Development of a protein tyrosine kinase inhibitor for modification of GAG chains and prevention of atherosclerosis

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/418934

Funding Status
Closed

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Funded Activity Summary

The major health issue in Australia is vascular and cardiovascular disease resulting from obesity and diabetes. Whilst prevention strategies based on lifestyle changes are preferable, treating cardiovascular risk factors with the latest drugs has been shown to produce significant benefits. There is however a large group of patients who still acquire cardiovascular disease in spite of drug therapy. New therapies are required and these will most likely target blood vessels directly. We have identified a biochemical mechanism that represents a prime target for vascular wall directed therapy and we aim to exploit the therapeutic potential of this pathway by developing a drug to prevent atherosclerosis. A group of large molecules which have recently received increasing attention are the proteoglycans, combined protein-sugar molecules which are heavily coated with negatively charged groups. The binding and retention of lipids in the wall of the blood vessel is the main cause of atherosclerosis. Specifically, the length of the sugar (GAG) chains on the proteoglycans determines the binding of the lipids. We have discovered a new class of inhibitors which directly target proteoglycan synthesis in the vessel wall and greatly reduce the interaction between proteoglycans and lipids. We wish to demonstrate the efficacy of our compound in an animal model with the aim to produce a marked reduction in the rate and extent of development of atherosclerosis. This would lay the foundation for the compound to be taken into human safety trials and subsequently develop an agent for the prevention of atherosclerosis and a thus a reduction in cardiovascular disease.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2008

Funding Scheme: NHMRC Development Grants

Funding Amount: $389,778.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Pharmacology and Pharmaceutical Sciences

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

atherosclerosis | cardiovascular disease | diabetes complications | drug development | drug discovery | lipoproteins | protein tyrosine kinase | proteoglycans | therapeutic target

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