University of Calgary-led international study shows promising results for neuroprotection by combining endovascular therapy with nerinetide
Kelly Johnston, Cumming School of Medicine
After 50 years of research and the testing of more than 1,000 drugs, there is new hope for preserving brain cells for a time after stroke. Treating acute ischemic stroke patients with an experimental neuroprotective drug, combined with a surgical procedure to remove the clot, improves outcomes as shown by clinical trial results published today in The Lancet.
The multi-centre, double-blinded, randomized trial, led by a team at the University of Calgary’s Cumming School of Medicine (CSM), Hotchkiss Brain Institute, and Alberta Health Services investigates the use of the neuroprotective drug nerinetide, developed by NoNO Inc, in two scenarios in the same trial. In one scenario, nerinetide is given to patients in addition to the clot-busting drug alteplase. In the second scenario, patients who were not suitable for alteplase received only nerinetide. Both groups of patients had concurrent endovascular treatment (EVT) to remove the clot.
“Compared to placebo, almost 20 per cent more patients who received nerinetide along with endovascular treatment, but did not receive alteplase, recovered from a devastating stroke – a difference between paralysis and walking out of the hospital,” says Dr. Michael Hill, MD, a neurologist at Foothills Medical Centre (FMC) and professor in the departments of Clinical Neurosciences and Radiology at the CSM. “In the patients who received both drugs, the alteplase negated the benefits of the nerinetide.”
Hill says the study provides evidence of a biological pathway that protects brain cells from dying when they are deprived of blood flow. Nerinetide targets the final stage of the brain cell’s life by stopping the production of nitric oxide within the cell.
“We really believe this is a new scientific observation,” says Hill. “There is evidence nerinetide promotes brain cell survival, offering neuroprotection until we can extract the clot. It opens the door to a new way of treating stroke.”
Images of patients’ brains from the study show the expected size of the damage from the stroke is sizeably reduced when nerinetide is administered and EVT is performed among patients not concurrently receiving alteplase.
Potential for a new tool to promote stroke recovery
“After so many studies investigating neuroprotective drugs failed, we are extremely excited by these results,” says Dr. Mayank Goyal, MD, PhD, a neuroradiologist at the FMC, and clinical professor in the Department of Radiology at the CSM. “While nerinetide is not approved for use yet, it shows the potential of a new tool to promote recovery from stroke.”
Worldwide, 15 million people suffer a stroke each year — that’s one every nine minutes in Canada and every 90 seconds in the United States. The results can be devastating. Ischemic stroke, the most common, is caused by a clot in a blood vessel in the brain. The sudden loss of blood flow causes brain cells to die, which can permanently affect speech, vision, balance and movement.
The international trial enrolled 1,105 patients between March 2017 and August 2019 at centres in North America, Europe, Australia, and Asia — a global academic collaboration bringing together scientists, clinicians, funding agencies, and industry.
“The collaboration between NoNO Inc., the University of Calgary and investigators at 48 leading stroke hospitals around the world has shown how effective such an academic-industry partnership can be in running high-quality, foundational stroke trials that can lead to positive changes in clinical practice,” says Dr. Michael Tymianski, MD, PhD, and CEO of NoNO Inc., the inventor of nerinetide.
The results in the current study, called the ESCAPE-NA1 Trial, build on the success of the ESCAPE trial, in which the Calgary Stroke Program proved that a clot retrieval procedure known as EVT can dramatically improve patient outcomes after an acute ischemic stroke. During the procedure, a catheter is inserted in the groin and guided through blood vessels into the brain. A tiny metal mesh device is used to grab the clot and pull it out. The current study investigates whether administering nerinetide in addition to clot retrieval improves the patient’s ability to recover.
The study is supported by the Canadian Institutes of Health Research (CIHR), Alberta Innovates, and NoNO Inc.
Dr. Hill is a member of the scientific advisory board for NoNO Inc. It is an unpaid position and he receives no financial benefit from the results.
Led by the Hotchkiss Brain Institute, Brain and Mental Health is one of six research strategies guiding the University of Calgary in its Eyes High strategic direction. The strategy provides a unifying direction for brain and mental health research at the university and positions researchers to unlock new discoveries and treatments for brain health in our community.
Dr. Michael Hill, MD, is a neurologist at the Foothills Medical Centre and a professor in the Cumming School of Medicine’s departments of Clinical Neurosciences, Radiology, Medicine, and Community Health Sciences and a member of the Hotchkiss Brain Institute, the Libin Cardiovascular Institute of Alberta and the O’Brien Institute for Public Health at the University of Calgary.
Dr. Mayank Goyal, MD, PhD, is a neuroradiologist at the Foothills Medical Centre, and EFW Radiology, a clinical professor in the Department of Radiology at the CSM and a member of the Hotchkiss Brain Institute at the University of Calgary.
About the University
The University of Calgary is a global intellectual hub located in Canada’s most enterprising city. In our spirited, high-quality learning environment, students thrive in programs made rich by research, hands-on experiences and entrepreneurial thinking. Our strategy drives us to be recognized as one of Canada’s top five research universities, engaging the communities we both serve and lead. This strategy is called Eyes High, inspired by the university’s Gaelic motto, which translates as ‘I will lift up my eyes.’
About the Cumming School of Medicine
The University of Calgary’s Cumming School of Medicine (CSM) is driven to create the future of health. We are a proud leader with seven world-class research institutes and 2,900 students, as well as faculty and staff, working to advance education and research in precision medicine and precision public health, improving lives in our community and around the world.
We are named in honour of UCalgary alumnus Geoffrey Cumming, who provided the largest single philanthropic gift in the university’s history in 2014. The CSM marked its golden anniversary in 2017, celebrating 50 years since our doors opened. Visit cumming.ucalgary.ca and follow us @UCalgaryMed.
About the Hotchkiss Brain Institute
The Hotchkiss Brain Institute at the University of Calgary consists of more than 120 scientists and clinician-scientists who are dedicated to advancing brain and mental health research and education. The Institute’s research strengths, in the areas of Brain and Behaviour, Neural Injury and Repair, and Healthy Brain Aging, are leading to new treatments for neurological and psychiatric disorders, aimed at improving quality of life and patient care. More information on the HBI can be found at hbi.ucalgary.ca.
About NoNO Inc.
NoNO Inc. is an Ontario biotechnology company whose focus is on developing therapeutic drugs in areas of unmet medical needs. Its drug pipeline includes therapeutic agents in various stages of development ranging from cellular and molecular discovery to human clinical trials. Its lead projects relate to diseases of the nervous system whose mechanisms involve the protein PSD-95, including stroke, traumatic brain injury and neuropathic pain. NoNO Inc.’s strategy is to inhibit key protein-protein interactions of PSD-95 that are involved selectively in cellular signals that cause cell damage, but without interfering with normal cell functions. For more information, please visit NoNO Inc.