By Heather Hobbs
BRINGING YOU THE LATEST NEWS & EVENTS FROM THE SCIENCE INDUSTRY Project to Fight AMR Backed by ERC Funding
A mission to help develop new types of antibiotics that can target and kill bacteria that are resistant to current antibiotics, led by Queen’s University Belfast (QUB) researcher Dr Stephen Cochrane, has received a European Research Council Award of €1.5 million. It is the twelfth ERC award given to a QUB academic since the scheme opened in 2007. The project will run for five years and will be supported by five early career researchers.
Dr Cochrane, School of Chemistry and Chemical Engineering at QUB explained: “Almost all of our antibiotics work by crossing the cell membrane to get inside the cell and once they are inside, they disrupt an essential process, which then kills the cell. The problem is that many compounds can’t cross the cell membrane and for those that do get inside, the cell can neutralise their effect, rendering them useless.”
The aim of Dr Cochrane’s team will be to create new chemical tools that will enable the discovery and development of antibiotics capable of destroying the harmful bacteria.
“Antimicrobial resistance (AMR) is one of the greatest challenges to human health. If it continues to develop at the
current rate, the negative impact on global health and the economy could be much worse than the impact of Covid-19.”
“To combat AMR, we need to develop new antibiotics. In the past 60 years only five new classes of antibiotics have been approved for clinical use. A major hurdle in antibiotic discovery is finding antibiotics that can cross the cell membrane and overcome the resistance mechanisms of these cells.
“My project ‘NEW HOPE’ offers a new approach to antibiotic discovery. Instead of looking for targets inside the cell, I’ll focus on cell-surface targets. To do this, my team will use the tools of synthetic organic chemistry and molecular biology to develop new tools for antimicrobial discovery and unlock novel antibiotics.”
President of the European Research Council, Professor Maria Leptin said: “It is a pleasure to see this new group of bright minds at the start of their careers, set to take their research to new heights. I cannot emphasise enough that Europe as a whole - both at national and at EU level - has to continue to back and empower its promising talent. We must encourage young researchers who are led by sheer curiosity to go after their most ambitious scientific ideas. Investing in them and their frontier research is investing in our future.”
Stephen Cochrane (Credit: QUB)
Dr Cochrane added: “I’m hugely honoured to have been awarded an ERC Starting Grant. I’m very thankful to my amazing mentors and colleagues for the help and support they provided during this journey. I look forward to building a new research team and tackling such an important global challenge.”
More information online:
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Trial Raises Hope for Treatment of Strokes Linked to Dementia
A clinical trial led by researchers at the University of Nottingham and the University of Edinburgh have indicated the potential of two common drugs to be repurposed for the first specific treatment for people who experience a type of stroke linked to nearly half of all dementias.
Funded by the British Heart Foundation, the trial has shown that isosorbide mononitrate and cilostazol, already used to treat other heart and circulatory diseases and particularly used in combination, can safely and effectively improve the debilitating outcomes people experience after lacunar stroke, including problems with thinking and memory, movement and even dementia.
The trial results were presented at the American Heart Association International Stroke Conference, (Feb 10).
Lacunar strokes, which at affect at least 25,000 people in the UK each year, are thought to be caused by cerebral small vessel disease (cSVD), where small blood vessels deep within the brain become damaged and stop working properly. The researchers investigated cilostazol and isosorbide mononitrate as both thought to improve the function of the inner lining of blood vessels (the endothelium). Problems with the endothelium are thought to play a role in cSVD.
If the results from this study are confirmed in further trials, research leads Professors Joanna Wardlaw (Edinburgh) and Philip Bath (Nottingham), along with the UK Dementia Research Institute, have suggested that the two drugs could become available as a treatment within five years.
The 363 people involved in the trial continued with their standard stroke prevention treatment and took either isosorbide mononitrate or cilostazol individually, both drugs together, or neither.
After one year, participants that took both drugs were nearly 20% less likely to have problems with their thinking and memory compared to the group that did not take either drug. They were also more independent and reported a better quality of life.
Those who took isosorbide mononitrate were less likely to have had further strokes at one year than those who did not take the drug.
Individually isosorbide mononitrate also improved thinking and memory skills, and quality of life, while cilostazol improved independence and mood. But these effects were strengthened when the two drugs were taken together.
The team is now planning to test these drugs in a larger four-year clinical trial, which they hope to start by the end of 2023. They are also looking to test whether the drugs are effective in different conditions linked to cSVD, such as vascular cognitive impairment and dementia.
Professor Philip Bath said: “These are vitally important results and need to be confirmed in larger trials, not just after lacunar stroke but also in other forms of stroke and small vessel disease. The results also support the belief that small vessel disease is due to problems with the lining of blood vessels and treating that may help reverse that abnormality.”
Professor Joanna Wardlaw, Chair of Applied Neuroimaging at the University of Edinburgh and Foundation Chair at the UK Dementia Research Institute, said: “Up until now, lacunar strokes have been treated just like other types of stroke, but lacunar stroke is clearly different. Now we understand more about what is triggering these strokes to attack the brain, we’ve been able to focus our efforts on treatments that can put a halt to this damage.”
“We need to confirm these results in larger trials before either drug can be recommended as a treatment. However, as these drugs are already widely available for other circulatory disorders, and inexpensive, it shouldn’t take too long to move our findings from research into everyday clinical practice.”
More information online:
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Vitamin B5 Offers Promise for New MDS Therapies
People with Myelodysplastic syndromes (MDS), a rare type of blood cancer affecting production of healthy red blood cells, could go on to develop acute myeloid leukaemia (AML). While no curative treatments are currently available for this condition, some medications do help to slow the disease progression – however around 50% of patients become resistant to existing drugs for MDS within 18 months to two years of treatment. Patients are also heavily reliant on red blood cell transfusions which can be painful and dangerous due to iron overload in the blood highlighting the need for newer therapies.
Scientists from Barts Cancer Institute at Queen Mary University of London and the Francis Crick Institute, analysed blood samples from 42 people with MDS and found that the enzyme COASY is critical in regulating red blood cell production in the bone marrow, with partial loss of the enzyme leading to anaemia.
They then tested whether they could boost red blood cell production by supplementing treatments and found that inclusion of vitamin B5 or another metabolite, succinyl- CoA, increased the maturation of red blood cells.
Kevin Rouault-Pierre, Group Leader at Barts Cancer Institute and supervisor of the study, said: “Current treatments for MDS are often associated with reduced quality of life as well as the increased risk of progression to leukaemia. Understanding the biology behind this stem cell disorder is key to unlocking new treatments of the future.
“Our next steps will be to further investigate how to boost red blood cell production and work towards testing new treatments in clinical trials.”
Published in Science Translational Medicine. More information online:
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