New Therapeutic Approach To Treat Atherosclerosis Developed

Atherosclerosis is a chronic inflammatory condition of the arterial blood vessel wall. In this disease, soluble mediators like cytokines and chemokines are pivotal players that promote vascular inflammation. Despite promising clinical studies in the past, the development of anti-inflammatory therapeutics directed against such mediators that could prevent atherosclerosis has proven difficult. The study led by Technical University of Munich (TUM) is published in the journal Nature Communications.

To prevent atherosclerosis, heart attacks, strokes, rheumatoid arthritis and other inflammatory diseases, therapeutic strategies have mainly been based on antibodies and small molecule drugs. The research team have designed and chemically synthesized short chains of amino acids -peptides - that function like a minimized soluble chemokine receptor. These peptides can block atherosclerosis in animal models.

New Class Of Peptides Against Atherosclerosis

Chemokines can lead to the migration of immune cells in our bodies and they are the key players in inflammatory diseases like atherosclerosis. Hence, they are of great interest to biomedical researchers.

The researchers have designed and synthesized peptides that mimic certain chemokine receptors and are able to specifically inhibit chemokine mechanisms that promote atherosclerosis. On the other hand, chemokine mechanisms that control important physiological processes in the body are not affected - one could say they are ‘spared’.

Earlier studies have shown the effectiveness of therapeutics related to cytokines and chemokines but these drugs interfered with the effect of these mediators on atherosclerosis and also suppressed their beneficial effects like those related to the host defense against infections.

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Aphrodite Kapurniotu, Professor for Peptide Biochemistry at TUM said, “The mini-CXCR4 mimics we have developed are able to selectively differentiate between two different chemokines that target the same receptor - in this case between the atypical chemokine MIF and the classical chemokine CXCL12. This enables them to specifically block pathways underlying atherosclerosis. Peptide-based therapeutics are often considered less stable, as peptides may get rapidly degraded in the body by enzymes called proteases. However, we can apply various state-of-the-art approaches of peptide chemistry to improve the stability of peptides, for example by introducing unnatural amino acids into the peptide sequence”

Prof Jürgen Bernhagen from the Institute for Stroke and Dementia Research (ISD) at the LMU University Hospital said that the approach was validated only in an animal model of atherosclerosis but future clinical applications are possible particularly due to the fact that peptide-based therapeutics are substantially less expensive than antibodies.

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Therapeutic potential

The researchers said that the results give a proof-of-principle of their approach and these findings show that the concepts based on mini-chemokine-receptor mimics are feasible and suggest that this kind of concept could potentially be applied to other chemokines as well.

This new molecular concept bears therapeutic potential for atherosclerosis and other inflammatory diseases.

Source-Medindia