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.
- Photo above: Many of the team members of the Calgary Stroke Program. Photo by Roth & Ramberg
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.
