Posts tagged treatment
Articles and news from the latest research reports.
Possible new approach to fighting chronic inflammatory diseases
30 July 2012
Researchers from The University of Queensland’s Institute for Molecular Bioscience have discovered a potential new approach to treating chronic inflammatory diseases such as arthritis.
Professor David Fairlie and his colleagues have developed an experimental treatment that has proven effective at reducing symptoms and stopping the progression of the disease in models of arthritis.
“Human enzymes called proteases stimulate the secretion of immune cells that, when the correct amount is released, play important roles in digestion, fighting infections and healing wounds,” Professor Fairlie said.
“But in chronic inflammatory diseases such as arthritis, these enzymes continuously stimulate the release of immune cells, which cause inflammation when present at high levels. This leads to ongoing tissue damage.”
Professor Fairlie and his team have developed experimental compounds that block this stimulation and successfully reduce chronic inflammatory arthritis in experimental models.
If the treatment could be transferred to humans, it has the potential to reduce both the health and economic impacts of chronic inflammatory diseases.
Almost four million Australians suffer from chronic joint pain and disability caused by various forms of arthritis, including osteoarthritis, rheumatoid arthritis and gout.
Related healthcare and loss of employment cost Australia over $20 billion per year, an amount that is expected to increase dramatically as our population ages.
These promising new findings are published in the current hard-copy edition of The Federation of American Societies For Experimental Biology Journal, the world’s most cited scientific journal in biology.
Journal subscribers can access the paper at this address: http://bit.ly/Pg8lgk
Source: The University of Queensland
Finding a druggable target for schizophrenia
Schizophrenia is a devastating brain disease that affects ∼1% of the population worldwide and is characterized by a complex array of positive (delusions and hallucinations), negative (apathy and social withdrawal), and cognitive (deficits in attention and working memory) symptoms. Clinical features of schizophrenia frequently arise during late adolescence or early adulthood, which places this disease as the most chronic of the psychotic disorders and as one of the leading causes of disability and premature mortality (1). Increasing evidence suggests that cognitive impairment is at the core of schizophrenia and precedes the manifestation of psychosis (2). Furthermore, no pharmacological treatment is currently available for cognitive deficits, which are among the most debilitating symptoms of the disorder. The identification of novel treatments to ameliorate the cognitive symptoms of schizophrenia thus seems crucial to improve the quality of life in these patients.
Brain discovery sheds light on link between vision and emotion
Neuroscientists have discovered a new area of the brain that is uniquely specialised for peripheral vision and could be targeted in future treatments for panic disorders and Alzheimer’s disease.
Published today in high impact journal Current Biology, researchers led by Dr Hsin-Hao Yu and Professor Marcello Rosa from Monash University’s Department of Physiology found that a brain area, known as prostriata, was specialised in detecting fast-moving objects in peripheral vision.
This area, located in a primitive part of the cerebral cortex, has characteristics unlike any other visual area described before, including a “direct line” of communication to brain areas controlling emotion and quick reactions.
Dr Yu said the discovery, identified during the development of the Monash Vision Group’s bionic eye, funded through the ARC Research in Bionic Vision Science and Technology Initiative, could lead to new treatments for panic disorders such as agoraphobia (fear of open spaces) and may extend into other medical areas including Alzheimer’s treatment.
“The brain is the most complex organ in the human body and perhaps the most remarkable. These findings change how we think of the brain in terms of how visual information is processed,” Dr Yu said.
“This area is likely to be hyperactive in panic disorder, with agoraphobia. This knowledge could lead to treatment options for the hyperactivity, and therefore sensitivity to such disorders, particularly the fear of open spaces.
“Correlation with previous studies also shows that prostriata is one of the first areas affected in Alzheimer’s disease. This knowledge helps to explain spatial disorientation and the tendency to fall, which are among the earliest signs of a problem associated with Alzheimer’s.”
Professor Rosa said this area had ultra-fast responses to visual stimuli, simultaneously broadcasting information to brain areas that control attention, emotional and motor reactions. This challenges current conceptions of how the brain processes visual information.
“This suggests a specialised brain circuit through which stimuli in peripheral vision can be fast-tracked to command quickly coordinated physical and emotional responses,” Professor Rosa said.
Powerful class of antioxidants may be potent Parkinson’s treatment
JUL 23, 2012
A new and powerful class of antioxidants could one day be a potent treatment for Parkinson’s disease, researchers report.
Dr. Bobby Thomas
A class of antioxidants called synthetic triterpenoids blocked development of Parkinson’s in an animal model that develops the disease in a handful of days, said Dr. Bobby Thomas, neuroscientist at the Medical College of Georgia at Georgia Health Sciences University and corresponding author of the study in the journal Antioxidants & Redox Signaling.
Thomas and his colleagues were able to block the death of dopamine-producing brain cells that occurs in Parkinson’s by using the drugs to bolster Nrf2, a natural antioxidant and inflammation fighter.
Stressors from head trauma to insecticide exposure to simple aging increase oxidative stress and the body responds with inflammation, part of its natural repair process. “This creates an environment in your brain that is not conducive for normal function,” Thomas said. “You can see the signs of oxidative damage in the brain long before the neurons actually degenerate in Parkinson’s.”
Nrf2, the master regulator of oxidative stress and inflammation, is – inexplicably – significantly decreased early in Parkinson’s. In fact, Nrf2 activity declines normally with age.
“In Parkinson’s patients you can clearly see a significant overload of oxidative stress, which is why we chose this target,” Thomas said. “We used drugs to selectively activate Nrf2.”
They parsed a number of antioxidants already under study for a wide range of diseases from kidney failure to heart disease and diabetes, and found triterpenoids the most effective on Nrf2. Co-author Dr. Michael Sporn, Professor of Pharmacology, Toxicology and Medicine at Dartmouth Medical School, chemically modified the agents so they could permeate the protective blood-brain barrier.
Both in human neuroblastoma and mouse brain cells they were able to document an increase in Nrf2 in response to the synthetic triterpenoids. Human dopaminergic cells are not available for research so the scientists used the human neuroblastoma cells, which are actually cancer cells that have some properties similar to neurons.
Their preliminary evidence indicates the synthetic triterpenoids also increase Nrf2 activity in astrocytes, a brain cell type which nourishes neurons and hauls off some of their garbage. The drugs didn’t protect brain cells in an animal where the Nrf2 gene was deleted, more proof that that Nrf2 is the drugs’ target.
The researchers used the powerful neurotoxin MPTP to mimic Parkinson’s-like brain cell damage in a matter of days. They are now looking at the impact of synthetic triterpenoids in an animal model genetically programmed to acquire the disease more slowly, as humans do. Collaborators at Johns Hopkins School of Medicine also will be providing induced pluripotent stem cells, adult stem cells that can be coaxed into forming dopaminergic neurons, for additional drug testing.
Other collaborators include scientists at Weill Medical College of Cornell University, Johns Hopkins School of Public Health, Moscow State University, Tohoku University and the University of Pittsburgh.
Source: EarthSky
New epilepsy gene identified; possible new treatment option
ScienceDaily (July 23, 2012) — New research conducted by neuroscientists from the Royal College of Surgeons in Ireland (RCSI) published in Nature Medicine has identified a new gene involved in epilepsy and could potentially provide a new treatment option for patients with epilepsy.
The research focussed on a new class of gene called a ‘microRNA’ which controls protein production inside cells. The research looked in detail at one particular microRNA called ‘microRNA-134’ and found that levels of microRNA-134 are much higher in the part of the brain that causes seizures in patients with epilepsy.
By using a new type of drug-like molecule called an antagomir which locks onto the ‘microRNA-134’ and removes it from the brain cell, the researchers found they could prevent epileptic seizures from occurring.
Professor David Henshall, Department of Physiology & Medical Physics, RCSI and senior author on the paper said ‘We have been looking to find what goes wrong inside brain cells to trigger epilepsy. Our research has discovered a completely new gene linked to epilepsy and it shows how we can target this gene using drug-like molecules to reduce the brain’s susceptibility to seizures and the frequency in which they occur.”
Dr Eva Jimenez-Mateos, Department of Physiology & Medical Physics, RCSI and first author on the paper said “Our research found that the antagomir drug protects the brain cells from toxic effects of prolonged seizures and the effects of the treatment can last up to one month.”
Epilepsy affects 37,000 in Ireland alone. For every two out of three people with epilepsy their seizures are controlled by medication, but one in three patients continues to have seizures despite being prescribed medication. This study could potentially offer new treatment methods for patients.
The research was supported by a grant from Science Foundation Ireland (SFI). Researchers in the Department of Physiology & Medical Physics and Molecular & Cellular Therapeutics, RCSI, clinicians at Beaumont Hospital and experts in brain structure from the Cajal Institute in Madrid were involved in the study.
Source: Science Daily
Stanford researchers produce first complete computer model of an organism
A mammoth effort has produced a complete computational model of the bacterium Mycoplasma genitalium, opening the door for biological computer-aided design.
In a breakthrough effort for computational biology, the world’s first complete computer model of an organism has been completed, Stanford researchers reported last week in the journal Cell.
A team led by Markus Covert, assistant professor of bioengineering, used data from more than 900 scientific papers to account for every molecular interaction that takes place in the life cycle of Mycoplasma genitalium, the world’s smallest free-living bacterium.
By encompassing the entirety of an organism in silico, the paper fulfills a longstanding goal for the field. Not only does the model allow researchers to address questions that aren’t practical to examine otherwise, it represents a stepping-stone toward the use of computer-aided design in bioengineering and medicine.
"This achievement demonstrates a transforming approach to answering questions about fundamental biological processes," said James M. Anderson, director of the National Institutes of Health Division of Program Coordination, Planning and Strategic Initiatives. "Comprehensive computer models of entire cells have the potential to advance our understanding of cellular function and, ultimately, to inform new approaches for the diagnosis and treatment of disease."
The research was partially funded by an NIH Director’s Pioneer Award from the National Institutes of Health Common Fund.
Anti-Tau Drug Improves Cognition, Decreases Tau Tangles in Alzheimer’s Disease Models
ScienceDaily (July 19, 2012) — While clinical trial results are being released regarding drugs intended to decrease amyloid production — thought to contribute to decline in Alzheimer’s disease — clinical trials of drugs targeting other disease proteins, such as tau, are in their initial phases.
Penn Medicine research presented July 19 at the 2012 Alzheimer’s Association International Conference (AAIC) shows that an anti-tau treatment called epithilone D (EpoD) was effective in preventing and intervening the progress of Alzheimer’s disease in animal models, improving neuron function and cognition, as well as decreasing tau pathology.
By targeting tau, the drug aims to stabilize microtubules, which help support and transport of essential nutrients and information between cells. When tau malfunctions, microtubules break and tau accumulates into tangles.
"This drug effectively hits a tau target by correcting tau loss of function, thereby stabilizing microtubules and offsetting the loss of tau due to its formation into neurofibrillary tangles in animal models, which suggests that this could be an important option to mediate tau function in Alzheimer’s and other tau-based neurodegenerative diseases," said John Trojanowski, MD, PhD, professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. "In addition to drugs targeting amyloid, which may not work in advanced Alzheimer’s disease, our hope is that this and other anti-tau drugs can be tested in people with Alzheimer’s disease to determine whether stabilizing microtubules damaged by malfunctioning tau protein may improve clinical and pathological outcomes."
The drug, identified through Penn’s Center for Neurodegenerative Disease Research (CNDR) Drug Discovery Program, was previously shown to prevent further neurological damage and improve cognitive performance in animal models*. The Penn research team includes senior investigator Bin Zhang, MD, and Kurt Brunden, PhD, director of Drug Discovery at CNDR.
Bristol-Myers Squibb, who developed and owns the rights to the drug, has started enrolling patients into a phase I clinical trial in people with mild Alzheimer’s disease.
Source: Science Daily
Research shows nerve stimulation can reorganize brain
July 19, 2012 By Emily Martinez
(Medical Xpress) — UT Dallas researchers recently demonstrated how nerve stimulation paired with specific experiences, such as movements or sounds, can reorganize the brain. This technology could lead to new treatments for stroke, tinnitus, autism and other disorders.
Dr. Michael Kilgard helped lead a team that paired vagus nerve stimulation with physical movement to improve brain function.
In a related paper, UT Dallas neuroscientists showed that they could alter the speed at which the brain works in laboratory animals by pairing stimulation of the vagus nerve with fast or slow sounds.
A team led by Dr. Robert Rennaker and Dr. Michael Kilgard looked at whether repeatedly pairing vagus nerve stimulation with a specific movement would change neural activity within the laboratory rats’ primary motor cortex. To test the hypothesis, they paired the vagus nerve stimulation with movements of the forelimb in two groups of rats. The results were published in a recent issue of Cerebral Cortex.
After five days of stimulation and movement pairing, the researchers examined the brain activity in response to the stimulation. The rats who received the training along with the stimulation displayed large changes in the organization of the brain’s movement control system. The animals receiving identical motor training without stimulation pairing did not exhibit any brain changes, or plasticity.
People who suffer strokes or brain trauma often undergo rehabilitation that includes repeated movement of the affected limb in an effort to regain motor skills. It is believed that repeated use of the affected limb causes reorganization of the brain essential to recovery. The recent study suggests that pairing vagus nerve stimulation with standard therapy may result in more rapid and extensive reorganization of the brain, offering the potential for speeding and improving recovery following stroke, said Rennaker, associate professor in The University of Texas at Dallas’ School of Behavioral and Brain Sciences.
“Our goal is to use the brain’s natural neuromodulatory systems to enhance the effectiveness of standard therapies,” Rennaker said. “Our studies in sensory and motor cortex suggest that the technique has the potential to enhance treatments for neurological conditions ranging from chronic pain to motor disorders. Future studies will investigate its effectiveness in treating cognitive impairments.”
Discovery May Lead to New Treatment for ALS
ScienceDaily (July 18, 2012) — Researchers at Oregon Health & Science University School of Dentistry have discovered that TDP-43, a protein strongly linked to ALS (amyotrophic lateral sclerosis) and other neurodegenerative diseases, appears to activate a variety of different molecular pathways when genetically manipulated. The findings have implications for understanding and possibly treating ALS and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
ALS affects two in 100,000 adults in the United States annually and the prognosis for patients is grim.The new discovery is published online in G3: Genes, Genomes, Genetics (and the July 2012 print issue of G3).
Using a fruit fly model, the OHSU team genetically increased or eliminated TDP-43 to study its effect on the central nervous system. By using massively parallel sequencing methods to profile the expression of genes in the central nervous system, the team found that the loss of TDP-43 results in widespread gene activation and altered splicing, much of which is reversed by rescue of TDP-43 expression. Although previous studies have implicated both absence and over expression of TDP-43 in ALS, the OHSU study showed little overlap in the gene expression between these two manipulations, suggesting that the bulk of the genes affected are different.
"Our data suggest that TDP-43 plays a role in synaptic transmission, synaptic release and endocytosis," said Dennis Hazelett, Ph.D., lead author of the study. "We also uncovered a potential novel regulation of several pathways, many targets of which appear to be conserved."
Source: Science Daily
AAN: New guideline on how to best treat involuntary movements in Huntington’s disease
July 18, 2012
A new guideline released by the American Academy of Neurology recommends several treatments for people with Huntington’s disease who experience chorea—jerky, random, uncontrollable movements that can make everyday activities challenging. The guideline is published in the July 18, 2012, online issue of Neurology.
"Chorea can be disabling, worsen weight loss and increase the risk of falling," said guideline lead author Melissa Armstrong, MD, MSc, with the University of Maryland Department of Neurology and a member of the American Academy of Neurology.
Huntington’s disease is a complex disease with physical, cognitive and behavioral symptoms. The new guideline addresses only one aspect of the disease that may require treatment.
The guideline found that the drugs tetrabenazine (TBZ), riluzole and amantadine can be helpful and the drug nabilone may also be considered to treat chorea. The medications riluzole, amantadine and nabilone are not often prescribed for Huntington’s disease.
"People with Huntington’s disease who have chorea should discuss with their doctors whether treating chorea is a priority. Huntington’s disease is complex with a wide range of sometimes severe symptoms and treating other symptoms may be a higher priority than treating chorea," said Armstrong.
Armstrong adds that it is important for patients to understand that their doctors may try drugs not recommended in this guideline to treat chorea. More research is needed to know if drugs such as those used for psychosis are effective; however, doctors may prescribe them on the basis of past clinical experience.
Provided by American Academy of Neurology
Source: medicalxpress.com