The Next Generation Of Biomaterials; In Vivo Assessment Of Lumbar Spinal Fusion Biodegradable Interbody Cages
Funder
National Health and Medical Research Council
Funding Amount
$85,932.00
Summary
Back pain represents one of the major health and economic problems facing the western world. Surgery is an inevitable outcome for many sufferers and involves the implantation of metallic rods screws, plates or cages. Biodegradable implants have theoretical advantages, but until now no material has existed that can sustain he rigours of implantation into a load bearing site. We have developed such a material which will lead to improvements in the treatment of many orthopaedic conditions.
Delayed Neuronal Death After Peripheral Nerve And Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
After injury to the nervous system, even under optimal conditions for regeneration of broken nerve processes (axons), there is little chance of normal function being restored because few regrowing axons will find appropriate cells to connect with. The time taken for many regrowing axons to reach their targets can be so long that both the axons and their targets lose the ability to recognize each other. Equally importantly, some damaged nerve cells die over the months that follow an injury. This ....After injury to the nervous system, even under optimal conditions for regeneration of broken nerve processes (axons), there is little chance of normal function being restored because few regrowing axons will find appropriate cells to connect with. The time taken for many regrowing axons to reach their targets can be so long that both the axons and their targets lose the ability to recognize each other. Equally importantly, some damaged nerve cells die over the months that follow an injury. This slow loss of nerve cells can lead to progressive and ongoing deterioration. Given recent advances in our understanding of how to improve axon regeneration, the degree of functional recovery could be disappointing unless we know more about how to prevent these neurones from dying. This project will use rats as experimental animals to try to understand which types of nerve cells are likely to die or survive after injury to peripheral nerve trunks or to the spinal cord. We will investigate two regions of the nervous system that are commonly involved in injuries in people. After injuries to limb nerves, people lose sensation and movement and can unpredictably develop chronic conditions such as neuropathic pain (unrelated to the damage and often occurring spontaneously) as well as poor blood flow and wound healing in the hands-feet. After most injuries to the spinal cord, the lower part of the cord beyond the injury (in particular the lumbosacral cord controlling hindlimb movement and sensation and the function of bladder, bowel and sexual organs) is often disconnected from the brain leading to paralysis and disrupted control of pelvic organ function. We will identify and study specific populations of nerve cells with sensory (mainly pain-sensing) functions and four identified groups of nerve cells in the lumbosacral cord that project to the brain. Once we know which nerve cells do not survive, we will search for the likely causes of their death and ways to prevent it.Read moreRead less
Interrelationships Between The Disc And Bone Of Lumbar Spinal Segments
Funder
National Health and Medical Research Council
Funding Amount
$423,625.00
Summary
The cause of back pain due to osteoarthritis, osteoporotic vertebral crush fracture, and ageing is poorly understood. Vertebral deformity, intervertebral disc disorganisation, and change to vertebral bone structure are features associated with degeneration of the spine and with back pain. Degenerative disc disease is one of the major causes of back symptoms and is believed to be associated with degeneration of the spine. Spinal degeneration includes disc degeneration, facet joint osteoarthritis, ....The cause of back pain due to osteoarthritis, osteoporotic vertebral crush fracture, and ageing is poorly understood. Vertebral deformity, intervertebral disc disorganisation, and change to vertebral bone structure are features associated with degeneration of the spine and with back pain. Degenerative disc disease is one of the major causes of back symptoms and is believed to be associated with degeneration of the spine. Spinal degeneration includes disc degeneration, facet joint osteoarthritis, compromised vertebral body bone quality, muscle and ligament alterations. It is assumed that these changes result in increased or abnormal spine motion and modified load distribution across the spinal joint. It has been found that with age, there is increased disorganisation of the intervertebral disc and decreased quality of vertebral cancellous bone. However, bones with the same density within the range of normal subjects, can show selective loss of bone structure and reduced load-bearing capacities of these vertebrae. An important concept here is that even for a given bone mass, fracture risk increases with age, supporting the view that there is a component of bone fragility that is independent of mass. Increased bone fragility may be associated with compromised cancellous bone structure. While the relationship between disc degeneration and changes in vertebral bone is commonly invoked, the mechanisms of this relationship have largely been overlooked, with age changes given more attention. However, it may be that intervertebral disc disorganisation modulates age-related bone changes within the spine. Disc degeneration may influence trabecular bone responses before changes with age put the patient at risk of vertebral crush fracture. We propose that the mature disc cannot effectively regenerate after damage, and thus responses to disc damage will be more readily observed in vertebral bone architecture than in the disc.Read moreRead less
Pharmacological Modulation Of Microglial Responses After Transient Forebrain Ischaemia In Rats
Funder
National Health and Medical Research Council
Funding Amount
$170,906.00
Summary
A stroke is caused by an acute blockade of blood flow to a brain region and is normally caused by a clot in the artery that supplies blood to that region. Within minutes, the region of the brain that is receiving no blood flow, dies and so the functions controlled by that region cease. If this region controls key functions such as breathing then the patient dies and this occurs in about one third of patients. However, in the majority of patients, the blockage affects parts of the brain controlli ....A stroke is caused by an acute blockade of blood flow to a brain region and is normally caused by a clot in the artery that supplies blood to that region. Within minutes, the region of the brain that is receiving no blood flow, dies and so the functions controlled by that region cease. If this region controls key functions such as breathing then the patient dies and this occurs in about one third of patients. However, in the majority of patients, the blockage affects parts of the brain controlling movement of limbs or speech and so these patients suffer permanent disabilities. Not surprisingly, stroke is the most common life-threatening neurological disease and the major cause of disability in adults over 45. Apart from the profound effect stroke has on the patient and the family, the annual cost of disability to the Australian community is approx $ 1 billion. If the disability could be minimised by reducing institutionalization then the cost saving would be great. Research is being carried out to define how nerves die when they have insufficient blood supply and progress has been made in understanding the biochemical basis of this process. Such knowledge opens the way for the design of novel drugs to delay nerve death. Our laboratory has been successful in designing a novel drug, AM-36 that minimises nerve death in the forebrain of rats that have had the blood supply to the forebrain interrupted for 3 to 5 hours. A recent report has shown that a stroke in the forebrain can lead to nerve damage in the spinal cord and this could contribute to impaired walking in stroke patients. This is an unexpected finding and this project seeks to define how and when nerves in the spine die after a stroke in the forebrain. Such information should then lead to the rational design of drugs to minimise the death of nerves in the spinal cord as well as in the forebrain.Read moreRead less
Cellular Mechanisms Underlying Neurodegenerative Disease And The Neuronal Response To Trauma
Funder
National Health and Medical Research Council
Funding Amount
$406,264.00
Summary
Brain and spinal cord injury are major causes of death and disability, with degenerative diseases similarly affecting large proportions of the population. The singular objective of my research proposal is to increase our understanding of the molecular and cellular processes by which nerve cells respond to trauma and diseases such as Alzheimer’s and Parkinson’s, and to identify new therapeutic approaches aimed at encouraging the repair of damaged cells.
Immediate Cooling And Emergency Decompression (ICED) For The Treatment Of Spinal Cord Injury: Pilot, Safety And Feasibility Studies
Funder
National Health and Medical Research Council
Funding Amount
$600,008.00
Summary
Victims of Spinal Cord Injury are young, have severe paralysis, complex needs and high lifetime costs. Although urgent surgery greatly improves outcome, it is difficult to achieve because of logistical difficulties. To expand the time window for early surgery, it is proposed to immediately cool patients. This project will conduct the pilot studies necessary before commencing a clinical trial of immediate cooling and emergency decompression (ICED) in patients with cervical spinal cord injuries.
Therapeutic Development Of A Novel EphA4 Antagonist For Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$687,105.00
Summary
Spinal cord injuries impose a significant burden on patients and their carers. At present, there are no treatments for spinal cord injury that provide functional improvement. This research program will develop a novel therapeutic molecule, EphA4-Fc, which promotes axonal regeneration and delivers significant functional improvement. We will determine the most effective protocol for EphA4-Fc administration and the physiological and functional outcomes of these treatment regimes.
Unravelling The Riddle Of Spondylolysis: A Novel Biomechanical Approach Incorporating Innovative Strain Field Mapping, Acute Fracture Path Mapping And In Vivo Weightbearing Spinal Kinematics Derived From Open Magnetic Resonance Imaging.
Funder
National Health and Medical Research Council
Funding Amount
$334,673.00
Summary
Low back pain represents a significant social and economic burden in Australia and can be debilitating for individuals. This project aims to understand the biomechanical origins and consequences of spondylolysis, a common spinal stress fracture affecting both children and adults. The results of these studies will contribute to improved prevention, detection and treatment of this spinal condition, and reduce the incidence of more serious spinal problems which can occur subsequent to spondylolysis ....Low back pain represents a significant social and economic burden in Australia and can be debilitating for individuals. This project aims to understand the biomechanical origins and consequences of spondylolysis, a common spinal stress fracture affecting both children and adults. The results of these studies will contribute to improved prevention, detection and treatment of this spinal condition, and reduce the incidence of more serious spinal problems which can occur subsequent to spondylolysis.Read moreRead less
INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX METALLOPROTEINASES
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem w ....Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem will increase in severity over the next few decades. American Bureau of Census data indicate that between 1990 to 2010 the number of people >45 years will increase from 82 to 124 million, the number of elderly in emerging countries will also increase between 200 to 400% in the next 30 years. In the United States, back-pain is the second most common reason that people visit a physician and medical conditions related to back-pain account for more hospitalisations than any other musculoskeletal disorder. Despite its high incidence, associated problems of incapacity and economic implications, costed at $100 million per annum in Australia in 1992, and US$100 billion globally in 1999-2000 (Dorland Data Networks, PA, USA) the causes of low back-pain are still poorly understood. Disc disease is responsible for 23-40% of all cases of low back-pain. The management of discogenic low back-pain is currently empirical, directed either toward life-style changes to minimise symptomatology or to surgical resection or spinal arthrodesis to restrict articulation. Based on our recent findings and those of colleagues over the last 16 years, it is our strong conviction that it should be possible with a better understanding of disease mechanisms and with the use of modern technologies to inhibit, reverse or ideally prevent disc degeneration. Without such basic research there will be no scientific foundation upon which prospective therapies may be based.Read moreRead less
Novel Functional Imaging For Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$564,848.00
Summary
Age-related macular degeneration (AMD) is an eye condition which affects the central retina (the macula) resulting in a loss of central vision. The lack of appropriate clinical tests to monitor the progression of AMD at the early stages of disease hampers the discovery of novel interventions aimed at preventing the development of advanced vision-threatening AMD. In this project, we will investigate the use of a quick and non-invasive imaging technique for monitoring AMD progression.