Systemic Therapeutics Uncovers the Protective Mechanism of Caffeine Against Cardiovascular Disease

February 09, 2022 3:43 PM EST | Source: Systemic Therapeutics Corp.

Hamilton, Ontario--(Newsfile Corp. - February 9, 2022) - Scientists from Systemic Therapeutics Corp. (the "Company" or "SystemicTx") have a new understanding of the protective effects of caffeine on the cardiovascular system. While its stimulant effects have long been characterized, a team of Canadian researchers have discovered how caffeine interacts with key cellular factors to remove cholesterol from the bloodstream.

In a landmark study published in Nature Communications, researchers have discovered that caffeine is responsible for triggering a cascade effect that reduces LDL cholesterol in the blood - the so-called "bad" cholesterol. Elevated levels of LDL cholesterol are associated with increased risk of cardiovascular disease.

The study team was led by Richard Austin, Executive Chairman and Chief Scientific Officer of SystemicTx, professor in the Department of Medicine at McMaster University and scientist at the Hamilton Centre for Kidney Research at The Research Institute of St. Joe's Hamilton.

They found that caffeine consumption was linked to a decrease in blood PCSK9 levels. PCSK9 is a protein that reduces the liver's ability to process excess LDL cholesterol. In the absence of PCSK9, more LDL cholesterol can be quickly removed from the bloodstream by the liver.

"These findings now provide the underlying mechanism by which caffeine and its derivatives can mitigate the levels of blood PCSK9 and thereby reduce the risk of cardiovascular disease," said Austin, senior author of the study.

Specifically, caffeine and its derivatives were shown to block the activation of a protein called SREBP2, which otherwise increases liver PCSK9 expression and its transport into the bloodstream.

"Given that SREBP2 is implicated in a host of cardiometabolic diseases, such as diabetes and fatty liver disease, these findings may have far reaching implications," added Austin.

This molecular domino effect is like a phenomenon previously described by Austin and colleagues. In 2020, they discovered how a rare genetic variant in the PCSK9 gene - one that reduces the secretion of PCSK9 from the liver - led to lower cholesterol levels and longer lifespans for those carrying this variant.

The interdisciplinary team included researchers from several McMaster University departments as well as the Libin Cardiovascular Institute of Alberta at the University of Calgary, Clinical Research Institute of Montreal affiliated with the University of Montreal, and Systemic Therapeutics, a pre-clinical stage biotechnology company, specialized in the development of new therapies for metabolic disorders.

Working with study co-author, medicinal chemist and Vice President of Drug Discovery at Systemic Therapeutics, Jakob Magolan, the team has developed novel caffeine derivatives that may lower blood levels of PCSK9 with much greater potency than caffeine, opening the possibility of developing new medicines to reduce LDL cholesterol.

"Our chemistry team and I are excited to be developing this new class of promising compounds for the potential treatment and prevention of cardiovascular disease," said Magolan.

About Systemic Therapeutics Corp.

Systemic Therapeutics Corp. is a pre-clinical stage, biotechnology company specialized in the development of new therapies focusing on the master regulators of lipid metabolism, the sterol regulatory-element binding proteins (SREBP), based on first-in-class SREBP inhibitors. The Company aims to provide new treatment options that improve the lives of patients affected by metabolic conditions such as dyslipidemia and Non-Alcoholic Steatohepatitis (NASH).

Corporate Communications:

Fady Hannah-Shmouni, MD DABIM FRCPC
Co-Founder and Chief Executive Officer
Systemic Therapeutics Corp.
Tel: (647) 673-3816

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