Peptides Bound To Commonly Used Orthopaedic And Dental Biomaterials:In Vitro And In Vivo Effect On Osteogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$273,428.00
Summary
In 1992, the orthopaedics industry fitted some 300,000 prosthetic devices, artificial hips, knees, giving this industry a global market of $2.1 billion with a projected market growth exceeding 10% per annum. In (1994-5) 5,717 prosthetic hips and 4,593 knees were surgically implanted in NSW of which 14% of hips and 9.5% of knees were revisions. Considerable health funding is allocated to joint replacement for the nation, although successful, outcomes are finite. Importantly, and aside from costs, ....In 1992, the orthopaedics industry fitted some 300,000 prosthetic devices, artificial hips, knees, giving this industry a global market of $2.1 billion with a projected market growth exceeding 10% per annum. In (1994-5) 5,717 prosthetic hips and 4,593 knees were surgically implanted in NSW of which 14% of hips and 9.5% of knees were revisions. Considerable health funding is allocated to joint replacement for the nation, although successful, outcomes are finite. Importantly, and aside from costs, patients morbidity is high. The major cause of long-term failure of these prosthetic replacements is aseptic loosening, the result of bone loss at the bone-device interface. Novel approaches to development of more efficient implant materials would ultimately lead to major contributions to the mobility and and quality of life for these patients. Considerable effort has been devoted to alter surface characteristics of orthopaedic implants to improve the interlocking of device and skeleton. We were the first to demonstrate that surface chemical modification of biomaterials using selected ions resulted in an enhanced bone formation. This proposal is aimed at chemically modifying the surfaces of commonly used orthopaedic and dental materials, to improve the biocompatibility of new devices and the surface coatings for existing prostheses. Furthermore, this application will build on the in vitro data showing that particular peptides specifically bind osteoblasts and therefore have the potential to provide a surface on a prosthesis that is conducive to bone formation. To date, we have coupled these peptides to metallic surfaces and will proceed to study the osteoblastic phenotype and subsequent osteogenesis. Development of these novel biocompatible surfaces is anticipated to reduce patient morbidity and result in significant health care savings.Read moreRead less
Solid phase synthesis of side-chain cross-linked peptide oligomers. This research will provide a unique opportunity to investigate the biological pathways and causative factors leading to diseases such as Alzheimer’s disease. Such information will guide the design and development of therapeutic strategies and diagnostic reagents.
Development Of A Generic Strategy For The Stabilisation Of Peptide-based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$443,196.00
Summary
There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides the ....There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides therapeutically promising peptides and proteins the ability to resist the body s natural degradation pathways so they are able to reach their biological target. To develop this strategy we will use the recently discovered peptide hepcidin as a model system. Hepcidin is the major iron-regulatory hormone in the human body and incorrect levels of this hormone result in either iron overload (haemochromatosis), when there is not enough hepcidin produced by the body, or anemia of inflammation when there is too much hepcidin. The development of hepcidin-based therapeutic agents to treat these conditions has the potential to have significant impact as it has been estimated that up to 1 in 300 Australians are affected by haemochromatosis during their lifetimes. Unfortunately, unmodified peptides, like hepcidin, are of limited therapeutic value due to their poor stability within the human body. This research proposal describes the development of stabilised hepcidin analogues with the potential of being useful drug leads for the treatment of haemochromatosis.Read moreRead less
The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. ....The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. We anticipate that there will be patents that will ensue from the programme, which will be licensed to Australian interests, and contribute to the national revenue in the biotechnology and pharmaceutical sector.Read moreRead less
Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins ....Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins central to AD, including amyloid-beta, and their role in AD development. Upon completion of this project, we expect to better understand neural copper metabolism in health and in AD pathology, with outcomes directly applicable to therapeutic AD intervention.Read moreRead less
The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between ....The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between plasma proteins and apoE, which is a lipid-binding protein genetically linked to age-related diseases affecting more than 500,000 Australians. This project will therefore provide scope for novel treatments and early detection of disease, namely cardiovascular and Alzheimer's disease.Read moreRead less
Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The m ....Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The markers may also be used to monitor the disease progress and the effects of treatment. The results from this study may improve the prognosis of CaP patients.Read moreRead less
Identification of novel biomarkers for diabetic retinopathy in tears. There are around 134,000 people with diabetic retinopathy in Australia. The disease affects patients' physical and mental state and economical and social cost is enormous. This research aims to find new biomarkers for the disease which may lead to better treatment and management. Patient's quality of life may be significantly improved by early diagnosis and treatment and the burden to the community reduced. This project also g ....Identification of novel biomarkers for diabetic retinopathy in tears. There are around 134,000 people with diabetic retinopathy in Australia. The disease affects patients' physical and mental state and economical and social cost is enormous. This research aims to find new biomarkers for the disease which may lead to better treatment and management. Patient's quality of life may be significantly improved by early diagnosis and treatment and the burden to the community reduced. This project also gives industrial partners the opportunity to develop new products to diagnose and monitor the disease.Read moreRead less
Relaxin family peptides are small proteins that have numerous essential biological roles in the vascular system, brain and gut. The hormone relaxin is currently in Phase III clinical trials to treat heart failure and the other peptides show great potential as drugs to treat diseases including mental illnesses and obesity. My research focuses on developing drugs targeting the receptors for these important peptide systems and understanding how these drugs can be best used therapeutically