Menzies Institute for Medical Research
Research Highlights 2015
The University of Tasmania’s Menzies Institute for Medical Research exists to perform internationally significant medical research leading to healthier, longer and better lives for Tasmanians. We have been making discoveries to improve the health of our community since our establishment in 1988. Our research covers five themes, each one addressing a different group of diseases prevalent in the Tasmanian community. Once again in 2015 we have delivered remarkable results that will contribute to improving the health and wellbeing of our community and save many lives. Our research highlights for 2015 are listed here. Research by Dr Seana Gall and PhD student Jing Tian, left, has quantified the average weight gain in smokers who quit.
Public Health and Primary Care Can the risk of developing Multiple Sclerosis (MS) be changed? The important risk factors for developing MS are thought to interact to have a cumulative effect on MS risk. New Menzies research has investigated five of the main risk factors for MS. In order of strength of association, these are an immunological gene, smoking, sun exposure, history of glandular fever and levels of vitamin D. For each additional risk factor, the risk of MS doubled. People who had four or five risk factors were over 20 times more likely to develop MS than those who had no risk factors. Together, the five risk factors account for almost 64% of the risk of developing MS. Indeed, over half of the risk of developing MS can be modified through lifestyle or environmental changes. This is important since it indicates that preventative efforts directed against these risk factors are likely to have a substantial effect on MS in the population. Weight gain after quitting smoking. Fear of weight gain is a commonly cited reason for not quitting smoking, despite evidence that quitting will result in better overall health. Researchers have quantified the weight gain for smokers who quit, and the difference in weight gain between quitters and continuing smokers. By combining data from 63,403 quitters and 388,432 continuing smokers, they found that people who quit smoking gained an average of 4.1kg in weight over about five years, 2.6 kg greater than the gain in continuing smokers. This weight gain was greater in women than men, and greater in studies conducted in
North America than Asia. The reasons for the weight gain after smoking are complex but probably relate to changes in brain activity and metabolism after quitting. Compared with the harm associated with smoking, the extra weight gain commonly seen after smoking cessation is relatively modest and should not discourage smokers from quitting. Funding of general practice after-hours care. This research looked at whether there was objective data to support widespread concerns about the way government has supported after-hours general practice care. We identified specific problems with the way funding was being allocated to this care. The study’s findings fed directly into a Tasmanian funding model and are expected to stimulate similar research across the country to help refine policy developments.
Musculoskeletal Health and Diseases Does fish oil help osteoarthritis? Fish oil is commonly used to treat osteoarthritis, but until now there has never been a clinical trial into the efficacy of this. The aim of this trial was to determine whether high-dose fish oil was superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis. We enrolled 202 patients with knee osteoarthritis and regular knee pain and randomised them to 15 mL/day of high-dose fish oil or 15 mL/day of low-dose fish oil. Pain was measured at three, six, 12 and 24 months, and change in cartilage
volume at 24 months. We saw improvement in both groups, but greater improvement in pain and function in the low-dose fish oil group. There was no difference between the two groups in cartilage volume loss at two years. The low dose fish oil/canola oil combination appeared to have better efficacy in reducing pain at two years, suggesting that this requires further investigation. Genetic factors and pain. The aim of this study was to investigate whether offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis have an increased risk of worsening knee pain over eight years, as compared to people with no family history of knee osteoarthritis. We studied 115 offspring and 104 controls (average age 48 years). Knee pain was assessed at two years and 10 years. Magnetic resonance imaging of the right knee was performed to assess knee cartilage defects, bone marrow lesions, meniscal extrusion and tears. Compared with controls, the prevalence of knee pain for offspring was similar after two years (56% versus 54%) and higher after 10 years (74% versus 54%). Over eight years, offspring more frequently had an increase in total knee pain (66% versus 41%) in all subscales apart from walking. Thus, offspring with a family history of knee OA have an increased risk of worsening knee pain, which is independent of structural factors. Inflammation and osteoarthritis. Osteoarthritis is usually considered to be a non-inflammatory condition due to wear and tear and thus an inevitable part of ageing. This study described the associations between fluid on the knee and structural changes in 977 older adults over three years. We concluded that there are independent associations between fluid on the knee and knee cartilage defects in both cross-sectional and longitudinal analyses of the knee. This opens the door for therapy with newer antiinflammatory agents.
Cardio-Metabolic Health and Diseases Home blood pressure measurement: guidelines for doctors and patients. Blood pressure measured by a doctor in the clinic is a screening tool with some important limitations on accuracy that result in higher readings than the true underlying blood pressure. One way to overcome these problems is for people to measure their own blood pressure using a standardised approach at home, but to date there has been little guidance as to how to do this. Menzies investigators led a national expert panel to produce guidelines on home blood pressure monitoring, as well as a series of web accessible practical documents for patients and doctors to improve the measurement and education around home blood pressure monitoring. Education sessions continue to be conducted around Australia. Vitamin D supplementation: is it worthwhile for cardiovascular protection? To date, observational data has implicated low vitamin D in adverse cardiovascular health, such as increased blood pressure and increased stiffness of the large central arteries. But there has been no randomised controlled trial evidence to support using vitamin D to reduce cardiovascular problems. This study tested this hypothesis over 12 months among 241 people who were randomised to a monthly dose of vitamin D compared to placebo. We found absolutely no effect of vitamin D on the cardiovascular system and concluded that supplementation for this purpose is not worthwhile. Early stages of heart failure. A major interest of Menzies’ cardiovascular researchers is the detection of the early stage of the disease that may precede the development of heart failure symptoms. This year, our group published an important study of 510 asymptomatic patients with type 2 diabetes mellitus, hypertension or obesity, where we showed that heart muscle thickening, elevated cardiac pressure and abnormal myocardial deformation were independently associated with impaired exercise capacity. This important observation about the methods for recognition of early heart disease is helping to inform our efforts to identify cardiac problems in the Tasmanian community. Other advances from the cardio-metabolic group in 2015 have included the growth of the Menzies’ clinic for difficult-tomanage blood pressure and the one-year follow-up of patients in our Statewide randomised trial to identify the benefit of early diagnosis of heart failure (Tas-ELF). We have seen progress in studies aimed at reducing hospital re-admission for heart failure and targeted lowering of central blood pressure. Our $2.6 million grant to identify the value of coronary CT in family members of patients with premature coronary disease has started strongly, with screening of over 100 patients.
Pan Feng and Xia Weng, who are both PhD students in the Musculoskeletal Health and Diseases research theme, both received a Menzies Ten of the Best award for research achievement.
Cancer, Genetics and Immunology Major contribution to understanding glaucoma. Menzies researchers and collaborators have provided a major contribution to our understanding of the common genetic variation underlying primary open angle glaucoma (POAG) susceptibility. The research identified three new sites on the genome implicated in risk for POAG. It highlighted related candidate genes and pathways that might be involved in developing glaucoma. These new locations, in addition to the previously known-risk locations, will improve risk assessment for glaucoma, with better opportunities for the management of high-risk individuals.
Saving the Tasmanian devil. Researchers from Menzies and the University of Tasmania’s School of Medicine have made significant steps on the path towards a vaccine against Devil Facial Tumour Disease (DFTD), the transmissible cancer that has wiped out around 80 per cent of the Tasmanian devil population. Based on laboratory data, researchers have induced an immune response in Tasmanian devils against the DFTD tumour cells. Nineteen immunised devils have since been released into Narawntapu National Park in the first test of the vaccine in the wild.
New breast cancer research. Our initial focus has been on some of the health problems that result from breast cancer treatment and the challenges of treating secondary breast cancer or metastatic disease. In the first group, our clinical studies are aimed at decreasing the risk of women developing short or long term arm and shoulder disability and complications such as lymphedema after breast surgery. Our laboratory-based research into secondary breast cancer revolves around the investigation of a group of proteins called integrins. Changes in these proteins occurs in a number of types of cancer cells, enabling them to move from the primary tumour, in this case breast tumour, through the body to set up new tumours. Through our previous research we have discovered the ways in which these proteins change during the spread of prostate tumour cells and our new research program will now examine these changes in breast cancer.
Below: The Menzies Blood Pressure Group, led by Associate Professor James Sharman, seated on far left, is helping to improve the care of people in the community with problems related to high blood pressure.
Above: Dr Alex Kreiss, Dr Ruth Pye and the leader of the Tasmanian devil research team at Menzies, Professor Greg Woods, are all working towards the development of a vaccine for DFTD.
Neurodegenerative Diseases/Brain Injury Causes of Motor Neuron Disease (MND). Work published in 2015 as a feature article in the journal Disease Models and Mechanisms has brought us a step closer to understanding the cause of MND and where it begins in the central nervous system. Using newly developed experimental models we have found that MND is likely triggered in the spinal cord due to “excitoxicity” or over-activation of motor neurons. It then propagates or spreads forward to the muscle, ultimately leading to degeneration of the connection. Understanding the excitotoxic mechanisms of motor neuron loss and the degeneration at the point where nerves and muscles meet is a vital step in the pathway to developing therapeutics for MND. New data on Traumatic Brain Injury (TBI): TBI continues to be a leading cause of death and disability in developed nations, with the estimated cost of new cases reaching several billions of dollars in Australia alone. Critically, the incidence of TBI is highest in people during the most productive years of their lives and frequently results in prolonged or lifelong motor and/or cognitive impairments. There are currently no drugs available to prevent,
minimise or reverse the primary damage and complex secondary changes that develop following TBI. Menzies researchers have new data that suggests that post-injury treatment with compounds that stabilise the structural integrity of the cell could positively affect many aspects of the brain’s response to trauma. Using a primary culture or ‘brain in a dish’ approach, it was found that treatment with the drug Epothilone D was safe, with no evidence of toxicity. Most importantly it was found that treatment of neurons with EpoD after injury resulted in a significant increase in nerve growth that was highly dose dependent. These investigations represent the first critical step towards development and testing of highly targeted treatments for people with TBI.
Associate Professor Tracey Dickson leads the Neurodegenerative Diseases/Brain Injury research theme at Menzies. Her research group is working hard to build a greater understanding of Motor Neuron Disease and treatment for Traumatic Brain Injury.
Would you like to know more?
If you would like information on how you can donate to medical research at Menzies, please contact the Institute Advancement Manager on +61 (0)3 6226 4236. Cover image: Associate Professor Kathryn Burdon and colleagues have made a major contribution to our understanding of the common genetic variation underlying primary open angle glaucoma. She is also working on understanding the genetic causes of keratoconus, which affects the clear window at the front of the eye. Photo by Peter Mathew/Flinders Opthalmology ABN 30 764 374 782
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