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Cerebrospinal fluid used to deliver therapeutics for Lou Gehrig's disease to brain
July 28, 2006Researchers from the University of California, San Diego have shown that instead of trying to deliver therapeutic agents for neurodegenerative diseases across the highly impermeable blood-brain barrier via the blood, therapeutic molecules known as antisense oligonucleotides can be delivered to the brain and spinal cord through the cerebrospinal fluid (CSF) at doses shown to slow the progression of amyotrophic lateral sclerosis (ALS), also referred to as Lou Gehrig's disease, in rats.
The aggregation of toxic proteins in the central nervous system (CNS) underlies many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and ALS. Several strategies for removing excess proteins from the brain have been tried, but few have been successful due to the impermeability of the protective blood-brain barrier, which prevents substances in the blood from entering brain tissue. In a study in rats appearing online on July 27 in advance of print publication in the August issue of the Journal of Clinical Investigation, Timothy Miller, Richard Smith, and colleagues delivered effective doses of antisense oligonucleotides throughout all brain regions affected in the major neurodegenerative diseases and to all levels of the spinal cord through the CSF. Once produced, CSF circulates from the brain to all regions of the CNS, yielding complete replacement 3 times a day. Exploiting this process and using second-generation oligonucleotides with enhanced tolerability and potency, the authors were able to modulate and deliver effective doses of antisense oligonucleotides. Antisense oligonucleotides to the enzyme superoxide dismutase reduced protein and mRNA levels in the CNS. Delivery of antisense therapy initiated after the onset of symptoms slowed disease progression in a rat model of ALS. This establishes that direct delivery of antisense oligonucleotides through the CSF can be an effective means of treating neurodegenerative diseases when the appropriate toxic protein is known.
Journal of Clinical Investigation
Cerebrospinal Fluid Current Events and Cerebrospinal Fluid News RSSResearchers seeking to identify Alzheimer's risk focus on specific blood biomarker
A simple blood test to detect whether a person might develop Alzheimer's disease is within sight and could eventually help scientists in their quest toward reversing the disease's onset in those likely to develop the debilitating neurological condition.
PET scans may help assess presence of brain plaques related to Alzheimer's disease
A type of positron emission tomography (PET) scanning may be useful in a non-invasive assessment of the formation of Alzheimer's disease-related plaques in the brain, according to small study posted online today that will appear in the October 2008 print issue of Archives of Neurology, one of the JAMA/Archives journals.
Alzheimer's disease patients show improvement in trial of new drug
A new drug has been shown to improve the brain function of people with early stage Alzheimer's disease and reduce a key protein associated with the disease in the spinal fluid, in a small study published today in the journal Lancet Neurology and presented at the 2008 Alzheimer's Association International Conference on Alzheimer's Disease.
Pharmaceutical study: Less hemorrhaging after stroke, but not fewer deaths
An international study published in May 2008 in the "New England Journal of Medicine" has shown that the coagulation factor VIIa can limit the extent of a cerebral hemorrhage. However, in the long term it does not prevent death or severe impairment.
Cancer cells spread by releasing 'bubbles', according to an MUHC study
A new fundamental mechanism of how tumour cells communicate has just been discovered by the team of Dr. Janusz Rak at the Research Institute of the McGill University Health Centre (MUHC) in collaboration with Dr Guha from the University of Toronto.
Redox-active iron is a sensor of cognitive impairment associated with Alzheimer's disease
An innovative discovery has been reported that highlights the problems that oxidative stress resulting from iron cumulated in the human brain can generate in relation with the pathogenesis of Alzheimer's disease (AD), the brain disorder affecting almost 30 million throughout the world.
Scientists confirm new virus responsible for deaths of transplant recipients in Australia
In the first application of high throughput DNA sequencing technology to investigate an infectious disease outbreak, scientists from Columbia University Mailman School of Public Health, the Victorian Infectious Diseases Reference Laboratory (VIRDL) in Melbourne, Australia, the Centers for Disease Control and 454 Life Sciences link the discovery of a new arenavirus to the deaths of three transplant recipients who received organs from a single donor in Victoria, Australia in April 2007.
Scientists confirm new virus responsible for deaths of transplant recipients in Australia
In the first application of high throughput DNA sequencing technology to investigate an infectious disease outbreak, scientists from Columbia University Mailman School of Public Health, the Victorian Infectious Diseases Reference Laboratory (VIRDL) in Melbourne, Australia, the Centers for Disease Control and 454 Life Sciences link the discovery of a new arenavirus to the deaths of three transplant recipients who received organs from a single donor in Victoria, Australia in April 2007.
Protein protects brain against compound in lead poisoning, liver disease
Scientists have discovered that a protein known as PEPT2 protects the brains of mice from a naturally occurring but potentially toxic compound present in lead poisoning and in a class of liver diseases that can cause serious neurological complications.
Insulin regulates the secretion of the antiaging hormome Klotho
Dr. Carmela Abraham, a professor of biochemistry and medicine at Boston University School of Medicine (BUSM), reports this week in the Proceedings of the National Academy of Sciences new findings on Klotho, an anti-aging gene that is associated with life span extension in rodents and humans.
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