, a senior research scientist and a research assistant professor, who has collaborated on this project for the past eight years.
Dr. Liu said one of the primary goals in their research is to discover what is happening internally as people suffer a hemorrhagic stroke — specifically, what triggers brain injury and leads to the death of brain cells.
He emphasized that when researchers attempt to develop treatments to medical conditions, the process is extremely lengthy when producing an entirely new drug. By repurposing protein kinetic inhibitors, a treatment for various cancers such as leukemia and breast cancer, it speeds up the process since it is already approved for use by the Food and Drug Administration.
Their search for a potential treatment is now backed by a five-year, $2.6 million grant from the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health (NIH). Dr. Liu highlighted his excitement in receiving this grant to further the project’s research.
“[The] $2.6 million grant is for us to fully understand what is going on and try all the different protein kinase inhibitors that [are] currently on the market to see how it work[s] and what drugs works best,” he said.
Dr. Pan explained the effects of the bleeding from hemorrhagic strokes on the brain.
“After a hemorrhagic stroke, there’s blood in our brain, and around this area, the brain tissue has been pushed together,” Dr. Pan said. “[The blood] will release many [toxins] … Normally, our brain tissue has been protected by a barrier to limit anything going into the brain tissue, but when the blood goes into there, that means the protection is gone.”
She further explained that the harmful compound zinc protoporphyrin (ZnPP), which is produced through the action of ferrochelatase, an enzyme, plays a key role in brain cell death during a hemorrhagic stroke. Their research has shown promising results, demonstrating that using these inhibitors during a stroke can significantly reduce ZnPP levels, improve brain cell survival and preserve normal brain tissue structure.
Dr. Liu continued by discussing that brain damage from hemorrhagic strokes can vary, including in changes to neurological behavior. From the testing done on animal models’ brains, they have analyzed brain damage through numerous factors such as the amount of dead brain cells and blood vessel damages.
To compile this data, Dr. Changjian Feng, a professor in the Department of Pharmaceutical Sciences at the University of New Mexico, used mass spectrometry, an analytical technique to measure the data.
“To probe and analyze this [ZnPP] compound in animal models, they need special techniques to identify and quantify the small compound in brain tissue samples,” Dr. Feng said.
Dr. Feng further went into detail of different types of testing within mass spectrometry that were utilized in this particular project. Inductively coupled plasma mass spectrometry traces levels of metals and mass spectrometry imaging is used to gain insight on the spatial distribution of the ZnPP within the tissue samples.
“This information is key to understand the underlying damages caused by the hemorrhage,” he said. “It’s not just about the detection of this compound; you always want to quantify the change of the small compound because that’s related to the mechanism of the conditions [and] how this can cause damages.”
Dr. Liu discussed that the brain damage caused by these strokes can significantly alter a person’s life, affecting mobility, speech, memory and independence. However, with this treatment, Dr. Liu and Dr. Pan have a chance of developing a treatment that can reduce brain damage. Their animal models showed that those who received the treatment after a stroke were able to maintain better mobility and were left with minimal impact on their physical capabilities.
Even with these hopeful results, Dr. Liu and Dr. Pan believe that they have a long way to go with their research before attempting clinical trials on humans. Dr. Liu said that many questions remained unanswered and that NIH’s grant will give them the time and resources to explore them.
“What we want to do is move from initial observation into something that is firmly established so that people can believe in [this research] and view this as established evidence,” Dr. Liu said. “This work may provide the first treatment for strokes and that’s exciting.”
