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Centenary Institute - Medical Research
Centenary Institute - Medical Research

New treatment discovery for vascular disorder

Researchers from the Centenary Institute have discovered a potential new therapy for cerebral cavernous malformations (CCMs), a devastating disease that often affects young people and can result in stroke and seizures.

Using mouse models, the researchers found that use of the drug, CD5-2 helped normalise the vascular disorders, and inhibited the development and reduced the size of existing lesions.

The study was published in the highly respected international science journal PLOS Biology.

“CCMs are vascular lesions comprising clusters of abnormally thin and leaky blood vessels. Stroke or seizures can occur when blood from these vessels leaks into the surrounding brain tissue. We can’t predict when this will happen or how frequently,” said senior author on the research paper Professor Jennifer Gamble, Head of the Vascular Biology Program at the Centenary Institute.

“Most often, people don’t realise they have the disease until they have an event such as a seizure. Currently, there is little in the way of effective medical treatment for CCMs except for surgical removal of the most dangerous lesions which is limited by the size and depth of the lesions,” she said.

In the study, Professor Gamble and collaborators were able to show that a protein called VE-cadherin, critical to maintaining a healthy blood vessel lining, was seen at lower levels in mice with CCM lesions.

“We then used the drug CD5-2 to elevate VE-cadherin levels, resulting in a reduction in the lesions that were present in our CCM mice,” said Professor Gamble.

The drug CD5-2, developed by the Centenary Institute and collaborators was initially designed to combat the development of solid cancers by reducing and repairing damage caused by inflammation in blood vessels. It has since been found to have other potential benefits including as a treatment to prevent sight-loss in people with diabetes.

“Our research journey with CD5-2 is exciting,” says Professor Gamble. “CD5-2 is a drug that improves leaky blood vessels and this is a feature of many chronic diseases. We have now shown that CD5-2 is a potential novel therapy for CCMs, a disease with surgery as the only option, and that not always possible, especially if patients have multiple lesions. This discovery could lead to the first effective, non-invasive treatment option for CCMs which would be truly heartening for sufferers.”

Professor Gamble believes that CD5-2 may yield even further health benefits with research into the drug and other disease areas still ongoing.

Read the full media release here.

Access the publication here.

$3m to strengthen Centenary Institute research

World-class study into inherited heart disease as well as Alzheimer’s disease have been boosted after two Centenary Institute researchers successfully secured a total of $3m in highly competitive National Health and Medical Research Council (NHMRC) funding.

Associate Professor Jodie Ingles, Head of the Institute’s Clinical Cardiac Genetics Group in the Molecular Cardiology Program (pictured left), was awarded a Clinical Trials and Cohort Studies Grant in excess of $2m. This will fund a five-year study into inherited cardiomyopathies involving approximately 2,500 participants. The cohort of participants will be comprehensively investigated and followed over time, making this an extremely unique and important resource for better understanding these diseases.

“Inherited cardiomyopathies such as hypertrophic cardiomyopathy affect the heart muscle and are passed on genetically in families. There can be important health implications, including a risk of heart failure and sudden cardiac death,” says A/Prof Ingles.

“There are many aspects of how we manage and treat inherited cardiomyopathies that are not well understood. Our study will follow participants over time to gain critical clinical and genetic insights. In doing so, we can then provide tailored advice regarding management, treatments, prognosis and family screening regarding the disease,” she says.

Professor Jenny Gamble, Head of the Vascular Biology Program at the Centenary Institute was awarded an Ideas Grant of just under $1m. The grant will fund research into Alzheimer’s disease, the most common form of dementia. Supported by secondary Chief Investigator Doctor Ka Ka Ting also from the Centenary Institute, the research program will focus on the blood vessels of the brain and their potential role in Alzheimer’s development and progression.

“Alzheimer’s disease is an age-related neurodegenerative disease that is on the rise due to our ageing population. Although we don’t know yet what causes the disease it is thought that changes to the blood vessels in the brain are the earliest sign of Alzheimer’s and actually predispose the patient to the development of the disease,” says Professor Gamble.

“This grant will support our work on investigating the cells that form the barrier between the blood and the tissues, endothelial cells. We have identified significant age-related changes in these cells.  We want to determine if the breakdown and dysfunction of these cells with age actually leads to, or makes Alzheimer’s Disease more likely. If this is the case, our work will open the door to an entirely new approach to combatting the disease,” she says.

In addition to the two Grants, the Centenary Institute’s Laura Yeates received a NHMRC Postgraduate Scholarship for her study into ‘Caring for families affected by sudden cardiac death of a young relative due to genetic heart disease.’ Centenary’s Natalia Pinello also received a NHMRC Postgraduate Scholarship for her study into ‘RNA 5-hydroxymethylation in Haemopoiesis and Leukaemia.’

Read the full media release here.

Centenary researchers receive cardiovascular disease grants totalling $2.25m

Three Centenary Institute researchers based in Sydney have been awarded grants totalling $2.25m that will help support the diagnosis, treatment and prevention of cardiovascular disease.

The highly competitive grants, from the first round of the NSW Cardiovascular Disease Research Capacity Building Program, were awarded to Centenary Institute’s Professor Christopher Semsarian (left), Professor Jennifer Gamble and Dr Richard Bagnall (right).

Professor Christopher Semsarian, awarded a ‘Cardiovascular Disease Clinician Scientist Grant’ was happy to receive the funding, noting that the grant would support his research into identifying new genetic causes of inherited heart diseases, including that of sudden cardiac death (SCD) in the young.

“We want to find the underlying molecular mechanisms responsible for these life-threatening heart diseases, to provide answers to families as to why their child died suddenly and how can we help prevent these inherited heart diseases from claiming other family members as well as individuals from across the wider community,” he said.

Professor Jennifer Gamble, who was awarded a ‘Cardiovascular Disease Senior Scientist Grant’ will use her funding to explore molecular changes in endothelial cells as they undergo cellular ageing.

“Endothelial cells line blood vessels and changes in their function and structure can result in leaky blood vessels and a chronic inflammatory state,” said Prof Gamble. “These changes contribute to the initiation and progression of age-associated disease including cardiovascular disease. We need to find out what’s happening with these cells at a deeper level as an essential first step to developing potential new therapeutics.”

Dr Richard Bagnall who also received a ‘Cardiovascular Disease Senior Scientist Grant’, will use the funding to support his molecular biology and bioinformatics work into developing improved genetic testing for inherited heart diseases.

“High volumes of DNA sequencing data can now be generated, but it requires sophisticated software and computers to make sense of all that information,” said Dr Bagnall. “I’ll be undertaking a computational analysis of gene sequencing, followed up by laboratory analysis, so that we can precisely identify specific cardiovascular diseases, aiding future diagnostic and treatment approaches.”

Read the full media release here.