The Development Of Selective And Potent Kv1.3 Ion Channel Blockers For The Treatment Of Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$233,187.00
Summary
Building on the well-established path of developing drugs from Nature, the amplification of some unusual qualities of a naturally-occurring substance, khellinone, could lead to new treatments for autoimmune diseases such as multiple sclerosis and diabetes. Designed variants of khellinone are known to be very effective at preventing the destructive impact of the body's own T cells on the central nervous system that occurs in autoimmune disease.
The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to tes ....The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to test and identify people at risk for type 1 diabetes. They showed that the underlying disease could start years before symptoms occurred and discovered genes that determine the rate at which the underlying disease progresses. They have also found evidence that the disease may be triggered by gut viruses called rotaviruses in genetically-susceptible individuals. They showed that type 1 diabetes could be prevented in a mouse model by getting the immune system to make a protective response to insulin, and then went on to apply this in at-risk humans in a controlled trial of intranasal insulin, the first of its kind. They have used genetic techniques not only to pinpoint the mechanisms responsible for killing the beta cells but also to modify the beta cells to make them resistant to attack by these mechanisms. The multidisciplinary approach of the team will be directed to further understanding the genetic and environmental factors underlying type 1 diabetes and the immune mechanisms, particularly involving special white blood cells called T cells, that kill beta cells. A molecular target of the immune attack, the parent of insulin called proinsulin, will be used, paradoxically, as a tool to regulate the immune system and avert the attack. This will be achieved by giving proinsulin via the mucosa of the naso-respiratory tract or via the bone marrow-derived stem cells, initiallyin the mouse model as a test of feasibility for human application. In parallel with these approaches to prevention, specially constructed viruses will be used to transfer several new genes into beta cells to improve their resistance to immune attack, so that they can be transplanted into people with established diabetes without the need for potentially toxic drugs that suppress the immune system overall. The integrated research of the team is helping to provide a sound, rational base for the eventual prevention and cure of type 1 diabetes.Read moreRead less
My research is directed to the prevention of type 1 diabetes, based on understanding immune-inflammatory mechanisms that contribute to dysfunction of insulin-secreting beta cells and tissue resistance to the action of insulin. I study these mechanisms in rodent models and in humans with the aim of manipulating them for therapeutic benefit. I am particularly interested in understanding environment-gene interactions mediated by epigenetic modifications.
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new treatments.
Analysis Of Human CD4+ T-cell Responses To Epitopes Formed By Peptide Fusion In The Pathogenesis Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,239,989.00
Summary
Type 1 diabetes is caused by immune-mediated destruction of the insulin-secreting beta cells. Recently we discovered new targets ‘seen’ by the immune system that may explain why the immune system causes type 1 diabetes. Here we will determine if responses to these targets cause type 1 diabetes. This is important because it tests a new idea and our results will have a major impact on efforts to develop new therapies for type 1 diabetes an other autoimmune diseases.