Deregulation Of DNA Hydroxymethylases Tet1/ Tet2 Compromises Skeletal Integrity During Ageing And Bone Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,229.00
Summary
Epigenetic modifications of DNA and associated proteins regulate gene expression. A greater understanding of the molecular pathways and associated epigenetic changes that regulate bone cell commitment under normal and pathological conditions will help enhance our ability to diagnose and treat disorders/ diseases that effect skeletal tissues through the pharmacological manipulation of epigenetic modifiers and their gene targets.
Disruption And Restoration Of Motor Control In Musculoskeletal Pathology: Implications For Physiotherapy Management
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
The way in which the nervous system controls muscles and movement may play a role in the development and progression of common musculoskeletal conditions. One of these conditions is patellofemoral pain syndrome which is associated with pain around the knee cap. This condition may result from an imbalance in the activity of the thigh muscles that control movement of the knee cap as the knee bends and straightens. This imbalance is due in part to problems with the control of the muscles by the ner ....The way in which the nervous system controls muscles and movement may play a role in the development and progression of common musculoskeletal conditions. One of these conditions is patellofemoral pain syndrome which is associated with pain around the knee cap. This condition may result from an imbalance in the activity of the thigh muscles that control movement of the knee cap as the knee bends and straightens. This imbalance is due in part to problems with the control of the muscles by the nervous system. Our previous studies have shown that physiotherapy treatment aimed at restoration of the control of the knee muscles results in clinical improvement of the condition. The first part of this project will investigate possible reasons for this muscle imbalance including the effects of pain, swelling and muscle fatigue. Understanding the reasons for the imbalance in muscle activity will help direct and refine more appropriate treatment strategies for this and other musculoskeletal conditions. The second part will assess whether a specific physiotherapy muscle training program for the thigh muscles is more effective in correcting the muscle imbalance than a more generalised thigh strengthening exercise program. The results will help us to better understand why the condition occurs and how we can best assess and treat the problem.Read moreRead less
Common Pathways Influencing Osteoporosis And Atherosclerosis Clinical Risk
Funder
National Health and Medical Research Council
Funding Amount
$443,090.00
Summary
It is recognised there are strong inherited effects on bone density and bone turnover as well as cardiovascular markers like serum cholesterol and arterial function. The study will examine the relationship between osteoporosis and atherosclerosis risk using the powerful twin model and two established large twin cohorts in Sydney and Melbourne. The work may lead to better prediction of common risk factors for these two important conditions.
Defining Treatment Targets To Optimise The Management Of Early Midfoot Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Midfoot osteoarthritis (OA) is a common cause of foot pain and responsible for significant pain and disability. This project will investigate the early structural and functional changes in the midfoot joints and determine the relationships between foot joint loading, structural changes, symptoms and functional impairment. This will identify modifiable factors involved in midfoot OA and define treatment targets to inform the development of effective interventions.
Prevention Of Musculoskeletal Disorders And Cardiovascular Disease – Improving The Evidence-base For Primary Health Care
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Bone and joint problems and cardiovascular disease (CVD) are common in general practice. My research will provide high quality information on how to prevent these conditions in general practice. For example, the studies test: how assessments of people’s risk of a disease might be used to improve their lifestyle behaviours; a new way for GPs to identify patients at high risk of CVD and ways to prevent osteoarthritis progression and to improve bone health in young women and children.
Reducing Knee Load And Slowing Disease Progression With Conservative Interventions In Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$271,503.00
Summary
Knee arthritis is a painful, disabling, costly condition particularly affecting the elderly. As there is presently no cure for arthritis, interventions that slow progression of the disease will reduce the personal and societal burden of arthritis. Recently it has been postulated that specific exercise that targets how the muscles are controlled by the nervous system may have greater disease-modifying effects than exercise aimed at strengthening the muscles. Data are beginning to highlight the co ....Knee arthritis is a painful, disabling, costly condition particularly affecting the elderly. As there is presently no cure for arthritis, interventions that slow progression of the disease will reduce the personal and societal burden of arthritis. Recently it has been postulated that specific exercise that targets how the muscles are controlled by the nervous system may have greater disease-modifying effects than exercise aimed at strengthening the muscles. Data are beginning to highlight the complexity of muscle strategies adopted by the nervous system to compensate for joint derangement in knee arthritis. It is our contention that there may be specific strategies that provide more optimal knee joint loading in relation to slowing disease progression. The first part of this project is to investigate knee control in people with knee arthritis and to evaluate whether this influences disease progression. This will provide the basis for refinement and optimisation of rehabilitation interventions for this patient group. The second part of this project will investigate whether strengthening the hip muscles in patients with knee arthritis influences knee load and hence disease progression. Hip muscle strengthening is currently not routinely included as part of the management of knee arthritis. If the results of this project find it to be effective, then hip muscle strengthening can be recommended for treating knee arthritis.Read moreRead less
Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms c ....Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms common to more than one MPS type include mental deterioration, blindness, abdominal organ enlargement and bone growth problems leading to short stature and bone loss. My laboratory has had a long-term interest in developing treatment for MPS and our research led to the clinical implementation of enzyme replacement therapy (ERT) for MPS VI in 2005. While providing the first effective, multi-tissue treatment for MPS, our research showed that several tissues were not responsive to ERT. These are the brain, cartilage and cornea, thus children on ERT regimens will still suffer from mental retardation, arthritis and blindness. With the goal of treating these particular tissues we have developed a new approach to MPS therapy called substrate deprivation therapy (SDT). Instead of adding back the missing enzyme, SDT acts by decreasing gag production which in turn reduces the level of accumulated gag in cells. SDT results in the correction of MPS cells in culture and reduces several key clinical symptoms in the mouse model of MPS IIIA. In this proposal we will extend our research to evaluate the effect of SDT on brain and bone-joint pathology. Evaluation of efficacy will take place in the MPS VII mouse which exhibits both brain and bone disease and in a new model of MPS IVA developed specifically for this study which exhibits a joint pathology unique amongst the MPS disorders.Read moreRead less
The Role Of Endogenous Glucocorticoids In Autoimmune Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$693,185.00
Summary
Inflammatory joint diseases affect millions of people worldwide and in most patients these often chronic conditions can not be cured. In an experimental model of arthritis we have found that bone cells can modify the severity of inflammation when certain hormonal signals are blocked. This study will identify the mechanisms underlying these hormonal effects with the aim to find new targets for efficient treatments for arthritis.
Is Physiotherapy Beneficial For People With Hip Osteoarthritis?
Funder
National Health and Medical Research Council
Funding Amount
$629,508.00
Summary
Hip osteoarthritis (OA) is a chronic joint disease that causes pain and reduced function. There is currently no cure so safe, effective treatments are needed. Physiotherapy plays a role in the management of hip OA but there is little evidence of its effectiveness. This project will determine the effects of a 12 week physiotherapy program on pain and function in 148 people with hip OA. The results will help with recommendations as to the best ways to treat this chronic condition.
Skeletal disease is a major problem for children with mucopolysaccharidoses (MPS). Patients suffer from early onset osteoporosis and osteoarthritis, severely affecting their quality of life. We will evaluate a lentiviral gene therapy vector developed in-house for its capacity to transduce bone, cartilage, synovial and ligament cells in a mouse model of MPS VI. Our goal is to generate high level, sustained expression of the deficient MPS enzyme and alter the course of skeletal disease in MPS.