Predicting Treatment Response To Onabotulinumtoxin-a In MS-related Tremor: A Combined Clinical, Electrophysiological And Neuroimaging Approach.
Funder
National Health and Medical Research Council
Funding Amount
$546,359.00
Summary
Shaking (tremor) of the upper limbs occur in many people with multiple sclerosis (MS). We have previously shown that botulinum toxin (Botox) injections could help reduce tremor. This study aims to study the effect of Botox in a larger group of people with MS and will include detailed MRI scans and electrical tremor monitoring tests to define the underlying changes in the brain that causes tremor. The results will help make Botox available as a tremor treatment for people with MS.
Tremor And Cognition In Multiple Sclerosis: Implementing Novel Treatments And Computerized Monitoring Strategies.
Funder
National Health and Medical Research Council
Funding Amount
$303,014.00
Summary
This research program aims to study two disabling symptoms of multiple sclerosis namely upper limb shaking, or tremor, and memory dysfunction. The first project will develop a new treatment for MS arm tremor, Botulinum toxin injections, into routine clinical practice. The second project aims to make available a computerised test of memory that can be done in clinic waiting rooms or at home. This will help neurologists to rapidly pick up changes in memory in a person with MS and improve care.
An RCT To Determine The Optimum Frequency Of Botulinum Toxin Injections To The Calf In Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$286,358.00
Summary
Cerebral Palsy (CP) is the most common cause of disability amongst children across the developed world. There are about 1800 children with CP in Victoria alone. It is caused by damage to the brain in early childhood. Children with CP have difficulty controlling how their muscles work. Muscles are often spastic, which means that they are switched on all the time, and this makes walking and performing other tasks difficult. As the child grows the spastic muscles can become too short and this occur ....Cerebral Palsy (CP) is the most common cause of disability amongst children across the developed world. There are about 1800 children with CP in Victoria alone. It is caused by damage to the brain in early childhood. Children with CP have difficulty controlling how their muscles work. Muscles are often spastic, which means that they are switched on all the time, and this makes walking and performing other tasks difficult. As the child grows the spastic muscles can become too short and this occurs can only be corrected by orthopaedic surgery. The spasticity in particular muscles can be reduced by injecting them with Botulinum Toxin (commonly known as Botox and used cosmetically to remove wrinkles). The effects of a single injection have been closely studied and we know that the effect of the toxin wears off. Children are thus offered repeat injections but there have been no studies to investigate what is the most appropriate interval between injections. The aim of this study is to determine this. In routine clinical practice children tend to get injections approximately once a year. A consideration of what we know about how the toxin acts, however, suggests that injections every 4 months might be expected to be more effective. This study will thus randomly allocate children to receive injections either every twelve months or every four months over a two year period. During the study both groups will be monitored to see if there are differences in how easily they can walk and perform other functions and in their overall quality of life. After the study the children will also be assessed to see whether there is any difference in the length of the spastic muscles. There have been no other studies to investigate the most appropriate interval between injections. This study will thus be the first anywhere and will be the foundation for guidelines for the ongoing use of botulinum toxin in children with cerebral palsy in Australia and throughout the world.Read moreRead less
Gene Therapy To Cure Botulinum Toxin Intoxication And New Motoneuron Delivery System
Funder
National Health and Medical Research Council
Funding Amount
$390,321.00
Summary
The aim of the project is to establish two biotechnological strategies to help curing motoneuronal diseases. Botulinum neurotoxins (BoNTs) are the deadliest toxins known. They provoke profound flaccid neuromuscular paralysis that leads to death due to respiratory failure. There are no current therapies available and affected patients require respiratory assistance for up to 7 months with sophisticated respirators. BoNT is therefore an acquired motoneuronal disease and a well-known biological wea ....The aim of the project is to establish two biotechnological strategies to help curing motoneuronal diseases. Botulinum neurotoxins (BoNTs) are the deadliest toxins known. They provoke profound flaccid neuromuscular paralysis that leads to death due to respiratory failure. There are no current therapies available and affected patients require respiratory assistance for up to 7 months with sophisticated respirators. BoNT is therefore an acquired motoneuronal disease and a well-known biological weapon which is also easy to produce in large quantities. It is therefore important to provide a quick and efficient way of overriding BoNT-induced paralysis other than very costly mechanical respirators. Our first strategy aims at designing a gene therapy against botulism. BoNTs promote muscular paralysis by cleaving molecules implicated in the mechanism of neuronal communication (SNARE proteins). Our aim is to deliver genetically modified uncleavable forms of SNAREs to rescue neuronal communication and prevent botulism. BoNT are comprised of two chains: a toxic light chain and a non toxic heavy chain which is responsible for the extreme selectivity of BoNT for motoneurons and for delivering the light chain in the motoneuronal cytosol by a mechanism named translocation. Our second aim is to use the BoNTs atoxic heavy chain to engineer a selective motoneuronal delivery system. This could be useful in the future to deliver molecules of interest in diseased motoneurons.Read moreRead less
A Randomised Trial Of Constraint Induced Movement Therapy And Botulinum Toxin A In Children With Congenital Hemiplegia.
Funder
National Health and Medical Research Council
Funding Amount
$399,995.00
Summary
Congenital hemiplegia occurs in over 1 million children under 21 years of age in the industrialized world. It is the most common type of cerebral palsy, accounting for 36 percent of children diagnosed with this lifelong condition. We intend to determine if a promising new treatment approach is effective in providing a superior and lasting benefit, compared to conventional techniques. Children with hemiplegia usually have the intellectual capacity to attend normal school; however the impaired arm ....Congenital hemiplegia occurs in over 1 million children under 21 years of age in the industrialized world. It is the most common type of cerebral palsy, accounting for 36 percent of children diagnosed with this lifelong condition. We intend to determine if a promising new treatment approach is effective in providing a superior and lasting benefit, compared to conventional techniques. Children with hemiplegia usually have the intellectual capacity to attend normal school; however the impaired arm reduces independence in activities of daily living and can compromise their ability to participate in educational, leisure and vocational roles. Previously we have shown that a program of upper limb rehabilitation in children with spasticity was effective in improving participation and quality of life. We have also shown that rehabilitation combined with Botulinum toxin A (Botox) can further improve functional activity. We believe that a new method of therapy, that has been used effectively in Adults with stroke, called Constraint Induced Movement Therapy (CIMT) may also be beneficial in the treatment of children with congenital hemiplegia. In CIMT, the unimpaired arm is constrained in a glove to promote use of the impaired arm (hemiplegic arm). We predict that, combined with the Botox treatment, CIMT will provide a superior and longer lasting benefit compared to standard rehabilitation combined with Botox. The primary aim of our study is to test this hypothesis in a controlled trial. A secondary aim is to further our understanding of the central neurovascular mechanisms underlying changes in upper limb function. To achieve this, we will use Functional Magnetic Resonance Imaging (fMRI) and Transcranial Magnetic Stimulation (TMS) to measure central activation in the parts of the brain controlling movement. Improving our understanding of the mechanisms involved in this condition is an essential next step towards providing a more effective and long lasting treatment.Read moreRead less
Pre-clinical Development Of A Chemically Synthetic Anti-toxic Vaccine Against Malaria
Funder
National Health and Medical Research Council
Funding Amount
$165,000.00
Summary
Plasmodium falciparum malaria infects 5-10% of the global population (400 million clinical cases) and kills two million people annually1. As such it ranks along with HIV and TB as the most serious infectious disease of humanity. It is widely accepted that an efficacious vaccine is required to afford protection against malarial fatalities. The induction of broad-ranging sterilizing immunity is not considered a likely objective for anti-malarial vaccines. Instead, reduction in morbidity and mortal ....Plasmodium falciparum malaria infects 5-10% of the global population (400 million clinical cases) and kills two million people annually1. As such it ranks along with HIV and TB as the most serious infectious disease of humanity. It is widely accepted that an efficacious vaccine is required to afford protection against malarial fatalities. The induction of broad-ranging sterilizing immunity is not considered a likely objective for anti-malarial vaccines. Instead, reduction in morbidity and mortality is the realistic aim of malaria vaccine strategies. Traditional approaches seek to provide this clinical protection indirectly, by killing the parasite or by reducing parasite multiplication. To this end, current anti-malarial vaccines candidates seek to confer on the host parasiticidal immune mechanisms, which have as their target antigenic proteins expressed on the surface of the different stages of the parasite. No malaria vaccine is yet on the market. There exist several potentially competitive leads in late-stage pre-clinical-early stage clinical development, particularly recombinant proteins. The US Navy MUSTDO-25 DNA vaccines are not living up to their promise. Most leading “vaccine candidates” are polymorphic alleles. There are significant prospects for vaccine-induced selection of breakthrough variants. Multiple alleles may also prove cost-prohibitive for vaccine development. The novelty and uniqueness of this approach have contributed to the acceptance of this study for publication by Nature. The aims of this proposal are four-fold: i) to further rationalize the target through chemical synthesis of intermediates and partial structures; (ii) to examine antigenicity and immunogenicity in large experimental mammals, and undertake epitope mapping of human anti-GPI IgG responses; (iii) to obtain preliminary safety data in these animals; and (iv) to undertake a vaccine trial in a simian malaria model. We envisage objectives (i)-(iii) will take 12 months. Objective (iv) will proceed in the six months thereafter.Read moreRead less
Factors Affecting The Toxicity Of The Dinoflagellate, Gambierdiscus Toxicus, And The Development Of Ciguatera Outbreaks
Funder
Fisheries Research and Development Corporation
Funding Amount
$22,600.00
Summary
Objectives: 1. Define factors influencing ciguatoxin production by cultures of Gambierdiscus toxicus. 2. Examine reef disturbance effects & significance of genetic heterogeneity in G. toxicus in toxin production. 3. Establish requirements for growth & bloom formation by G. toxicus & other dinoflagellates