Genetic Bases For Charcot-Marie-Tooth And Hereditary Sensory Type 1 Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$618,055.00
Summary
This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradua ....This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradually increasing disability eventually requiring splints and other walking aids. We propose to use the newly developed resources of the human genome project to locate the defective gene. In previous studies we have used these methods to locate the defective genes of 2 other hereditary diseases of nerve. In this study we propose to investigate a newly recognised form of CMT called intermediate CMT. Intermediate CMT has characteristics intermediate between the better known forms of CMT affecting the nerve itself (the axon) or the nerve insulation (the surrounding myelin sheath). The disorder may therefore affect both components of nerve. The affected gene may mediate communication between the nerve and its sheath. This research should give valuable insight into the mechanisms responsible for the maintenance of normal nerve. Finding the gene may therefore have relevance to many other diseases of nerve. This research is a systematic search and should lead to the abnormal gene causing the disease. Once the gene involved is known then an effective test will be developed. When we can test for the disease, we probably will find that the disorder is much more common than previously recognised. Knowledge of the function of this gene will lead to an understanding of how the disease develops and will eventually lead to effective treatments.Read moreRead less
NEU-HORIZONS: The Neuroprotection And Therapeutic Use Of Riluzole For The Prevention Of Oxaliplatin Neurotoxicity Study.
Funder
National Health and Medical Research Council
Funding Amount
$382,402.00
Summary
Colorectal cancer is the second most commonly diagnosed cancer in Australia, with more than 13500 cases recorded annually. Oxaliplatin is an effective chemotherapy for the treatment of colorectal cancer. The major side-effect of oxaliplatin is the development of nerve damage that leads to loss of feeling in the hands and feet and significant disability. The aim of this study is to conduct a trial of a new treatment for oxaliplatin-induced nerve damage.
After The Cloning Of The HMSNL Gene: Molecular Pathogenesis Of The Disease
Funder
National Health and Medical Research Council
Funding Amount
$258,564.00
Summary
We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in th ....We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in the basic mechanisms of interaction between the two main types of cell in the peripheral nervous system: the myelin-producing Schwann cell and the neuron. The two cells form the most complex system of communication in the human body, where signaling from one is vital for the development, functioning and survival of the other. Very little is known about the molecular mechanisms of this communication. At the same time, knowledge of the normal mechanisms of interaction is the key to better understanding of the mechanisms of disease in the peripheral nervous system and of the causes and possible prevention of the impairment of function. The newly identified HMSNL gene is probably involved in the signaling necessary for the development and functioning of the Schwann cell and for the survival of the nerve fibres. To gain an insight into the nature of the signaling cascade, we propose to use several complementary experimental approaches. We will create a mouse model of the human disease, to study its very early stages and subsequent evolution. In parallel, we will use molecular techniques and a yeast model, to identify other steps in the signaling cascade. The NHMRC-funded study will be part of a larger project conducted in collaboration with leading laboratories in the UK and the Netherlands, where other aspects of the molecular basis of the disease and of the role of the new gene will be examined.Read moreRead less
How Amyloid Causes Neurodegeneration: The Role Of Transthyretin In Familial Amyloidotic Polyneuropathy
Funder
National Health and Medical Research Council
Funding Amount
$618,950.00
Summary
This project seeks to understand the biochemical basis of nerve degeneration in a disease known as familial amyloidotic polyneuropathy. This disease is caused by a protein known as transthyretin, which is abnormally deposited around nerves and causes nerve damage. The project is highly likely to provide clues which help us understand some related dementia causing diseases like Alzheimer's disease and prion diseases such as scrapie and mad cow disease.
The Incidence And Predictors Of Foot Disease Hospitalisation
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Foot disease seems to be a much larger cause of hospitalisation than first thought. This research program aims to study for the first ever time the annual incidence of foot disease hospitalisation and develop models to predict which patients with foot disease are likely to be hospitalised or die. We believe this research will help clinicians, researchers and governments from around the world to measure, predict and prevent foot disease hospitalisation in their nations for the first time.
Enhanced Sensory Perception Via Jitter Reduction And Neural Synchronisation Evoked By Subsensory Electrical Noise Stimulation – Restoring Sensitivity In Peripheral Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$318,473.00
Summary
The elderly and patients with diabetes are at high risk of losing sensation in their feet and currently no treatment for this condition exists. This loss of feeling leads to falls, fractures and foot ulcers, which in many cases end with amputation. We have developed a new subsensory stimulation technique which for the first time restores lost sensation. Development of this novel treatment is made possible by a multi-disciplinary team of engineers, neuroscientists, physiologists and podiatrists.
A Novel Sensory Nerve Stimulator To Improve Neuropathy In Patients With Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$407,924.00
Summary
We have developed a painless, self-applied, cheap, battery powered electrical stimulation treatment that improves sensory nerve function in some people with diabetic peripheral neuropathy. We have tested this technique in laboratory animals and in people with diabetes and have shown it is effective in some. We now propose to test this technique in a large sample of people similar to the participants in the successful group of our pilot study - 55-65 year old people with diabetes of shorter durat ....We have developed a painless, self-applied, cheap, battery powered electrical stimulation treatment that improves sensory nerve function in some people with diabetic peripheral neuropathy. We have tested this technique in laboratory animals and in people with diabetes and have shown it is effective in some. We now propose to test this technique in a large sample of people similar to the participants in the successful group of our pilot study - 55-65 year old people with diabetes of shorter duration. In addition, older people up to 75 years of age, with up to 10 years duration of diabetes will be included separately. If successful, the electrical stimulation could improve sensation leading to fewer ulcerations and amputations. Much suffering and expense would be avoided. - The magnitude of reduction in suffering and expense can be judged from the fact that people with diabetes have 15 times the risk of amputation as do people without diabetes. In Australia half of non-traumatic amputations are done to people with diabetes. Foot ulcers precede amputations in most cases, and in themselves cause much suffering and expense. Australia needs to act on this now because, if current trends continue, the number of people with diabetes will increase as the population ages. -The number of people aged over 65 will increase from around 2.3 million at present to over 6 million in the next half century. The increase in those over 85 will be even more marked with numbers increasing four fold to over one million people. Diabetes affects approximately 23% of people aged 75 or older.Read moreRead less
Transcriptional Regulation Of Nociceptor Function And Extreme Genetic Pain Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,007,462.00
Summary
Disorders involving untreatable pain have a devastating impact on a patient’s quality of life. To better treat these conditions, we require a basic understanding of how sensory neurons work. In this study we will define the genetic network involved in regulating pain-sensing neurons. We will then search the genome of pain patients looking for coding mutations within this pain transcriptional network, and we will prove these mutations are causative in fly and mouse systems.