How Canadian research helped develop promising new cholesterol drugs
Published Thursday, March 16, 2017 10:21PM EDT
When the world’s leading cardiovascular experts gather in Washington, D.C. on Friday for a three-day conference, they will highlight a new class of cholesterol drugs developed thanks to an important Canadian discovery.
In 2003, Nabil Seidah, director of the biochemical neuroendocrinology lab at the Clinical Research Institute of Montreal, and a team of scientists discovered PCSK9.
It’s an enzyme encoded by a gene on chromosome 1, the largest human chromosome. PCSK9 is a powerful regulator of LDL, or bad cholesterol, in the blood. When PCSK9 is overactive, people can end up with dangerously high cholesterol. If it’s underactive, people have markedly low cholesterol, with a low risk of heart disease.
That discovery helped set off a flurry of research to find ways to block PCSK9, stopping cholesterol from accumulating in the arteries.
“You basically force nature to do its job and to clean the excess cholesterol,” Seidah told CTV News.
Cardiovascular disease is the leading cause of death in the world, and its development is intimately linked to elevated levels of cholesterol in the blood.
Doctors commonly prescribe statin drugs such as Lipitor and Zocor to help lower cholesterol in patients. Statins inhibit a liver enzyme involved in the production of bad cholesterol and help clear the body of it. But up to 20 per cent of patients can’t tolerate the side effects of statins, which include muscle pain and inflammation and even memory loss in some cases.
And in some patients, statins simply don’t lower cholesterol levels enough, which is why the PCSK9 discovery was celebrated in the scientific community.
In early studies, PCSK9 blockers were able to slash LDL cholesterol in patients with an inherited form of high cholesterol by more than 50 per cent, even when added to a maximum dose of statin drugs.
Seidah’s research led to an entirely new class of cholesterol-lowering drugs – PCSK9 inhibitors such as Repatha and Praulent – now available to high-risk patients with a family history of high cholesterol. Patients inject the drugs once or twice a month.
Some doctors studying the new drugs call the Canadian-discovery that started it all a breakthrough, especially for patients who haven’t seen good results with statins.
“I have patients who we struggled to get their cholesterol down for years, and we added this, and their cholesterol levels are now unbelievably low – lower than we ever expected,” said Dr. Larry Leiter, an endocrinologist and professor at the University of Toronto’s school of medicine.
Dr. Rob Hegele, an endocrinologist and distinguished professor at the University of Western Ontario, said Seidah has been instrumental in the development of PCSK9 inhibitors.
“Since 2003, Seidah has taken the ball and run with it – hundreds of papers on PCSK9 literally, including making the link with human cholesterol disorders,” Dr. Hegele told CTV News. “He’s certainly identified today with PCSK9, and is seen by most people as the sole architect of the molecule.”
Seidah came to Canada after studying at Cairo University in Egypt and getting his PhD in biophysics from Georgetown University in the U.S. But he says getting funding for his breakthrough research from Ottawa was a struggle. His applications to the Canadian Institutes of Health Research were repeatedly rejected, but he eventually persevered.
“You should never give up if you believe in what you do,” he said.
Some are even suggesting that Seidah should be nominated for a Nobel Prize for his research.
“I’m in it for the love of science,” Seidah said. “If we get the Nobel, good! If not, we are having fun anyway.”
On Friday, scientists at the American College of Cardiology’s annual expo will discuss larger studies of some PCKS9 inhibitors, measuring their ability to stop heart attacks and strokes and deaths from cardiovascular disease. Depending on the results, it could usher in wider use of these new medications.
With a report from CTV’s medical specialist Avis Favaro and producer Elizabeth St. Philip