Heart Foundation support boosts Monash biomedical research
Three Monash Biomedicine Discovery Institute (BDI) research projects - aimed at safeguarding women and babies from the potentially fatal preeclampsia; reducing brain damage and functional impairment after stroke; and developing a treatment to stabilise and potentially reverse aneurysms arising in the body’s main aorta - have all been awarded coveted Heart Foundation grants.
The grants were part of funding for 53 projects worth $13.1 million awarded by the Heart Foundation recently to investigate the causes, treatment and prevention of heart disease, stroke and related disorders.
Professor Kate Denton, Head of Monash BDI’s Cardiovascular Disease Program, was delighted to congratulate the three successful BDI awardees of Heart Foundation Vanguard Grants.
“This is an excellent outcome for the BDI and is a well-deserved recognition of the work of each of these investigators. Well done! A great end to the year,” Professor Denton said.
Preeclampsia, a complication in pregnancy characterised by uncontrolled high blood pressure, can be immediately life-threatening and can lead to long-term medical conditions for mother and baby.
Dr Bubb was awarded a Vanguard Grant of nearly $150,000 over two years to investigate a hormone – C-type natriuretic peptide (CNP) – that could be a cause of preeclampsia and which may offer a new target for its treatment. Dr Bubb and collaborators recently discovered that CNP plays a critical role in blood vessel growth and development.
Preeclampsia usually begins after 20 weeks of pregnancy, however traditional medicines used to lower blood pressure are generally ineffective in treating it. Delivery of the placenta, and often the premature birth of the baby, is the only way to resolve it, putting the baby at risk of lifelong complications. Alarmingly, mothers who experience preeclampsia have a four-fold increased risk of developing non-pregnancy related hypertension, pre-disposing them to higher morbidity and mortality from cardiac disorders such as heart attack, heart failure and stroke.
Dr Bubb will use the funding to determine the role of the CNP signalling pathway and see if this can be therapeutically managed.
“The really big picture is that one day we can give women a pill with CNP inside that will help reduce blood pressure during pregnancy at least until they reach full-term so babies aren’t delivered early,” Dr Bubb said. “We would also determine if this pathway has any impact on them later in life in terms of cardiac dysfunction and intervene early.”
She will work with Professor Stephen Nicholls, Director of Monash Heart and the Victorian Heart Hospital; the BDI’s Dr Katrina Mirabito Colafella; Professor Adrian Hobbs, Queen Mary University of London and Dr Anthony Ashton, University of Sydney.
Dr Broughton is using his two-year Vanguard Grant of $130,000 to further promising preliminary research investigating whether exosomes released from placenta-derived stem cells can reduce brain damage and functional impairment after stroke. “Exosomes are nano-sized packages of ‘goodies’ that can be optimised to the environment – like a pharmacy on wheels,” Dr Broughton said.
The project builds on previous research by Dr Broughton and collaborators Associate Professor Rebecca Lim from the Hudson Institute of Medical Research, and Professor Chris Sobey from La Trobe University, showing that injected stem cells can provide neuroprotection even when administered three days after a stroke – work that’s now the subject of a Monash-led phase 1 clinical trial.
Exosomes could improve on such stem cell treatment because they can be stored at minus 20 degrees Celsius and prepared within minutes, including in an ambulance, whereas stem cells need to be prepared in a hospital. They are also smaller and safer for injecting intravenously and can be administered in higher amounts, offering greater protection, Dr Broughton said.
Stroke is the world’s second leading cause of death. “Current treatments – pharmacological and surgical – can only be performed in hospital. We urgently need new treatment options,” Dr Broughton said. “Current treatments don’t target cell death,” he said. “Exosomes can target mechanisms to prevent cell death and activate mechanisms for repair and regenerative mechanisms.”
Dr Broughton is collaborating with Associate Professor Lim, and Professor Sobey, on the project.
Abdominal aortic aneurysm (AAA) is an irreversible, asymptomatic condition where the abdominal aorta – the body’s main artery – is weakened and dilated, eventually rupturing, resulting in a death rate of 50-80%. Currently, monitoring the aneurysm’s diameter and surgery is the only treatment option. However, surgery is only conducted when the aorta exceeds 55 millimetres in diameter – most measure less than this and with no drug treatments available the aneurysm is a ‘time-bomb’ for patients.
Dr Gaspari and colleagues recently discovered a new drug that appears to stabilise established AAAs and which may also be a potential biomarker for the condition. Dr Gaspari said exciting preliminary data revealed that animal models treated with drugs that selectively block the activity of the enzyme insulin regulated aminopeptidase (IRAP) protected against the development of AAA.
The finding was made serendipitously during previous research by Dr Gaspari that established the protective effect of inhibiting IRAP in the cardiovascular system and particularly in reducing fibrosis in the heart and kidneys. This earlier work led to the establishment of start-up company, Inosi Therapeutics, of which she is co-founder.
The current project will test the feasibility of drugs that selectively block IRAP activity to prevent the development of, stabilise and potentially reverse established aneurysms in preclinical models.
Dr Gaspari said she was “over the moon” to receive Heart Foundation Vanguard funding to further the research. “This grant was crucial for being able to maintain our ongoing research,” she said. “It’s difficult in these times to keep people in the lab and have the continuity required for successful research outcomes.”
Also working on the project are; the BDI’s Professor Robert Widdop and Associate Professor Siew Yeen Chai and Associate Professor Anthony Dear, head of Monash University’s Eastern Clinical Research Unit translational research division.
Read about all of the Heart Foundation Research Award Recipients 2020 here.
See a full list of the Monash recipients here.
About the Monash Biomedicine Discovery Institute at Monash University
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.