On a quest to solve the biggest problem in stroke treatment

Urgency and disbelief merge in the voice of Shahid Nimjee, MD, PhD, when he shares that someone in America suffers a stroke every 40 seconds and only a small percentage of patients can be helped by medication or surgical intervention. He explains how the gravity of stroke gets watered down because post-stroke complications and secondary illnesses are what kill most stroke victims, not the stroke itself.

His voice gives way to heartbreak when he shares that the reason he has devoted his life's work to figuring out better treatment for stroke victims is because he lost his grandmother, who helped raise him, to a hemorrhagic stroke due to a ruptured brain aneurysm when he was 15.

“She is the reason that I do what I do for a living,” says Nimjee. “My grandmother and my parents have had such a huge impact on my life and my work.”

Nimjee is the product of what he says is the classic immigrant story. His parents, along with his grandmother, moved to Canada from east Africa three months before he was born so he and his siblings would benefit from greater opportunities and access to education. His father was a chemist, his mother a lawyer, and his grandmother, who grew up in South Africa and was a healer, had all the makings of being a doctor but never practiced due to issues with her vision. While his parents went back to school to earn new degrees in their fields after immigrating to Canada, they also worked to instill in their children a solid foundation of self-sacrifice and the ability to think about other people besides themselves. Nimjee learned from his family that in order to be good, one had to do good.

After completing MD and PhD programs, Nimjee began his neurosurgical training and cerebrovascular fellowship, spending evenings and weekends in the research lab working tirelessly to “do good” by stroke victims. His work has reached the threshold of bringing hope and healing to the 690,000 patients in the United States, and the 13 million people worldwide, who each year suffer acute ischemic stroke — stroke that is caused by a blockage, typically a blood clot, in the arteries supplying blood to the brain.

An area in medicine that could use some hope

Stroke ranks No. 1 in combined global illness and death. The reason physicians are only able to treat a minority of patients when a stroke occurs, between 3%-6%, is because there is only one drug treatment available — recombinant tissue plasminogen activator, or rTPA. It works by dissolving clots in blood vessels that lead to stroke, but its therapeutic window is short and not without risk as patients can develop a deadly hemorrhage in the brain after its use. What makes matters worse, only 10%-15% of stroke victims qualify for surgical removal of the clot.

“So basically, we have to tell eight of 10 people, ‘sorry, there is nothing we can do,’” says Nimjee.

“It’s those eight people who suffer disabling post-stroke complications and who often succumb to illness secondary to the stroke, that have kept me motivated to finding an alternative to rTPA.”

Learn more about the early warning signs of a stroke

Understanding how blood clots form

For Nimjee, an associate professor in the Department of Neurological Surgery at The Ohio State College of Medicine, his education began early on in medical school when he encountered patients whose lives were upended after a blood clot blocked or narrowed an artery leading to the brain, resulting in the brain not receiving enough oxygen, commonly known as an ischemic stroke. He saw firsthand how doctors did not have much in their arsenal to counteract the devastation brought on by these clots, whether in the brain, heart, lungs, arms or legs.

Motivated by the lack of treatment options at the bedside, he went to the research lab to try to find a solution. First, he worked to understand what happens on a cellular level when blood clots form. By understanding this, he hoped to learn how to prevent them from forming in the first place. He joined the research lab of Bruce Sullenger, PhD, a world-renowned nucleic acid biochemist and virologist who had just embarked on studying a new facet of RNA biochemistry that looked at aptamers.

The word aptamer stems from the Latin word aptus, which means “to fit” and meros, which means “part.” Aptamers are short, single-stranded DNA or RNA molecules that can selectively bind to a specific target, including proteins, peptides, carbohydrates, small molecules, toxins and even live cells. They bind because they “fit” their targets. Think of them as little hooks, like on Velcro. Once they attach, they prevent their targets from functioning. Another interesting aspect of aptamers is that they assume a variety of shapes due to their tendency to form helices and single-stranded loops. They are versatile, yet bind targets with high selectivity and specificity. Nimjee’s work looked to take advantage of aptamers in the treatment of strokes.