Guelph, Ontario, Canada -- October 3,
2019 – A potential drug to treat heart attacks and to prevent heart failure – for
which no cure currently exists — may result from pioneering research by a
University of Guelph professor.
Prof. Tami Martino, Department of
Biomedical Sciences, and PhD student Cristine Reitz have discovered what they
believe is a novel drug target controlling the body’s repair responses after a
heart attack.
A leading cause of death worldwide,
heart attacks trigger inflammatory responses that cause a scar to form in the
heart. Over time, that damage eventually leads to incurable heart failure.
Administered within hours of an attack,
the potential drug would prevent scarring. It would also eliminate the need for
patients to take possibly debilitating heart medication for the rest of their
lives.
“This research is really exciting
because it opens the door to use circadian medicine therapies to heal heart
attacks after they occur and to prevent the subsequent development of heart
failure,” said Martino, a pioneer in circadian medicine.
The circadian “clock” is found in
virtually all cells of the body. It consists of genes and proteins that
interact during 24-hour day and night cycles to regulate key functions such as
heart rate and blood pressure.
In the heart, that clock mechanism
controls healthy cardiovascular physiology as well as how the heart responds to
damage and undergoes repair.
The researchers’ new paper was published
in Nature
Communications Biology. Martino’s lab will now begin preclinical trials
on a potential therapy.
The researchers used a drug called
SR9009, which targets a key component of the cellular clock mechanism. The
medication disrupts expression of genes that trigger adverse immune responses
after a heart attack.
In Martino’s experiments with mice, the
treatment reduced production of a cellular sensor called the NLRP3 inflammasome
that contributes to scarring. The U of G researchers showed for the first time
that giving this treatment after a heart attack along with conventional therapy
such as reperfusion led to less inflammation and better cardiac repair.
That allowed healing almost as though no
heart attack had happened, said Martino, who is director of U of G’s Centre for
Cardiovascular Investigations.
“No scar, no heart damage, no heart
failure – people can survive heart attacks because the heart won’t even be
damaged. We were amazed to see how quickly it worked, and how effective it was
at curing heart attacks and preventing heart failure in our mouse models of the
disease.”
The discovery might ultimately help in
other heart therapies involving early adverse inflammatory response such as
organ transplant or valve replacement, she added.
More generally, it may also help with
profound adverse inflammatory responses, such as treatment of traumatic brain
injury, strokes or severe burns, she said.
Funded by the Canadian Institutes of
Health Research, this study is part of her lab’s pioneering work on circadian
medicine. By studying how disruptions to body clock rhythms drive heart
diseases,
Martino aims to manipulate circadian biology with genetic,
environmental or pharmacological therapies.
“What we are discovering is that the
circadian clock mechanism is important not just for heart health
but also for
how to heal from heart disease,” said Martino, who is a mid-career investigator
of the Heart and Stroke Foundation of Canada.
“Circadian medicine is truly a promising
new field that will lead to longer, healthier lives.”
Her co-authors are former PhD student
Faisal Alibhai and current post-docs Tarak Khatua and Mina Rasouli. The team
collaborated with U of G pathobiology professor Byram Bridle and Thomas Burris,
a researcher at Washington University.
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