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Preventing and reversing accelerated atherosclerosis in patients with diabetes

University of New South Wales

Grant:
  • Cardiovascular Senior Researcher Grant
Organ System:
  • Cardiovascular
Date Funded:
  • 22 May, 2020
Chief Investigator/s:
  • Professor Kerry-Anne Rye

Project summary

Evaluate the capacity of a new peptide called C-II-a that mimics the cardioprotective properties of the main HDL apolipoprotein to reduce heart disease in people with diabetes.

What does the research aim to do and how?

Professor Kerry-Anne Rye (BSc (Hons), PhD, FAHA) is Head of Research at the School of Medical Sciences, University of New South Wales. She is recognised internationally for her work on high density lipoprotein (HDL), or “good cholesterol” structure and function, and was the first to report that HDL apolipoproteins have anti-diabetic and anti-inflammatory properties. Her research is concerned with understanding the roles of HDL apolipoproteins in preventing heart disease, which is increasingly recognised as a pro-inflammatory and pro-oxidant disease, and preventing diabetes, a disease that is driven by loss of insulin-producing cells in the pancreas. Professor Rye is actively involved in the development of new therapies for both disorders.

This project will evaluate the capacity of a new peptide called C-II-a that mimics the cardioprotective properties of the main HDL apolipoprotein, apoA-I, to reduce heart disease in people with diabetes. Professor Rye has already shown that C-II-a (i) inhibits inflammation in cells involved in heart disease and (ii) regenerates cells in the pancreas. This is a potential game changer for patients with diabetes, who are at high risk of developing heart disease.

The first part of the project asks whether with C-II-a, when used with an inhibitor of the pro-oxidant, pro-inflammatory enzyme myeloperoxidase (MPO), stops heart disease from developing and reverses established heart disease in established mouse models of diabetes. Heart disease will be induced in the animals with cutting-edge anti-sense oligonucleotide technology.

Existing, innovative, patent-protected technology for generating a form of C-II-a/MPO inhibitor that can be taken by mouth, rather than by injection, will also be developed further.

The final part of the project will identify the optimal timing for C-II-a/MPO inhibitor combination therapy in heart attack patients with and without diabetes.

Collectively, these studies will set the scene for the translation and commercialisation of combination C-II-a/MPO inhibitor therapy into a highly innovative and transformative treatment option for patients with diabetes and heart disease.