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Inflammation plays an important role in heart attack, myocarditis, atherosclerosis and stroke, and is driven by chemokines, which recruit white blood cells to injured tissues. Unfortunately, sometimes the white blood cells start attacking healthy tissues and organs. It has not been possible to invent drugs that block the chemokine network in inflammation. Ticks, however, have evolved proteins in their saliva called evasins that block chemokines and inflammation very effectively. Prof Bhattacharya and his team have invented a technology, "Bug-to-Drug", which allows them to very quickly identify new evasins from tick saliva gland genes by inserting them into yeast. They have identified over 30 new evasins from different tick species, and have shown that they precisely bind certain subclasses of chemokines.
The team will develop evasins as precision treatments for inflammation, so that they hit only those chemokines relevant to a particular inflammatory heart disease and understand how these evasins work. We will study some of the new evasins in models of myocarditis, a deadly disease that leads to heart failure, and for which there is no effective treatment.
The team recently published new results in Scientific Reports on their genetically engineered evasins. They 'synthetically created the most effective of evasins from two different tick species and genetically fused them to create a preliminary drug that successfully prevented inflammation in laboratory tests'.
Speaking to The I Paper about the recent results, Prof Bhattacharya said “We’re really excited about this. This is a new class of potential drug which can target 80 to 90 per cent of the inflammation-causing chemicals produced by the body in diseases such as arthritis, pancreatitis, colitis and Crohn’s disease.”
This work builds on an RDM pump Priming Award to Prof Bhattacharya and Associate Prof Adam Mead. The work has gone on to leverage £1.8m funding.
“These little creatures could hold the secret to new treatments for a wide range of heart and circulatory diseases caused by inflammation,” said Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation. “This is an exciting new approach which could ultimately save lives,” he added.
Read ‘Genetically engineered two-warhead evasins provide a method to achieve precision targeting of disease-relevant chemokine subsets’ in Scientific Reports online here.