Ten years of collaboration have led to new drug candidates for cardiovascular disease

Cardiovascular disease is one of the leading causes of death worldwide. Since 2015, researchers in Örebro have been collaborating with researchers at the National Hellenic Research Foundation (NHRF) in Greece to identify new ways of preventing and treating these diseases.

So far, the collaboration has led to the identification of several new drug candidates, compounds that could potentially be developed into medicines in the future. The researchers have also gained new knowledge about how these compounds may reduce inflammation in blood vessels and prevent blood clot formation, two processes that play an important role in the development of cardiovascular disease.

“The drugs currently used to treat cardiovascular disease mainly target blood pressure, blood lipid levels, blood sugar levels and the prevention of blood clot formation. Several of the compounds we have investigated act as JAK and ROCK inhibitors respectively, two important signalling pathways involved in inflammation and blood clot formation. Some of the compounds we have studied even demonstrate a dual effect, acting on both inflammation and blood clot formation,” says Karin H Franzén, docent in biomedicine at Örebro University.

Better medicines could help reduce suffering

In the long term, the research may have implications for the treatment of patients.

“The development of more effective drugs could hopefully help reduce suffering for a large group of patients in the future,” says Karin H Franzén.

The collaboration with Greece began in 2016 after Maria Koufaki, research director and researcher in medicinal chemistry at the National Hellenic Research Foundation (NHRF), heard Karin H Franzén present research on inflammation and cardiovascular disease at a scientific conference in Athens.

Within the consortium, Maria Koufaki’s research group has been responsible for the design and synthesis of drug candidates, which the research groups of Karin H Franzén and Professor Magnus Grenegård at the Cardiovascular Research Centre (CVRC) in Örebro have investigated in various models of cardiovascular disease. Maria Zervou and staff at the NHRF have complemented the biological analyses with computer modelling of the compounds.

Contributing different areas of expertise

The consortium’s approach combines expertise from several disciplines. NHRF contributes knowledge in medicinal chemistry, while Örebro University provides expertise in the molecular evaluation of compounds, the biological mechanisms underlying cardiovascular disease, and the therapeutic potential of promising drug candidates.

However, the path from a promising laboratory compound to an approved drug is a long one.

“We have succeeded in clarifying the compounds’ mechanisms of action and have further developed the chemical methods used to produce even more potent variants. In addition, we have shown that the compounds protect heart muscle tissue from damage caused by oxygen and nutrient deprivation, meaning that they have the potential to be used to limit damage following a heart attack. At the same time, it should be emphasised that further development towards clinical trials in humans would require collaboration with an industrial partner in the pharmaceutical sector,” says Magnus Grenegård, professor of biomedicine at Örebro University.