Beat stroke damage through neuroprotection
Dr. Yu Tian Wang is working on drugs that could save your brain cells after a stroke
Chapter 1 Finding a purpose
Dr. Yu Tian Wang remembers how helpless he felt as a young medical intern working in the neurology department of the Shandong Medical University hospital in China. It was the early 1980s.
The patients included people with stroke and other kinds of brain disease and injury. “At that time in the neurological ward, we did not have any good way to treat them,” he says. “To see them suffer was hard.”
Those feelings sparked a sense of purpose that has driven him to this day.
“I realized we didn’t really understand how the brain functions normally, or how neurons (brain cells) become injured or damaged under diseased conditions.” He wanted to understand at the most basic level, and that meant heading for the lab.
Chapter 2 Defining the problem
Today Dr. Wang, a neuroscientist at the University of British Columbia, holds the Heart & Stroke BC & Yukon Chair in Stroke Research. He is a world leading expert on how brain cells die and how they can be rescued.
With support from Heart & Stroke donors over decades, he has systematically built a picture of the microscopic processes that work in our brains 24 hours a day. And he has shown how those processes are disrupted by stroke and other kinds of brain injury and disease.
The stakes are high for this work.
In most strokes, Dr. Wang explains, a clot blocks blood flow to part of the brain. “Neurons die very fast; 1.9 million will die within one minute after stroke.”
The more brain cells die, the more likely the person will die or be left with lasting disabilities — like the patients Dr. Wang saw in the neurology ward.
Before a stroke can be treated, it needs to be diagnosed. Is it ischemic, caused by a clot, or is it a rarer hemorrhagic stroke, in which bleeding results from a ruptured blood vessel? Ischemic strokes can be treated with clot-busting medication or a procedure to physically remove the clot (endovascular thrombectomy).
Specialized stroke teams in many hospitals move fast to get the patient diagnosed, using a CT scan or MRI. But even at its most efficient, this process uses precious minutes.
What if you could throw a chemical switch to slow or stop the cascade of brain cell death in the first minutes and hours after stroke? You could buy time to diagnose and treat the stroke, restoring blood flow to the affected areas of the brain.
That’s exactly the problem Dr. Wang and his collaborators are focused on.
Chapter 3 The promise of neuroprotectant drugs
A neuroprotectant is a drug or treatment that protects the neurons from damage or death. One that shows promise is NA-1, a peptide that blocks the release of a chemical called glutamate after a stroke.
Work by Dr. Wang and others had showed that an excess of glutamate is a key trigger for cell death after stroke. “It binds to the receptors on the cell surface, overexciting them and finally leading to cell death,” he says.
NA-1 was originally developed in Toronto by neurosurgeon Dr. Michael Tymianski, who also had Heart & Stroke funding. He called on Dr. Wang because he had developed a stroke animal model in the lab, and that was the next stage for testing the drug.
“We moved their research from a culture dish into a real live animal model,” says Dr. Wang. This was difficult work that involved simulating human-like strokes in mice. “At that time, our lab was one of the few that could do this.”
His team showed that if you give NA-1 even several hours after stroke in the animal models, it is still effective in reducing the injured area and saving neurons, resulting in better recovery.
Dr. Wang is excited by the results of NA-1 clinical trials at sites around the world, including combining NA-1 with mechanical removal of the clot. There is also a trial with paramedics administering the drug on the way to the hospital.
“This drug has no side effects because it is designed to break this cell death signal,” Dr. Wang says. “It won’t affect the normal functioning of the receptor. So you can give this drug anytime.”
Chapter 4 More pathways to protect brain cells
While NA-1 continues through clinical trials toward eventual release, Dr. Wang’s lab is working on other potential drugs that could help keep brain cells alive.
One project is developing a molecule that could activate a survival process within the cell that his team discovered — essentially, the opposite approach to NA-1.
“We can give this molecule independent of NA-1,” he says. “We could also combine it with NA-1 — so, on one side this would block cell death, and on the other side it would promote cell survival.”
Within 10 years, he believes, these will be just some of a growing range of neuroprotectant drugs that target various pathways, including inflammation and free radicals. And together they will complement improved clot-busting treatments to restore blood flow after an ischemic stroke.
Dr.Wang wants to beat stroke and the damage it causes.
To do it, he says, Heart & Stroke funding is critical. “Continuous support means the work continues step by step — as we worked on the cell death signal pathway, then those discoveries led to work on the cell survival pathway.”
An event that turned her universe upside down
How a few hours changed the life of a former Mrs. Universe Canada