A new trial has shown for the first time that a drug may be able to slow the devastating damage that strokes can cause to the brain in some patients.

And the expanded window for treatment the Canadian-made medication seems to offer could mean the difference between paralysis or death and a functional, independent life, experts say.

“To my knowledge, this is the first time in the history of man that a trial has shown that (a brain-protecting drug) may improve the functional outcome of people with devastating strokes,” says Dr. Michael Tymianski, who created the compound and has been its staunch and often lonely champion for more than two decades.

“That is a real scientific milestone,” says Tymianski, a neurosurgeon and senior scientist at the Toronto Western Hospital’s Krembil Research Institute.

Tymianski announced the results of a clinical trial for his “neuroprotective” drug nerinetide — also known as NA-1 — at the International Stroke Conference in Los Angeles today.

The trial — the results of which were published simultaneously online by the journal The Lancet — showed the drug improved outcomes for some 20 per cent of patients when administered with a standard surgical procedure.

It’s “a difference between paralysis and walking out of the hospital” for the patients who responded to the drug, said University of Calgary neurologist Michael Hill, the lead co-ordinator of the international study.

“We really think we’ve shown something new here,” Hill says.

Conducted between March 2017 and August 2019, the trial involved 1,105 stroke patients who were all treated with a clot-removing surgical procedure known as endovascular thrombectomy or EVT.

Most strokes — some 87 per cent in North America — result from clots lodging in an artery within the brain, depriving the delicate neurological tissues surrounding the site of oxygen and nutrients.

In these so-called ischemic strokes, the blockages can rapidly lead to the demise of countless neurons in the region, causing paralysis, cognitive, speech and sight damage, and quite often, death.

Of the 15 million people who suffer strokes globally each year, almost six million will die, making them the biggest killer after heart disease, according to the WHO.

Some 13 per cent of these strokes, however, are caused by ruptured arteries — so-called hemorrhagic strokes for which the standard drug and surgical treatments used for the ischemic variety would be ineffectual or even lethal.

Thus, time must be taken to determine by brain scans which type of stroke has occurred. And in stroke, it’s said, time is brain — with damage cascading ruthlessly out from the blockage or vessel break as the minutes and hours tick by without treatment.

So for decades, a grail-like goal of stroke research has been to find a way to slow neuron death and damage until proper treatment can be administered. But in half a century of searching, not a single drug has been shown to produce such slowdowns, says Hill, who helped to pioneer the clot-busting EVT surgeries used in conjunction with the drug treatment during the trial.

As with many cardiac blockage surgeries, EVT uses a catheter inserted through an incision in the groin and snaked up to the brain through arterial routes. Yet, while the procedure has greatly advanced treatment in the past decade, strokes still leave 90 per cent of victims either dead or with significant neurological impairments, Tymianski says.

“So our drug is intended to help those patients by improving the ability of the brain to withstand the lack of blood flow until … restoration of blood flow can be achieved,” he says.

It does so by targeting the creation of the caustic chemical nitric oxide by brain cells in close proximity to the blockage. The drug “addresses a fundamental mechanism of brain-cell death that we discovered over 20 years ago,” Tymianski says.

That three-stage mechanism is triggered when cells are deprived of oxygen and produces the nitric oxide that goes on to kill other brain cells in a toxic chain reaction.

“Our drug breaks the middle link of that chain, thereby reducing or inhibiting the production of nitric oxide,” Tymianski explains.

He says neurons deprived of oxygen can “hold their breath” for a time, but are killed by the volatile nitric oxide while they are doing so.

“Our drug allows them to hold their breath a little longer,” he says.

Conducted in Canada, the U.S., Europe, Australia and South Korea, the study actually involved two drugs — Tymianski’s and the standard ischemic stroke medication tPA, which chemically helps bust up the clot.

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But as tPA quickly breaks down NA-1 in the body, no significant difference in post-treatment outcomes was detected for the 60 per cent of patients who received the clot buster. All study participants received either NA-1 or a placebo.

“In the 40 per cent of patients that did not receive tPA, our drug was very effective,” Tymianski says.

He says patients who were administered his drug in the absence of tPA saw mortality reduced by of 40 per cent over the placebo group and experienced about 20 per cent less brain damage around the blockage site.

“Almost 10 per cent more patients in the drug group reached functional independence as compared with placebo,” Tymianski says. “So that means that out of every hundred patients receiving the drug, 10 more would go back to living independently after having a devastating stroke,” he said.

On the whole, the study showed patients given NA-1 were 20 per cent more likely than those who received a placebo to be functionally independent after 90 days.

But Hill cautions that more work is needed, including another major trial, before the drug could be considered for approval from bodies like Health Canada and the U.S. Food and Drug Administration.

“Maybe we hit a double or a triple but we still have to bring that runner home.”

Tymianski says there is currently controversy among neurologists about the effectiveness of giving tPA to patients who also receive the clot-removing EVT surgery, which is remarkably good at clearing arteries on its own.

If it’s shown by several ongoing studies that giving tPA to patients who undergo the catheter operation is not necessary, it could greatly expand the pool of patients who might benefit from NA-1, he says.

He also says there are currently studies underway to see if giving patients with suspected stroke the drug in an ambulance en route to hospital can also reduce damage.

University of Calgary neurologist Dr. Mayank Goyal, another study author, says the drug might be particularly useful for patients who need to be transported long distances for surgical treatments.

But Tymianski’s struggle to get research on the drug funded — no major pharmaceutical company would pay — led him to create his own start-up called NoNo Inc. (The company name is a nod to NO, the chemical symbol for nitric oxide — so no NO.)

Tymianski has raised more than $120 million, tapping dozens of angel investors. Some of them are well known, such as Kevin O’Leary of “Dragons’ Den” and Josh Josephson of Josephson Opticians.

In the global world of neuroscience, Tymianski is something of an odd duck, doing extensive high-level work in brain chemistry while maintaining his practice as a top-flight neurosurgeon.

But Dr. Brad Wouters, head of science and research at the University Health Network, which takes in the Western, says most physicians there are encouraged to multi-task.

“UHN and the hospital are a little unusual in the fact that we make investments in research and hire scientists … that span that whole continuum from fundamental research all the way to treating patients,” Wouters says.