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Friday, October 24, 2014

New gene linked to blindness and Parkinson's diseases




The retinal pigment epithelium (RPE) is a tissue, which lines the back of the eye. Aging, environmental insults and genetic predispositions contribute to blindness diseases causing RPE degeneration, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
The findings, published online October 24 in The Journal of Biological Chemistry (Patil, H et al, (2014) J. Biol. Chem. 289 (43) 29767-29789) and supported by grants from the National Institutes of Health, provide a tantalizing genetic link between a multifunctional protein, called Ranbp2, and RPE degeneration and Parkinson's diseases.
The team led by Dr. Paulo A Ferreira at Duke University Medical Center, Durham, North Carolina, found that removal of Ranbp2 from the RPE in mice led to RPE degeneration with features that resemble a severe form of AMD, wet AMD.
They also pinpointed that impairment of a signaling activity of Ranbp2 that controls the flow of signaling proteins between the nuclear and cytoplasmic compartments, suffices by itself to trigger RPE degeneration. Strikingly, and like in wet AMD, such impairment of Ranbp2 caused also severe damage to neighboring blood vessels and bleeding.
Another surprising discovery was that a subset of mice without Ranbp2 in the RPE developed Parkinsonism tremors. This outcome results likely from the unexpected removal of Ranbp2 from selective brain regions controlling voluntary motor activity, an issue the authors are currently investigating.
These findings are exciting because they support that Parkinsonism and RPE degeneration share multifunctional players and they open new venues toward the development of therapeutic approaches to prevent or slow aging-related disorders, such as AMD and Parkinson's diseases.

http://www.medicalnewstoday.com/releases/284235.php

UT researchers find gene linked to Parkinson’s disease


Assistant professor Somshuvra Mukhopadhyay led a research team that discovered that an increase in Parkinson’s disease and other parkinsonian disorders can be linked to a gene mutation. Mukhopadhyay believes the understanding of the gene’s function will benefit the making of drugs that can improve gene activity.






Photo Credit: Xintong Guo | Daily Texan Staff

A University research team led by Somshuvra Mukhopadhyay, pharmacology and toxicology assistant professor, discovered that an increase in Parkinson’s disease and other parkinsonian disorders can be linked to a gene mutation.
The mutation occurs in gene SLC30A10, which helps regulate the amount of manganese in the body’s cells. The team’s study of European families with a history of hereditary parkinsonism led to the finding.“They had high levels of the metal manganese in their blood,” Mukhopadhyay said. “This suggested that the gene was required to regulate manganese levels.”
The reasearch team also determined that the gene codes for a protein that removes excess manganese from cells.It releases the amount of manganese within the cell,” Mukhopadhyay said.
The gene mutation prevents the protein from removing manganese from the cell, and it increases the amount of manganese in the blood as a result.“The gene blocked the transport of the protein, blocking the ability of the cells to transport manganese,” Mukhopadhyay said.
He also said people who have been exposed to manganese through working in the steel industry have shown a higher level of manganese in their blood.
“People who live in areas where there’s steel have a higher susceptibility to [manganese],” Mukhopadhyay said.Mukhopadhyay said the understanding of the gene’s function has implications for the development of drugs to treat people with the mutation. 
“There’s the potential to [make] drugs that can improve gene activity,” Mukhopadhyay said.Although steel workers have high exposure to manganese, Mukhopadhyay said people consume manganese through eating foods such as fish and certain vegetables.
“We get manganese from the diet,” Mukhopadhyay said.
Usually, this is not a problem, but those with the genetic mutation could accumulate too much manganese in their cells, which could become toxic.The high levels of manganese in other people, then, has indicated that they might have the mutated version of the gene.Mukhopadhyay also said environmental factors could affect the function of the gene.“In most cases, I do believe there’s a genetic factor and whole range of other factors involved,” Mukhopadhyay said.
The research team also included Michael Aschner, professor from the Albert Einstein College of Medicine, and Richard Morrisett, UT pharmacology and toxicology professor.
“Rich provided us with essential technical input on how to culture primary neurons, which was required to get this paper published,” Mukhopadhyay said in an email.

Thursday, October 23, 2014

AN AMBITIOUS STUDY OF WORLD WIDE PREVALENCE OF PARKINSON’S DISEASE


medical reseach

An Ambitious Study of World Wide Prevalence of PARKINSON’S DISEASE

In an effort to prepare public health systems to better serve future populations, a team of investigators from the University of Calgary in Alberta, Canada reviewed and analyzed over 4,000 epidemiological studies of PARKINSON’S DISEASE conducted throughout the world between the years of 1985 and 2006.  This study was part of a larger study that actually looked at 15 different neurodegenerative diseases to ensure effective planning for medical services for populations that are increasing and now include larger numbers of elderly citizens who are most affected by diseases of aging such as Alzheimer’s disease and PARKINSON’S DISEASE.  Many nations of the world will be facing health care costs for their people that will seriously strain, if not exhaust their available finances.

Although they found over 4,000 epidemiological studies from all over the world, there were many obstacles to distilling the information.  Each study had unique differences in the demographics of the participants and the methodology of the study.  Studies using only medical information did not count people who did not seek medical treatment; drug studies were also affected by cultural differences as well as the financial burdens of obtaining the medications.  Slight differences in diagnostic criteria can increase or decrease the numbers of subjects included.  Some subjects may have been misdiagnosed; others may not have had access to good medical care.  Another impediment to research on medical records is government restrictions on access to the personal data contained in those records. Overcoming these disparities in information required detailed screening of eligibility requirements to meet the standards of this study.  Ultimately, only 134 of the original 4,219 research reports met those standards.  Those were reduced even further to allow for 47 studies that were considered to meet random population sample and diagnostic criteria

The results of this study found fascinating differences in geographic distribution, age and sex.  Analysis of the data show that PARKINSON’S DISEASE is increasing worldwide, beginning with the 40 to 49 year old group, and increasing substantially in each age group.  Interestingly, in the 70 to 79 year old group there was a significant decrease (646 per 100,000 individuals) compared to Europe, North America and Australia (1,602 per 100,000 individuals).  This highest affected numbers were in the over 80 age group, with 1,903 individual per 100,000.  One reason for the higher numbers in the over 80 group may be the improvements in treatment for PARKINSON’S DISEASE as well as higher quality general care has improved chances for survival to this age and decreased mortality rates for everyone.

Division by sex showed that in all the age groups, males had only a slight increase over females.  But in the 50 to 59 age group, males had a much higher prevalence, more than three times higher than females in that same age group.   It has been suggested that estrogen in females may increase the available dopamine in the striatum that may present as a milder version of PARKINSON’S DISEASE that progresses more slowly.

While the genetics and environmental factors that lead to PARKINSON’S DISEASE are beginning to be investigated, these new studies may also have a major impact on the type and quality of medical care available to this population.  This study shows that while the world’s population is now living longer, there is also an increased prevalence in PARKINSON’S DISEASE that will require effective planning for public health care to implement resources and availability of quality care for the increased numbers of the aging population.

Pringsheim T1Jette NFrolkis ASteeves TD.; The prevalence of Parkinson’s disease: A systematic review and meta-analysis. Mov Disord. 2014 Jun 28. doi: 10.1002/mds.25945. 
http://parkinsonhope.org/ambitious-study-world-wide-prevalence-parkinsons-disease/

Gordon Buchanan, businessman and Parkinson’s advocate, dead at 85

Buchanan family invested millions in building a facility for people with Parkinson’s Disease

By Trisha Estabrooks, CBC News Posted: Oct 23, 2014 6:00 AM MT Last Updated: Oct 23, 2014 6:00 AM MT
Just months before the expected opening of the Buchanan Centre, its founder Gordon Buchanan has died.

Buchanan, 85, was diagnosed with Parkinson’s disease in 1999.
“It is heart wrenching to lose him, but his legacy will persevere,” said Brandi LaBonte with Parkinson Alberta.
“We have worked and known this great man. To quote his granddaughter ‘he was a giant,’” she said. “Not only in people's lives but within the Alberta business community and in the charitable community as well.”

‘Leave a better world’

In his obituary Buchanan is quoted as saying “if you put back just a little more than you take out, you will leave a better world.”
His final legacy will be the ‘one of a kind facility’ that will bear his name at 112th Avenue and 86th Street, across from Commonwealth Stadium.
The Buchanan Centre will be dedicated to helping people with Parkinson’s disease, a degenerative neurological disorder that affects more than 8,000 Albertans.
When it is completed, the centre will provide support for people living with Parkinson’s disease and their caregivers. The building will also become the new home for Parkinson Alberta, an organization advocating for people with the disease.
The Buchanan family bought the land and will finance the operation and maintenance for the centre.
Parkinson Alberta is hoping the province will chip in an additional $2 million to go towards costs.
Buchanon Centre
A launch was held for the Buchanan Centre in August 2013. (CBC)
The building was originally scheduled to open this summer, but LaBonte said construction delays made meeting that deadline impossible.
“It was our dream that he be the first person in, but we will make it good for him,” said Barb Foxall, the director of client services for Parkinson Alberta.
The facility is now expected to open in early 2015.

Well-known in business community

In addition to his charitable work, Buchanan was well-known in the Alberta business community, having owned and operated Buchanan Lumber.
He was also one of more than thirty investors who fought to keep the Oiler’s in Edmonton, buying the team from Peter Pocklington in 1998.
He was named Alberta Business Man of the Year in 2002 and was also a member of the Alberta Order of Excellence

http://www.cbc.ca/news/canada/edmonton/gordon-buchanan-businessman-and-parkinson-s-advocate-dead-at-85-1.2809776

New Israeli Technology Helps Treat Parkinson's Disease

New research dealing with monitoring and treatment of Parkinson's Disease will be presented at a conference at Samaria' Ariel University.


First Publish: 10/23/2014, 12:54 PM By Nancy Blank

Israeli-developed device will help monitor the develpment of Parkinson's Disease

New research dealing with the monitoring and treatment of patients with Parkinson's disease using wearable technology and advanced data analysis will be presented at a conference Thursday at Ariel University in Samaria (Shomron) by Dr. Shahar Cohen from Intel.
Intel's applied research for this project was done in collaboration with the Michael J. Fox Foundation for Parkinson’s Research, the largest private funder of Parkinson's research in the world.
The wearable technological device is something like a watch that patients wear on their wrist. This device allows for symptoms to be continuously monitored and recorded, making up to 300 observations per second on every patient, thereby providing a more accurate picture of the effects of the disease.
With the new technology, this device can record such things as pulse, slowness of movement, tremors and sleep quality.
Constant monitoring also alleviates the burden of both doctors and patients, since until now data could only be collected for brief periods during visits to doctor's offices. 
According to developers, one of the key advantages, in addition to the large amounts of data that can be recorded, is that the information is totally objective. Doctors previously were forced to rely on their patients reports which makes for very subjective data, and can cause strain in the doctor/patient relationship. 
There are also huge variances in the way people suffer Parkinson's disease. The fact that the symptoms vary so greatly made it difficult for doctors to monitor alone. 
Researchers and developers hope that access to new and large amounts of data will significantly aid research and care for patients with Parkinson’s disease - with the objective of soon identifying a cure. 
“This will allow researchers to better understand how Parkinson's disease works and what the exact symptoms are,” Dr. Cohen explained. “Until now many aspects of the disease where virtually unknown because of the need for in depth monitoring of patients, now researchers will be able to get a much clearer picture of how the disease is affecting patients.” Dr. Cohen said.
Clinical trials have been carried out in both Israel and the United States. A large amount of data has been collected and further experiments are planned soon. 
For more information about the new technology and statements from patients and researchers: 
The conference was organized by Dr. Inon Zuckerman, Department of Industrial Engineering and Management, Ariel University. Artificial intelligence experts and researchers from around the world will come together to witness the presentation of the breakthrough research

http://www.israelnationalnews.com/News/News.aspx/186505#.VEmkj75tOS2

Wednesday, October 22, 2014

Levodopa dose linked to malnutrition risk in Parkinson’s disease



 Published on October 22, 2014 at 5:15 PM 

By Eleanor McDermid, Senior medwireNews Reporter

The malnutrition often seen in patients with Parkinson’s disease (PD) could be partly an effect of levodopa medication, research suggests.
Alice Laudisio (Campus Bio-Medico University, Rome, Italy) and colleagues found that the presence of malnutrition risk in patients with PD, based on a Mini Nutritional Assessment (MNA) score of 23.5 or lower, was significantly associated with the levodopa equivalent daily dose (LEDD).
However, it was not related to dose of dopamine agonists, they report in Movement Disorders.

Of the 75 patients in the study, 35% were at risk of malnutrition. These patients were taking an average LEDD of 11.3 mg/kg, compared with 8.4 mg/kg among those not at risk. They also had lower levels of total serum proteins and higher Unified Parkinson's Disease Rating Scale scores (UPDRS; 57 vs 43).
The researchers suggest that the association between malnutrition and the LEDD might be an effect of dyskinesia caused by levodopa medication, or the need to take the drug several times daily in fasting conditions. Or malnutrition could result from a direct effect of levodopa on fat metabolism, skeletal muscle glucose uptake or eating behaviour, they speculate.

“Alternatively, patients taking higher [levodopa] dosages may have more advanced disease, possibly because of longer survival, thus having poorer nutritional status”, they say, although they note that the association remained significant after accounting for comorbidities.

A higher LEDD remained significantly associated with malnutrition risk after accounting for variables including age, gender and diagnosis of chronic pulmonary disease, as did a higher UPDRS score.
Conversely, malnutrition was not associated with dose of dopamine agonists, which have in fact been linked to weight gain and even compulsive eating.
“Further dedicated studies should assess whether use of dopamine agonists might prevent malnutrition, or at least improve nutritional status, in patients with Parkinson's disease”, conclude the researchers.


Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

http://www.news-medical.net/news/20141022/Levodopa-dose-linked-to-malnutrition-risk-in-Parkinsone28099s-disease.aspx

Design of micro and nanoparticles to improve treatments for Alzheimer's and Parkinson's


At the Faculty of Pharmacy of the UPV/EHU-University of the Basque Country encapsulation techniques are being developed to deliver correctly and effectively certain drugs
Enara Herran, a researcher at the UPV/EHU's Department of Pharmacy and Pharmaceutical Technology, is working to improve the way Alzheimer's and Parkinson's treatments are administered. And it is a fact that, as Herran herself stressed, "both diseases are becoming more and more common in our society". Both disorders affect the neurones: their structure and function is lost, and this in turn leads to the deterioration in the patient's motor, cognitive, sensory and emotional functions. As Herran pointed out, in many cases the drugs used to treat both Alzheimer's and Parkinson's only mitigate the symptoms; they do not act on the origin of the disease. "The treatment is usually on the basis of tablets taken by mouth."
But drugs of this type are not the only ones used to tackle both Alzheimer's and Parkinson's. Some drugs prevent neuron loss and help new ones to form; growth factors, for example. "In any case, they are not used so much because there is no effective, safe way of delivering them," said Herran. As the researcher explained, the drugs have to pass through the blood-brain barrier to reach the neurons, and that is no straightforward task. This is in fact the problem Herran is seeking to overcome by means of her research.
"Growth factors are encapsulated so that they can be administered more effectively and more safely. In other words, they are inserted into micro and nanocapsules and implanted in the brain by means of craniotomy. That way, the drugs would be released right where they have to act, and what is more, in an ongoing way and in the correct dose," explained Herran.
The micro and nanoparticles release these growth factors within a period ranging from 2-3 months and one year until the polymer has degraded. That way the patient does not have to take the medication every day. In any case, this is not the only advantage. In experiments carried out on rats and mice the encapsulated drugs have been found to be much more effective than those taken by mouth. As Herran pointed out, "these two diseases are already a problem for public health, and the scientific community is making a great effort in the quest for and in advances in new treatments".
Heading in the right direction
As Herran explained, in experiments conducted on animals they have tested two factors - the vascular endothelial growth factor (VEGF) and the glial cell-line derived neurotrophic factor (GDNF) - encapsulated in a biocompatible, biodegradable polymer - poly (lactic co-glycolic acid) (PLGA). "We obtained micro and nanoparticles using various encapsulation techniques. Initially, we did the tests for Parkinson's; first in cell cultures and then on mice. We got good results in both trials." Herran stressed that the mice treated with particles improved considerably: "A great improvement was noted in comparison with the control group in terms of behaviour as well as the healing of the damaged zones."
After that, they carried out the test for Alzheimer's in mice. Herran said that in this case they also achieved good results: "Three months after having carried out the procedure, the mice treated had good memories; similar to those of healthy mice. Through a histological analysis we found that the beta-amyloid plaques that develop in Alzheimer's had diminished considerably and so had the inflammation, and that angiogenesis had intensified."
The results and conclusions of these experiments have been publicised in specialised publications including the renowned Journal of Controlled Release. And this is in fact the subject of her PhD thesis. Although the research has not been completed, Herran said she is now doing research into the way of obtaining "better formulations", so as not to have to implant the micro and nanoparticles in the brain. The final goal is clear: to develop the most effective, safest and most suitable way of treating Parkinson's and Alzheimer's.
http://www.medicalnewstoday.com/releases/284196.php

Newcastle study shows link between walk and dementia in Parkinson's disease sufferers Oct 21, 2014 22:01 By Helen Rae


Newcastle University medical school



Experts in Tyneside have found a definitive link between the way someone walks and dementia linked to Parkinson’s disease.
The findings by researchers at Newcastle University mean that gait may be used as an early warning sign to help predict the development of cognitive impairment and dementia in the neurological disorder.
It has been known for several years that there is a link between walk disturbance and dementia in older adults, however until now the relationship has not been clear in Parkinson disease sufferers.
Lynn Rochester, professor of human movement science at Newcastle University and lead author of the paper, said: “The relationship between gait and cognition has never been established this early on and in such a large group of Parkinson’s before.
“In the future walking patterns may be a useful early warning system to help identify dementia risk in Parkinson’s.
“Subtle changes in someone’s walking pattern, for example slowing down of steps, and increased sway from side to side are related to cognitive function even before changes are seen in cognitive tests.
“Ongoing work will confirm if it is possible to predict future cognitive decline and dementia risk. However, this early work shows great promise.
“If we can use this and test people who may be at risk, then we could pick up the early signs and begin treatment and advice.”
If subtle changes in walking patterns, some of which are undetectable to the eye, could be an early warning sign of cognitive decline then it could be a guide to alert medical practitioners that treatment is required. Although there is no cure, early treatment can help to manage symptoms.


Dr Beckie Port, Parkinson’s UK research communications officer, said: “We know that people with Parkinson’s are at greater risk of developing problems with dementia than people without, however we still don’t fully understand the relationship between the two conditions.
“This research, which builds upon our £1m study into Parkinson’s related dementia, provides crucial insights into subtle changes in walking that could help us identify people with Parkinson’s who are at risk of developing dementia and problems with thinking and memory at a much earlier stage.
“This means people at risk can be monitored closely, and receive treatments at an earlier stage.”
More than 120 people with Parkinson’s disease were tested, making Newcastle University’s study the biggest in early Parkinson’s disease and they were compared to over 180 older adults.
Volunteers were asked to walk for two minutes in the lab and their stride pattern was then analysed.

Factors such as the length of stride, and sideways sway were looked at in a specially designed gait laboratory at the Clinical Ageing Research Unit, a clinical research facility jointly managed by Newcastle University and the Newcastle Hospitals Foundation Trust.
http://www.chroniclelive.co.uk/news/health/newcastle-study-shows-link-between-7973701

Tuesday, October 21, 2014

Protecting connections in brain could halt Parkinson's



Stopping the death of synapses - the connections between nerve cells in the brain - could provide a new way to tackle Parkinson's, which affects one in 500 people in the UK (1).
A study, published in Nature Communications (2), reveals the death of synapses in the brain may be due to proteins called Wnt not working properly.
The researchers gave mice drugs to stop Wnt proteins working and saw problems with movement, one of the main symptoms of Parkinson's. 
The study, carried out at University College London (UCL) with funding from Parkinson's UK, suggests that restoring Wnt's protective abilities in people with Parkinson's could stop synapses dying, and the condition progressing.
Parkinson's affects over 127,000 people in the UK, and 7.5 million worldwide (3).There are currently no drugs which can stop Parkinson's progressing. Levodopa (4) - the most common drug used to manage the symptoms of Parkinson's - is over fifty years old, and can have side effects like uncontrolled movement and impulsive behaviours.
Parkinson's UK researcher Dr Soledad Galli, who led the study at UCL, said:
"Looking at synapses is a very new area in Parkinson's research. We now need to see if what we've found in mice holds true when we study samples from people with Parkinson's.
"If we confirm that Wnt is involved in the early stages of Parkinson's this throws up exciting possibilities, not just for new treatment targets, but also for new ways to identify people with Parkinson's early on in their condition."
Dr Beckie Port, Research Communications Officer at Parkinson's UK, which helped to fund the study, said:
"We urgently need drugs that can stop Parkinson's getting worse, rather than just masking the symptoms. Until now most of the research to find these drugs has focused on preventing the death of nerve cells.
"This research - which instead looks at how to protect the bridges between nerve cells - could open up completely new routes towards our goal of a cure for Parkinson's."

Monday, October 20, 2014

Parkinson's Drugs Can Be A Gateway To Sin

Some Parkinson's drugs can trigger gambling problems that lead to bankruptcy.
Drugs that are commonly prescribed to help people cope with Parkinson's 
disease have been linked to bizarre changes in behavior that patients and 
doctors should be on guard against, researchers say.
The disturbing side effects include compulsive gambling, uncontrollable shopping and a sudden obsession with sex.
The problems with the drugs, called dopamine agonists, are serious enough that the researchers say the Food and Drug Administration should require the medicines to carry what's called a black-box warning, one of the most prominent and serious cautions used for prescriptions drugs.
Some of the drugs are also prescribed for restless leg syndrome and hyperprolactinemia, a hormonal condition that can trigger milk production.
While the problems with the dopamine agonists have been noted in the past, 
the recommendation for a more prominent warning comes come after researchers sifted through 2.7 million reports of drug reactions submitted 
to an FDA database between 2003 and 2012.
The researchers from the Institute for Safe Medicine Practices, Harvard and the University of Ottawa found 1,580 adverse drug events involving impulse control disorders. A little less than half, or 710 reports, were associated with dopamine receptor agonist drugs.
The link was strongest for pramipexole, brand name Mirapex, and ropinirole, brand name Requip. The instructions for doctors who are thinking about prescribing Mirapex already carry a warning that says patients taking the medicine "may experience compulsive behaviors and other intense urges." Requip, a treatment for restless
The results were published online Monday by JAMA Internal Medicine.
Back in 2005, doctors from the Mayo Clinic reported 11 cases of patients who became compulsive gamblers after taking dopamine agonists. A 52-year-old man lost $100,000 in casinos after previously gambling only once in his life. He also became fixated on pornography and obsessed with sex, carrying on extramarital affairs. A month after stopping the drug, he was his old self.
Doctors and patients may have overlooked the problems. In a commentary accompanying the latest findings, two Johns Hopkins doctors wrote that nausea, dizziness and other physical side effects are more typical parts of the conversations between doctors and patients about drugs. "During an office visit, a patient is unlikely to spontaneously mention, 'By the way, doctor I lost $250,000 in casinos last week' or 'I spend all night on Internet pornography sites and am soliciting prostitutes,' " they wrote.
Neurologist Howard Weiss, a co-author of the commentary, tells Shots that these drug-related compulsive behaviors haven't gotten the attention in the medical community that they deserve. A heightened warning in the drugs' instructions could help make the risk clearer, Weiss says. The behavioral problems, he says, "are more important than 99 percent of the other side effects that are being listed."
Weiss says he's had at least three patients who have lost their homes because of bankruptcy after taking the drugs.
When he asked an elderly patients taking one of the drugs if she ever gambled, she replied, "Gambling is the work of the devil." But it turned out she had been buying hundreds of dollars' worth of lottery tickets a week, a habit she didn't consider to be gambling.
Weiss says the behavioral problems usually go away after patients stop taking the medicines. He also says the drug combination carbidopa-levodopa, another Parkinson's treatment, works better and doesn't increase the risk for impulsive behavior.
http://www.npr.org/blogs/health/2014/10/20/357586341/parkinsons-drugs-can-be-a-gateway-to-sin?utm_campaign=storyshare&utm_source=facebook.com&utm_medium=social