Dr. Michael Tymianski is developing a breakthrough drug that could slow a stroke's progression.Thomas Bollmann
Dr. Michael Tymianski is less than a year away from what could be one of the biggest medical breakthroughs in stroke treatment. The senior scientist at the Krembil Brain Institute, and his team, have developed a drug that could “allow the brain to hold its breath,” halting or slowing the progression of a stroke, so a patient can get to the right hospital for life-saving treatment.
This peptide drug, a small chain of amino acids with the name NA-1, is the result of more than two decades of work for Dr. Tymianski, who has two large-scale clinical trials currently underway. “Around the world, 17 million people have a new stroke each year, so the potential to help millions of people is there with a drug like this,” says Dr. Tymianski, who holds the Harold and Esther Halpern Chair in Neurosurgical Stroke Research.
Though doctors have made great strides in stroke treatment over the last two decades, there is still a huge amount of room for improvement. Presently, only 10 per cent of stroke patients return to their life as it was before their stroke, explains Dr. Tymianski, meaning that 90 per cent of stroke patients either die or have a lasting disability. This drug, developed at Krembil, could change those odds.
Improving outcomes
Currently, there are two main treatments for stroke.
The first is a clot-busting medication called tPA, which can dissolve smaller blood clots that prevent blood from flowing to parts of the brain. However, tPA has limits. It has to be administered quickly, within four-and-a-half hours of symptom onset, and can only be used for some types of strokes. It also causes brain hemorrhage in 7 per cent of patients, says Dr. Tymianski.
The second treatment is called endovascular thrombectomy (EVT). Here, doctors insert a catheter in the patient and thread it through arteries, all the way to the brain, to effectively grab and remove a blood clot.
Neither option is any good if a patient can’t get to a hospital before they experience extensive brain damage, and not just any medical facility will do. EVT is only available at large, urban hospitals.
Dr. Tymianski’s peptide drug, which is given through a single intravenous infusion, doesn’t replace tPA or EVT, but it could extend the treatment window. “The more time that goes by, the less likely it is that there will still be salvageable brain at the time the treatment is given,” says Dr. Tymianski. “If you can extend the window of opportunity for restoring blood-flow for patients, they do much better.”
The potential to essentially buy patients more time caught the attention of Heart & Stroke Canada, which funded Dr. Tymianski’s research with a grant in 2016. “The impact of stroke can be devastating, and the time frame for treating it is extremely short,” says Patrice Lindsay, director of systems change and stroke program for Heart & Stroke Canada. “Dr. Tymianski’s agent may be the first drug in history to demonstrate the potential to reduce stroke damage caused in patients. This holds great promise for stroke care in Canada.”
From lab to patient
Discovering game-changing drugs is a must, especially when it comes to the brain, where there aren’t easy ways to treat diseases and disorders. Krembil is trying to help more of its researchers get to the clinical trial stage through its Centre for Medicinal Chemistry and Drug Discovery (CMCDD), which was founded in August 2017.
The Centre, headed by Dr. Mark Reed, helps researchers translate their discoveries into drugs or procedures that can, potentially, be used to treat patients. “We can help academic researchers translate their work from basic discoveries – most of their time and energy is focused on advancing their field and then publishing their breakthrough discoveries – and see if there is a way we can take it forward into potential therapies,” says Dr. Reed.
One way the CMCDD helps is by employing on-site medicinal chemists – scientists who design drugs. These medicinal chemists use research produced at Krembil to try to develop small molecule therapeutics, a drug taken in pill form, which could be used in clinical trials down the road. “The Holy Grail is to make a pill that people can swallow once per day,” says Dr. Reed.
Dr. Reed, who has expertise in both business and science, also helps connect Krembil researchers to outside funding or industry partners.
One early success story is the work of senior scientist and glaucoma researcher Dr. Jeremy Sivak. In collaboration with Dr. Reed, Dr. Sivak received funding from LAB150, a partnership between MaRS Innovation and Evotec AG, a German pharmaceutical company, to accelerate drug discovery. It’s only the second LAB150 project to be awarded.
The funding has allowed Dr. Reed to hire two chemists to work on a potential new treatment for the degenerative eye disease, which is the leading cause of permanent blindness.
“As soon as you diagnose glaucoma, this treatment could, potentially, halt it in its path,” says Dr. Reed. “We are delighted to be working closely with Dr. Sivak to help translate his work and discoveries into meaningful therapeutics for patients.”
Trial results
While Dr. Sivak’s glaucoma research could be years away from a clinical trial, Dr. Tymianski’s research is its second year of trials.
He’s currently conducting two trials, one where Canadian stroke patients are administered the NA-1 peptide in ambulances, and another where patients are given NA-1 before they undergo endovascular thrombectomy. The latter trial includes 11,020 patients in Canada, the United States, Sweden, Ireland, Germany, England, South Korea and Australia. He wants to see in which situation the drug is most effective – on the way to the hospital or in the hospital before surgery.
Dr. Tymianski expects clinical trial results in October 2019, with publication to follow shortly after. Until then, he admits there is some excitement on his team, but it is mostly business as usual as everyone waits for what could be groundbreaking results. “I’ve been at this project for 21 years, so I am a patient man,” says Dr. Tymianski. “Our job is to do it right, not to take any shortcuts, and ensure that what happens is only the result of whether or not the drug works.”
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