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Saturday, January 30, 2016

Phone app to help spot Parkinson's disease symptoms

January 30, 2016

Analysing data collected on our mobile phones could give insights into our health.
Up to 10 million people around the world are living with Parkinson's disease, which causes symptoms such as a shuffling walk and tremor in the hands. 
But researchers in the UK hope that a phone app, which records a patient's movement and voice patterns, could help their doctor to monitor their progress more accurately. 
The app includes seven different tests - for tremor, walking gait, reaction times and voice. 
Dr Fahd Baig, clinical researcher at the Oxford Parkinson's Disease Centre, says that there are tell-tale signs in the voice of a Parkinson's patient. 
Results from one of his pilot studies indicate that simply getting a patient to say "ahhh" into a phone means the app can spot this with 99% sensitivity. 
Lorna Stewart reports.

To listen and watch video:
http://www.bbc.com/news/health-35434278 

http://health.einnews.com/article/309148642/DB8f9aMqsOSZJwDn

Friday, January 29, 2016

Connecting the Dots between Parkinson’s Protein

FoxFeed Blog 

 by  Maggie McGuire Kuhl, January 29, 2016

The cellular processes that keep us alive and healthy require thousands of microscopic players — proteins and enzymes and other workers on the line to tweak this, add that and keep us breathing and moving. Medical researchers try to name those workers and plot that line so that when something goes wrong, they know who may be involved and where they can intervene to fix the process.
Today a group of researchers led and funded by The Michael J. Fox Foundation (MJFF) have connected the dots between one of the most well-known workers in Parkinson’s disease (PD), the LRRK2 protein, and another set of proteins called Rabs.
Investigators from MJFF, the Max Planck Institute of Biochemistry in Germany, the University of Dundee in the United Kingdom, GlaxoSmithKline and Merck & Co., Inc. published a paper today detailing that connection in the online, open-source journal eLife. The team discovered that LRRK2 regulates cellular trafficking (moving cellular parts around and into/out of the cell) by deactivating certain Rab proteins.
“Identification of Rab proteins as a LRRK2 substrate presents a tool to measure the impact of drugs in testing. This critical component will advance development of these therapies to slow or stop Parkinson’s disease, patients’ greatest unmet need,” said Marco Baptista, PhD, MJFF senior associate director of Research Programs.
Mutations in the LRRK2 gene are the greatest known genetic contributor to Parkinson’s disease, accounting for one to two percent of all cases of PD and more in certain groups such as those of Ashkenazi-Jewish decent. Pharmaceutical companies are developing drugs against LRRK2 to correct the effects of those mutations and treat PD. While especially promising for people with a LRRK2 mutation, there is potential that such a treatment would help people without that genetic link, as well.
This connection of LRRK2 to Rabs is an important step for Parkinson’s drug development for three reasons:
It tells us more about LRRK2 biology and opens new roads to research. With this dot connected, we can look for other players that may be impacted by Parkinson’s dysfunction.
It gives us another thing to measure. LRRK2 has a low activity level, so measuring its action and the impact of drugs has been difficult. Rabs can act as a secondary measure to see if a drug against LRRK2 ishaving an effect on correcting the cellular process.
It points us to a potential new drug target. If LRRK2 dysfunction then leads to Rab dysfunction, we may be able to target Rabs to correct that problem and stop Parkinson’s disease.
“The pathological cascade leading to brain diseases such as Parkinson’s likely includes many cellular players,” said Matthias Mann, PhD, director of the Department of Proteomics and Signal Transduction at the Max Planck Institute of Biochemistry. “The identification of this LRRK2 substrate gives us a central piece in this puzzle and another potential place to intervene in the disease process.”
One of the key roles of our Foundation in the Parkinson’s research field is to unite all-star teams like this to problem solve around priority drug targets such as LRRK2. The consortium used a combination of tools developed by the partners — pre-clinical models from MJFF and GlaxoSmithKline (GSK) and drug candidates from GSK and Merck — and expertise in state-of-the-art technologies such as mass spectrometry, an analytic chemistry technique.  These tools, and the collaborative spirit that united the partners, were necessary to make this finding.
“This unique model of collaboration and our systematic approach across laboratories using advanced technologies and layers of confirmation provide a firm foundation from which to continue this line of investigation and further refine our understanding of the LRRK2 Rab relationship,” said Dario Alessi, PhD, director of the Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee.
With additional MJFF funding, this group now is working to further characterize the Rab proteins modified by LRRK2 and to understand how an imbalance in cellular trafficking leads to the degeneration of neurons seen in Parkinson’s disease.
https://www.michaeljfox.org/foundation/news-detail.php?connecting-the-dots-between-parkinson-proteins

PDMDS Finds a Way to Tackle Parkinson’s Disease

By Express News Service

Published: 30th January 2016 

HYDERABAD: Most of us begin walking at the age of one. While it seems like a struggle initially, overtime walking becomes involuntary and effortless. Similarly, balance, fine motor skills like writing, drawing also evolve with age and eventually become involuntary. All these actions and more can be collectively called ‘movement’. While some of us experience some difficulties with walking and balance in our late 60s, people with Parkinson’s disease suffer from significant movement difficulties that depreciate their quality of life drastically as the disease progresses.
Parkinson’s disease is a movement disorder presenting with motor symptoms such as:
  • Tremors
  • Rigidity
  • Slowness of movement
  • Postural instability
However, almost all patients with Parkinson’s also suffer from non-motor symptoms like:
  • Speech and swallowing difficulties,
  • Depression and anxiety,
  • Constipation and urinary troubles,
  • Sleep anomalies,
  • Hallucinations and delusions,
  • Cognitive problems like memory, attention and visuo-spatial reasoning.

It is because of a combination of these symptoms, that everyday become a challenge for people with Parkinson’s.
In fact, the realities of a person diagnosed with Parkinson’s go beyond the visible symptoms and the financial strain that this disorder brings due to its irreversible and progressive nature. These
patients, like any of us, have lived their whole life independently, having handled all their responsibilities almost single-handedly. A diagnosis of Parkinson’s, then makes them people who are surviving within themselves struggling with denial, loss of independence, fear of social stigma and embarrassment, social isolation, feelings of self - directed anger, changing personal and family dynamics and a lot more. The saddest truth is that several of them do not move beyond this stage.
The Founder of the Parkinson’s Disease Movement Disorder Society (PDMDS) and neurologist DrBS Singhal wanted to have a common platform for those afflicted by this condition - for them to be able to congregate, share, educate, motivate, inspire and become empowered. Thus, the Parkinson’s Disease and Movement Disorder Society was founded, an all India Charitable Society established in 2001 under the Societies Registration Act of 1860. PDMDS has centres across India, like Maharashtra, Goa, Gujarat, Telangana, Karnataka, and West Bengal.
This eases the accessibility to people with Parkinson’s, provides rehabilitation based on the multidisciplinary model of care which draws from the fields of neurology, physiotherapy, occupational therapy, speech therapy, psychology and cognition, diet and nutrition, and alternate therapies such as music, dance and arts. These therapies are systematically used as adjuncts to medical therapy for Parkinson’s worldwide but are not used as much in India.
The society’s centre in Telangana is located at NIMS Hospital, Panjagutta, in Hyderabad. We conduct our sessions in the Department of Neurology with the support of Dr Rupam Borgohain and Dr Rukmini Mridula. This centre was started two years ago with the objective of spreading awareness, providing specialized, holistic care to each patient with Parkinson’s disease in Telangana. Over these two years, we have seen nearly 200 patients in this centre, some of whom even come from places like Warangal and Guntur just to attend our sessions. Many aspects like occupational
therapy, nutrition for Parkinson’s, education about psychological and sleep symptoms, were unknown to patients and they found it enriching to know about them. We provide them with handouts that they can take home, so that what is learnt in the session is adapted into their daily lives. We also assess patients on how much they have improved overtime as a result of these
therapies, so that we have a scientific way of identifying our services and their efficacy. Parkinson’s is a progressive condition and eventually, many patients become home-bound. For these patients, we provide free home visits to guide them about changes that can still be made. Our other welfare activities at PDMDS, Hyderabad include, providing free medications for the needy, assistive devices like wheelchairs and disability certificates for those who need it. We also conduct awareness sessions at old age homes, senior citizens groups, medical groups to create awareness about
  • The uniqueness of our approach is that our services are specially designed only for Parkinson’s and other movement disorders, which provides patients with therapies that are scientific, innovative and in depth.
  • Another direct benefit is that our services are free of cost, which makes it accessible for patients from all strata of society.
  • What is most enlightening in our journey with patients at PDMDS, however, is that they now know that they are not alone. The feelings of isolation, anxiety and even guilt go away as soon as they realize there are several others suffering like them. In our sessions, patients meet others with Parkinson’s and their families, share, interact and feel emotionally motivated to bring new changes into their lives. Our vision for the state of Telangana, is to make sure we reach out to every single person with Parkinson’s and provide them with innovative and culture-specific methods of care and rehabilitation.
Meghana Pradeep Co-coordinator & psychologist at PDMDS
http://www.newindianexpress.com/cities/hyderabad/PDMDS-Finds-a-Way-to-Tackle-Parkinson’s-Disease/2016/01/30/article3251645.ece?

Amarantus issues Chinese patent covering use of MANF for the treatment of Parkinson's

The patent issuance will provide intellectual property protection in China for protein therapy, gene therapy and cell therapy applications of MANF.
Amarantus develops treatments and diagnostics for diseases in the areas of regenerative medicine neurology, and orphan diseases.

Amarantus BioScience Holdings (OTCMKTS:AMBS), a biotechnology company, issued a Chinese patent entitled "Neurodegenerative Disorders" covering the use of MANF for the treatment of Parkinson's disease.
The claims issued extend patent coverage for MANF protein therapy, gene therapy and cell therapy applications into 2029, the San Francisco, California-based company said in a statement on Thursday.
"The Chinese market represents a potential significant market opportunity for Amarantus," CEO Gerald Commissiong said in the statement.
The company said on Friday that it will look to partner the development of MANF with a group in China capable of bringing that technology to market in that region.
This patent adds to Amarantus' international intellectual property portfolio covering compositions of matter, methods of use and formulations for MANF.
Shares fell 8.6% to $0.323 at 12:21 p.m. in New York, reversing an earlier gain
http://www.proactiveinvestors.com/companies/news/121962/amarantus-issues-chinese-patent-covering-use-of-manf-for-the-treatment-of-parkinson-s-121962.html?

GPi vs STN deep brain stimulation for Parkinson disease

January 27, 2016 

Three-year follow-up

  1. For the NSTAPS study group

ABSTRACT

Objective: To compare motor symptoms, cognition, mood, and behavior 3 years after deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) in advanced Parkinson disease (PD).
Methods: Patients with PD eligible for DBS were randomized to bilateral GPi DBS and bilateral STN DBS (1:1). The primary outcome measures were (1) improvement in motor symptoms in off-drug phase measured with the Unified Parkinson Disease Rating Scale (UPDRS) and (2) a composite score for cognitive, mood, and behavioral effects, and inability to complete follow-up at 36 months after surgery.
Results: Of the 128 patients enrolled, 90 were able to complete the 3-year follow-up. We found significantly more improvement of motor symptoms after STN DBS (median [interquartile range (IQR)] at 3 years, GPi 33 [23–41], STN 28 [20–36], p = 0.04). No between-group differences were observed on the composite score (GPi 83%, STN 86%). Secondary outcomes showed larger improvement in off-drug functioning in the AMC Linear Disability Scale score after STN DBS (mean ± SD, GPi 65.2 ± 20.1, STN 72.6 ± 18.0, p = 0.05). Medication was reduced more after STN DBS (median levodopa equivalent dose [IQR] at 3 years, GPi 1,060 [657–1,860], STN 605 [411–875], p < 0.001). No differences in adverse effects were recorded, apart from more reoperations to a different target after GPi DBS (GPi n = 8, STN n = 1).
Conclusions: Off-drug phase motor symptoms and functioning improve more after STN DBS than after GPi DBS. No between-group differences were observed on a composite score for cognition, mood, and behavior, and the inability to participate in follow-up.
Classification of evidence: This study provides Class II evidence that STN DBS provides more off-phase motor improvement than GPi DBS, but with a similar risk for cognitive, mood, and behavioral complications.
http://www.neurology.org/content/early/2016/01/27/WNL.0000000000002401.short?rss=1

Study could open door for new treatment targets to help Parkinson's disease patients walk more easily


Published on January 29, 2016 ·

Two secrets of one of the brain's most enigmatic regions have finally been revealed. In a pair of new studies, scientists from the Gladstone Institutes have discovered a specific neural circuit that controls walking, and they found that input to this circuit is disrupted in Parkinson's disease.
Walking becomes a major challenge for people afflicted by Parkinson's disease. Parkinson's is caused by a depletion of dopamine--an important neurochemical--in the basal ganglia (BG), a brain region involved in fundamental behaviors like movement, learning, reward, and motivation. In Parkinson's, an imbalance arises between two pathways in the BG: the direct or "go" pathway and the indirect or "stop" pathway. Ordinarily, these pathways work together seamlessly to control locomotion, but in Parkinson's the stop pathway overpowers the go pathway, making it difficult to initiate movement. How the imbalance between these two pathways developed remained a mystery--until now.


Correcting an Imbalance in the Brain
Published in Neuron, scientists led by Gladstone associate investigator Anatol Kreitzer, PhD, discovered that dopamine depletion causes a miscommunication between the BG and another region called the thalamus, an area thought to relay sensory information to the brain. This miscommunication results in a loss of input to the go pathway from the thalamus, which consequently disrupts movement. Blocking the connection between the two regions reversed the imbalance between the stop and go pathways and restored normal behavior in a mouse model of Parkinson's.
"This study provides strong evidence for a mechanism by which the stop pathway overcomes the go pathway in Parkinson's disease," says first author Philip Parker, PhD, a former graduate student in Dr. Kreitzer's lab at the Gladstone Institutes and the University of California, San Francisco (UCSF). "Our findings implicate the thalamus in the development of the disease, an area of the brain that has received relatively little attention in Parkinson's research."
"Several studies have targeted the thalamus with deep brain stimulation to treat Parkinson's, but the region's role in the disease was not well established," adds Dr. Kreitzer, who is also an associate professor of physiology and neurology at UCSF. "Our findings finally provide a clear picture of how the thalamus can imbalance neural circuits and suppress movement in this condition."



Discovering How the Brain Controls Walking
In the second study, published in Cell, the scientists discovered that the go and stop pathways from the BG control locomotion by regulating a group of nerve cells in the brainstem that connects the brain to the spinal cord. The researchers revealed that the go pathway selectively activates a type of neuron in the brainstem that releases the neurochemical glutamate, and these neurons are responsible for triggering locomotion.
The scientists used optogenetics--an innovative research tool that uses light to activate or inhibit select cells in the brain--to stimulate either the go or the stop pathway in mice that were running on a tiny treadmill, while recording neural activity in the brainstem. They discovered that the go pathway selectively activated glutamate neurons, causing the mice to move, whereas the stop pathway inhibited these neurons and made the mice stop.
"This is the first time we have been able to demonstrate how the go and stop pathways regulate locomotion," says Tom Roseberry, a graduate student in the lab of Dr. Kreitzer. "We show a very precise connection from the basal ganglia to the brainstem that controls movement."
Remarkably, the researchers discovered that the brainstem neurons can overpower the signals from the BG--that is, if glutamate neurons were turned on, the animal moved even if the stop pathway is activated.
"In order to understand why walking is particularly disrupted in Parkinson's disease, we need to map out the circuitry that controls locomotion," says Dr. Kreitzer. "Our study shows that a specific set of neurons in the brainstem are both necessary and sufficient to initiate locomotion. This finding could open the door for new treatment targets to help Parkinson's patients walk more easily."
Source:
Gladstone Institutes

Dance beneficial for Parkinson's disease, other movement disorders



January 29, 2016 
Carol Boutcher and Bruce Popielarski participate in a "Dance For Parkinson's disease" class recently at the YMCA in Ormond Beach. Dr. Mandeep Garewal, a neurologist in Ormond Beach, said the many steps involved in dance is what makes it beneficial for those with Parkinson's disease . “Dancing involves more complex moves then simply walking which activates more neurons and may translate into a higher yield exercise for preserving neuronal integrity — if done routinely,” Garewal said. News-Journal/David Tucker
At Dance for Parkinson’s disease, the music can be pop and high energy or it can be as alluring and sexy as Latin ballroom, but oftentimes it's peppy and nostalgic as an upbeat dance to the '50s classic, "Mr. Sandman."
Music for people living with a movement disorder needs to be stimulating, but it’s not simply the muscles that are getting a workout.
Imagination and memory come into play as well. Dancers must act out an imaginary activity — such as hitting a golf ball or blowing up a balloon — before they can leave the dance floor.
The evocative power of music has the ability "to alleviate a lot of symptoms,” including inhibition and social isolation, said Vince Kinsler, the executive director of the Parkinson’s Association of Greater Daytona Beach, which underwrites the cost of the four-times-a-week dance classes at four YMCA's in Volusia County.
There's power in community, too.
“When they are dancing, they’re with other people who don’t care what they look like," Kinsler said.
His organization has 630 members in Volusia and Flagler counties, but Kinsler believes many more locals are affected by Parkinson's because of the big turnout at monthly lectures given by neurologists and other specialists. Kinsler said he often he sees a "lot of faces" he has never seen before at these talks.
Kinsler used to think many people were "in the closet" with their Parkinson's, but many people might also be too busy to join an organization. They still might be at early stages of Parkinson's and are still working 9-to-5 jobs.
Because Parkinson's is so gradual, many people might have the disorder but don't know it yet, Kinsler said. It's common for people to live with it for years before they are diagnosed, he said.
Parkinson's is a progressive disorder of the nervous system with symptoms such as tremors, stiffness and slowing of movement, caused by the breakdown of neurons and the loss of dopamine.
There is no known cure but regular exercise is thought to be helpful in alleviating the symptoms.  The Mark Morris Dance Group of Brooklyn, New York, has taught instructors around the country on how to "Dance with PD," including the instructors at the local YMCA.
Dr. Mandeep Garewal, a neurologist in Ormond Beach, said the many steps involved in dance is what makes it beneficial.
“Dancing involves more complex moves then simply walking which activates more neurons and may translate into a higher yield exercise for preserving neuronal integrity — if done routinely,” Garewal said.
“Motor memory and balance can improve with dancing,” Garewal said.
The exercise needs to be habitual to be effective, Garewal added.
John Mirabella, a Port Orange man who has Parkinson's, said he notices a difference in his health if he stops dancing for a week to go on a trip. He usually dances three times a week at the Y.
“With Parkinson's, the more you move, the better off you are,” added John Gerback of Ormond Beach after a recent dance class.
“Otherwise you get to the point where you stiffen up, and that’s a big problem,” John said. His wife, Gloria, has lived with Parkinson’s for the past 15 years.
Patricia Mirabella, wife of John, said Parkinson's can impact the simple kinds of movement that most people take for granted. "Getting out of a car, getting out of a chair, just pivoting is a big deal for (with people with Parkinson's),” said Patricia.
 “Reaching for something in a cabinet could throw them off their balance," Patricia said.
Patricia likes that every dance class includes stretching and breathing exercises. "It doesn’t seem like much to you and I, but to them it’s a big deal," Patricia said.
After the dance class, there is social time with coffee and cookies.
“It’s good to be with other people who are in the same shoes as you,” Patricia said. “They can tell you what they found to be helpful, even give referrals to doctors.”
Kinsler appreciates the effort people put into the dance.
“I don’t have the disease. I am relatively healthy. I could benefit by moving and exercise, but I don’t take advantage of it to the degree that I should," Kinsler said.
“People with Parkinson's are already in a compromised state,” Kinsler said. “Because this disease is so miserable, they are a highly motivated group of people.”
http://health.einnews.com/article/309006748/kQ7qcAKddEMfxgGO

This scan can watch concussion recovery inside your brain

January 29, 2016 by Meg Graham, Chicago Tribune



An Israel-based health firm with Chicago ties is developing its non-invasive brain scan, used to evaluate concussions, to take on depression, Alzheimer's and Parkinson's disease.
lMindA, an Israel-based firm founded in 2006 by Amir Geva, builds a Brain Network Activation  that helps clinicians assess , in hopes of better diagnosing or treating neurological disorders.
The company has its U.S. headquarters in north suburban Glenview, Ill., with 12 employees and has received funding from private Chicago investors. Late last year, the company received a $28 million Series C funding round to perform clinical studies, develop its technology and take it to new clinics, ElMindA CEO Ronen Gadot said.
The firm has FDA clearance to test working memory, attention and sensory processing in individuals ages 14 to 24.
Its first U.S. customer, Oak Brook-based Athletico Physical Therapy, offers BNA tests in its Niles, Aurora, Bannockburn, Orland Park and LaGrange Park, Ill., locations. During a $199 test, customers are outfitted with a net of sensors, intended to indicate how brain stimulation - or "neuronal firings" - are behaving under the surface.
"We're measuring the electrical field on top of your skull and trying to analyze it with sophisticated tools and algorithms in order to infer what's going on inside the brain," Gadot said.
Patients wear the sensor net to measure brain activity as they hit a button during a reaction test, then the system uploads results into a web portal - where findings can be shared with the patient and medical professionals.
Michael Palm, manager of concussion services at Athletico, said the company markets the test to youth athletes. The company offers discounts on the test for teams or groups. ElMindA hopes screening tests will one day become a regular part of a patient's checkups, even before a concussion or emergence of another brain disorder.
"If I will be able to follow your brain and how it is working, I will be able to early detect signs of deterioration, signs of change - that could be very helpful for diagnostics and also making better treatment decisions," Gadot said.
Such a test might also have implications for disorders like Alzheimer's disease or depression, Gadot said. Earlier detection could allow pharmaceutical companies to test drugs on patients in earlier stages of disease.
"It has never proven to be very effective to treat a disease at its later stage," he said. "The earlier you start intervening, the better chances you have for success. But for that, you really need to have better tools to early detect those changes."
Stephanie Kolakowsky-Hayner,  of the New York-based Brain Trauma Foundation, said a number of new technologies to diagnose and treat brain injuries have emerged. But they require extensive research and testing before  injury experts endorse one over another.
"All of these things are really actively being researched," she said. "Nothing shoots out above anything else."
http://medicalxpress.com/news/2016-01-scan-concussion-recovery-brain.html

Gene Driving Human Evolution May Contribute to Parkinson’s Disease

Gene regulator GABPa controls master switch in gene regulation


BY MAGDALENA KEGEL



A study published in the journal Molecular Biology and Evolution shows that the global gene regulator GABPa is controlling uniquely human genes – and may contribute to diseases like Parkinson’s.
The team, led by Robert Querfurth, explored the gene regulator – known as a transcription factor in scientific language – to understand its role as a master switch in human gene regulation. They started by investigating which genes are under the influence of the transcription factor, observing that binding sites for the regulator were common in genes that are important for central nervous system functions unique to humans.

GABPa exerts its action by binding to a so-called tandem repeat; a sequence of four DNA bases that is conserved among all primates as well as in cats, dogs and cows. The team used ChIP-Seq – a technique for identifying genome-wide binding sites in the DNA-binding transcription factors. They found that GABPa had 11,619 binding sites spread across 4,000 genes in the different species.

By comparing the DNA of 34 mammals to humans, they found 224 GABPa binding sites unique to humans. They further explored the function of the regulator by comparing the effects of the transcription factor – as well as mutated forms resembling ancestral states of the regulator – in chimpanzee, macaque, and human cultured cells.
The team introduced a human version of a GABPa binding site into primate cells and saw that the transcription of the genes under control of the regulator was increased. This suggests that a mutation in the GABPa drove the evolution of uniquely human characteristics – and possibly also diseases. “Mutations that cause changes in the regulation of gene activities are one of the major factors in shaping species during evolution,” Querfurth said in a press release. “Our study demonstrates how, out of the millions of DNA regions in which we differ from other apes, we can sift out those that, in response to a specific regulatory protein, cause gene activity changes in human cells. In this set, we find genes involved in brain and breast development and also in diseases like Alzheimer’s and Parkinson’s.
http://parkinsonsnewstoday.com/2016/01/29/gabpa-a-driving-force-behind-human-evolution/

New therapy halts progression of Lou Gehrig's disease in mice