reports that one of the scorpion's toxins, margatoxin, is at least 100 times more potent at preventing neointimal hyperplasia - the most comon cause of bypass graft failure - than any other known compound.
Neointimal hyperplasia is the blood vessel's response to injury. It triggers the growth of new cells, causing chronic obstruction on the inside of the vessel.
When a vein is grafted onto the heart during a bypass procedure, the injury response kicks in as the vein tries to adapt to the new environment and different circulatory pressures. Whilst the growth of new cells helps to strengthen the vein, the internal cell growth restricts blood flow and ultimately causes the graft to fail.
The potency of the margatoxin in suppressing the injury response mechanism took the team by surprise, says lead author Professor Beech from the University's Faculty of Biological Sciences. "It's staggeringly potent. We're talking about needing very few molecules in order to obtain an effect."
The toxin works by inhibiting the activity of a specific potassium ion channel - a pore in the cell membrane that opens and closes in response to electrical signals and indirectly enhances delivery of a intracellular messenger, the calcium ion.
"We knew from experimental research in immunology that the ion channel Kv1.3 is involved in activating immune system responses and that it's linked with chronic inflammation problems in the immune system, such as those you see with multiple sclerosis," says Professor Beech. "Since our own studies had identified Kv1.3's presence in injured blood vessels, which are also often complicated by chronic inflammation, we wanted to see if the same immune system blockers would inhibit neointimal hyperplasia."
"There were a number of good blockers of this ion channel available to screen. Several compounds are developed from plants, and one comes from scorpion venom," he says, "but margatoxin was the most potent of all these compounds by a significant margin."
Professor Beech says margatoxin would probably be unsuitable as a drug that could be swallowed, inhaled or injected, but it could potentially be taken forward as a spray-on treatment to the vein itself once it's been removed and is waiting to be grafted onto the heart.
The research was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council.
Ioannis Delis, Physiological Society (Jul 2018), £10,000
Scott Bowen, Physiological Society (Jul 2018), £10,000
Steve Clapcote, Jamie Johnston, The Dunhill Medical Trust (Jun 2018), £254,874
Adrian Goldman, MRC (Jun 2018), £98,627
Darren Tomlinson, Michelle Peckham, Megan Wright, BBSRC (Jun 2018), £150,443
Simon Walker, Royal Society (Jun 2018), £337,601
Tom Thirkell, N8 Agrifood (Jun 2018), £14,870
Stephen Muench with Glaxo SmithKline & UCB Celltech, BBSRC Industrial Partnership Award (Apr 2018), £480,225
Steve Clapcote, BBSRC (Apr 2018), £443,072
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
Nikesh Patel, Medical Research Foundation fellowship (Apr 2018), £290,976
Graham Askew with colleagues in Hull and Liverpool, BBSRC (Apr 2018), £150,498
Andrew Macdonald, Neil Ranson & Richard Foster, Kidney Research UK (Apr 2018), £82,821
Jessica Kwok & Ralf Richter, Leverhulme Trust (Apr 2018), £298,273
Julie Aspden, Royal Society (Apr 2018), £20,000
Liz Duncan, Royal Society (Mar 2018), £14,602
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Stefan Kepinski & Netta Cohen, Leverhulme Trust (Feb 2018), £320,387
Lisa Collins, BBSRC (Feb 2018), £49,950
Alison Baker, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Lars Jeuken, BBSRC (Feb 2018), £30,000
Scott Bowen, Leducq Foundation Grant (Feb 2018), £28,470
Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
Dave Lewis and Colleagues in South Africa, HEFCE Global Challenge Research (Jan 2018), £48,000
Sarah Calaghan, Ed White, John Colyer, Isuru Jayasinghe, BHF (Jan 2018), £128,308
Christine Foyer and Alison Baker, HEFCE GCRF Grant (Jan 2018), £71,158
Alison Baker, Yun Yung Gong and Lindsay Stringer and ICRISAT India, HEFCE GCRF Grant (Jan 2018), £27,000
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Alison Dunn, NERC (Dec 2017), £18,000
Jennifer Tomlinson, Royal Society-Research Fellows Enhancement Award (Dec 2017), £94,681
Helen Miller, AB AGri Grant (Dec 2017), £73,600
Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
Ralf Richter, Royal Society (Dec 2017), £6,000
Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000