Monash discovery central to record-breaking licensing deal

Professor Stephen Jane, Head of Central
Clinical School, Monash University

A suite of drugs developed by the Cancer Therapeutics Cooperative Research Centre (CTx) from early Monash research has just been licensed to global healthcare leader MSD, known as Merck in the US and Canada, in what is believed to be one of the largest preclinical licensing deals involving an Australian discovery.

The drugs – which are inhibitors of protein arginine methyltransferase 5 (PRMT5) – have potential clinical applications in both cancer and non-cancer blood disorders.

The importance of PRMT5 was first discovered by Professor Stephen Jane, Head of the Monash Central Clinical School, who initiated the search for inhibitory drugs.

Unlocking the brain with new stimulation technologies

Associate Professor Kate Hoy

Brain connectivity and neuroplasticity are increasingly investigated and becoming better understood, and the insights are being employed with new technologies for treatment of cognitive disorders and brain injuries.

In this article, Elouise Brennan interviews A/Prof Kate Hoy of the Monash Alfred Psychiatry research centre on how the techniques of transcranial direct current stimulation and transcranial magnetic stimulation are being used for schizophrenia, Alzheimer's and depression. Link to full story.

Predicting patients who require large blood transfusions

By Dr Jodie Abramovitch

Loss of large volumes of blood is responsible for a third of all deaths associated with trauma. The only way to treat a loss of blood, also known as haemorrhagic shock, is via transfusion of blood products. Some trauma patients require transfusion with incredibly large amounts of blood – a massive transfusion (MT) - and their survival may depend on the timely delivery of blood or blood products.  

Director of the National Trauma Research Institute
and senior author Professor Mark Fitzgerald

To create a robust system that allows for the prediction of patients who may require MT, researchers from Monash University and the Alfred Hospital (Trauma Centre, National Trauma Research Institute, Department of Epidemiology and Preventive Medicine and Ambulance Victoria) explored whether use of a ‘shock index’ (SI) calculated before and after arrival at hospital could predict MT. SI is calculated simply by measuring heart rate and dividing it by measured systolic blood pressure.

Of the 6990 major trauma patients who presented at the Alfred Hospital between 2006 - 2012, 5.2% (360 patients) received MT. By using a number of statistical models it was shown that a SI calculated before arrival at hospital was able to significantly improve prediction of MT. Combining the SIs calculated before and after arrival at hospital was only slightly better at predicting MT than the SI measured after arrival at hospital alone.

Considering these observations it was concluded that the SI is a simple option to assist with the prediction of MT. However further study is warranted to validate the SI prospectively. The development and implementation of computer-assisted data collection and prognostication may further enhance the utility of the SI in predicting MT.


Reference: Olaussen A, Peterson EL, Mitra B, O'Reilly G, Jennings PA, Fitzgerald M. Massive transfusion prediction with inclusion of the pre-hospital Shock Index. Injury  2015 May: 46;822-6. 
doi: 10.1016/j.injury.2014.12.009

Reducing cardiac fibrosis

By Dr Jodie Abramovitch

Cardiac fibrosis (scarring) causes the heart to become stiff which affects the ability of the heart to function normally. Cardiac fibrosis can lead to heart failure and is associated with a range of health problems including hypertension, diabetes and obesity.

Dr Anthony Dear

A new class of therapeutics used to treat diabetes, known as glucagon-like peptide-1 receptor (GLP-1R) agonists, help regulate glucose levels in the body. There is evidence that some GLP-1R agonists are able to improve vascular disease in mouse models.

Monash researchers from the Eastern Health Clinical School and the Department of Pharmacology, overseen by Dr Anthony Dear (also associated with the Australian Centre for Blood Diseases) have investigated the effect of a GLP-1R agonist on cardiac fibrosis in a number of different pathological settings.  The recently published work showed that mice with hypertension, obesity, or age induced cardiac fibrosis had reduced evidence of cardiac fibrosis following treatment with a GLP-1R agonist, regardless of diabetic status. Furthermore, reduced levels of inflammatory markers were found within the hearts of treated animals. This reduction in inflammation may be the mechanism behind the observed reduction in cardiac fibrosis.

These results show that GLP-1R agonists may have success in treating cardiac fibrosis, regardless of pathological cause (i.e. hypertension, obesity or age), in humans.

Reference: Gaspari T, Brdar M, Lee HW, Spizzo I, Hu Y, Widdop RE, Simpson RW, Dear AE. Molecular and cellular mechanisms of glucagon-like peptide-1 receptor agonist-mediated attenuation of cardiac fibrosis. Diab Vasc Dis Res. 2016 Jan: 13;56-68.
doi: 10.1177/1479164115605000.

Anaphylaxis to oats – link between food-based moisturisers and food allergy

By Dr Jodie Abramovitch

Food allergy is a growing health issue and, for those affected, can be associated with serious medical outcomes. Allergic reactions to food can range from relatively mild (swelling, rashes) to potentially life threatening (anaphylaxis). 

Allergy Research Group:
(back) L-R Jade Jaffar, Nirupama Varese
Jennifer Rolland (Head), Robyn O'Hehir (Head), Jodie Abramovitch
(front) L-R Sara Prickett, Tracy Phan

Researchers within the Department of Allergy, Immunology and Respiratory Medicine (AIRMed) and the Department of Immunology and Pathology have recently published an interesting case study on oat allergy. A female patient presented with anaphylaxis following consumption of oats in an apple crumble crust. Analysis of the patient’s clinical history noted that, whilst previously able to eat oats without incident, she had been using an oat-based moisturiser to soothe her eczema (broken skin). The patient had also experienced some allergic symptoms (difficulty in breathing) in response to the moisturiser as well as an oat-based bath product.

Experiments were able to show that the patient had oat-specific IgE antibodies (a diagnostic marker of allergy) within her blood. In the presence of oat extract or the oat-containing products, these antibodies were able to activate the patient's basophils, an important cell type activated during an allergic reaction, indicating that they were indeed leading to clinical symptoms when the patient was exposed to oat.

Combined with the clinical history, these data suggest that the patient was sensitised to oat via the application of oat-based products to broken skin. As quoted in a previous article published within this blog, the head of AIRMed and senior author of this case study Professor O’Hehir states that: “This new study adds extra evidence to the argument for skin care preparations to be bland and to avoid agents capable of sensitisation, especially foods.”

Reference: Radhakrishna N, Prickett S, Phan T, Rolland JM, Puy R, O'Hehir RE. Anaphylaxis to oats after cutaneous sensitization by oatmeal in skin products used for the treatment of atopic dermatitis. J Allergy Clin Immunol Pract. 2016 Jan-Feb: 4;152-3

doi: 10.1016/j.jaip.2015.07.005

Development of intestinal gas capsules

By Dr Jodie Abramovitch

Many types of gases are produced within our digestive systems. Alterations in the type and amount of these gases can alter gut function, and potentially be a sign of disease.

Professor Peter Gibson - Head of the
Department of Gastroenterology

In a cross-disciplinary collaborative project including Monash researchers from the Department of Gastroenterology, a new intestinal gas capsule has been developed. These capsules has been designed to be swallowed so as to allow access to the gut in a non-invasive manner. Here they can sample the gases present and transmit their concentration and location (based on time lapsed following ingestion of the capsule) within the gut.

To test the capsules, pigs on high or low fibre diets were given the capsules. Pigs on a high fibre diet had higher concentrations of carbon dioxide (CO₂) and lower hydrogen gas (H₂) within their gastrointestinal tract than pigs given a low fibre diet. These findings were consistent with previous studies which measured gases in the guts of pigs on low and high fibre diets using classical (more invasive) techniques. As such, this study has shown that intestinal gas capsules can effectively provide information on the "where and what" regarding gas production in the gut, information that can only be determined presently by invasive techniques that are not possible to perform on humans.

Though the capsules require further refinement before they can be considered for use in humans, this study has shown that they have great potential to effectively and non-invasively detect gases within the gut. This will allow for a better understanding of the physiology of the gut  and permit easier detection and assessment of gut disorders within the clinic and inform treatment options.

Reference: Kalantar-Zadeh K, Yao CK, Berean KJ, Ha N, Ou JZ, Ward SA, Pillai N, Hill J, Cottrell JJ, Dunshea FR, McSweeney C, Muir JG, Gibson PR. Intestinal gas capsules: a proof-of-concept demonstration. Gastroenterology. 2016 Jan: 150;37-9
doi: 10.1053/j.gastro.2015.07.072

Applications Open: Graduate Certificate in Translational Research

Translational research short course group

Monash is inviting applications for Graduate Certificate in Translational Research. This is a 24 credit point course which can be completed within 0.5 year FT or 1 year PT. 

There are four units - Bioethics Theory and Practice, Introductory Biostatistics, Introduction to Clinical Trials and Translational Research.