Researchers identify biological process that triggers Parkinson’s disease

PARKINSONS DISEASE

By Nicole Kwan

Published April 10, 2014

New research has identified a biological ‘trigger’ for Parkinson’s disease. The findings, published in the journal Cell, may lead the way to early diagnostic tools and treatments that could shut down the disease before symptoms progress in patients.

Using both human neurons and fruit flies, researchers at Johns Hopkins have identified a protein, s15, that triggers a common form of Parkinson’s disease. The protein is enabled by an enzyme - leucine-rich repeat kinase 2 (LRRK2) - which then causes neurodegeneration.

Previous research has shown that mutations in LRRK2 are linked with neurodegeneration, and therefore, the progression of Parkinson’s disease. LRRK2 had been previously identified to be a protein kinase, which means it is a type of enzyme that adds phosphates on to other proteins and either turns proteins on or off or changes the protein’s activity. However, the proteins LRRK2 was acting on were unknown—until now.

“How mutations in [LRRK2] cause Parkinson’s disease aren’t well known, and what this study does is provides a pretty convincing set of data on how mutations in LRRK2 cause Parkinson’s disease,” study author Dr. Ted Dawson, professor of neurology and director of the Johns Hopkins Institute for Cell Engineering, told FoxNews.com.

The study’s findings suggest that inhibiting s15 and LRRK2 could prevent the loss of dopamine neurons and the onset of Parkinson’s disease. LRRK2 inhibitors exist, but have not been tested in patient trials. Studies are needed to identify inhibitors of s15, Dawson said.

Parkinson’s disease is a neurodegenerative disorder that affects nearly one million people in the U.S., according to the Parkinson’s Disease Foundation (PDF). With the disease, the brain loses dopamine-producing cells— dopamine sends messages to the brain control movement and coordination.

Symptoms vary from person to person, and are progressive, meaning they continue to worsen over time. According to the PDF, they can include tremor of the hands, legs and face, slowness of movement, stiffness of the limbs, and impaired balance and coordination.

Currently, the drug levodopa is used to treat the symptoms of Parkinson’s. While effective, it doesn’t treat all the symptoms, has side effects and doesn’t prevent degeneration. Researchers hope their study of LRRK2 could lead to an earlier diagnosis and better treatments for Parkinson’s.

There is a genetic test for Parkinson’s, but it’s only being used for research purposes because there aren’t therapies for patients yet, Dawson said.

“The general idea now is that… the degenerative process is starting many, many years before people start to manifest with symptoms,” Dawson said. “Once we do have [medications] that slow the progression, there are people who have [mutations in LRRK2] who you’d think would want to know and would want to take it.”

Development of consumer-ready drugs could take years; Dawson estimated 3 to 5 years for LRRK2 trials with patients and another 10 years for s15 inhibitors.

“If you look at neurodegenerative diseases, they’re a major and substantial health problem for the U.S. and it’s only going to get worse, but the U.S. is not investing the required resources to really make substantial headway into treating not only Parkinson’s but other neurodegenerative disorders,” Dawson said.

Alpha-synculein: A Growing Host of Therapeutic Approaches

January 28,2014 MJFF

Bottom line takeaway: In 1997, researchers learned that the protein alpha-synuclein and the gene that encodes the protein play a role in Parkinson's disease. Since then, alpha-synuclein has been the focus of intensive efforts by researchers working to definitively characterize its role in PD and its potential as a target for neuroprotective therapies. The Michael J. Fox Foundation is helping to lead these efforts, and awardees are engaged in a range of promising projects to develop therapies against alpha-synuclein.

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The potential for patients: Alpha-synuclein is a protein whose function in the healthy brain is not currently known, but which is of great interest to Parkinson's researchers: Clumps of alpha-synuclein exist in the cells in all people with PD. Researchers hypothesize that preventing or clearing out these clumps may prevent, slow or halt disease progression. Since alpha-synuclein may play a role in the development of both genetic and idiopathic cases of Parkinson's, a therapy against this target could help all those living with PD.

The challenge for researchers: While they know what they want to do, researchers don’t yet know how to do it. How can they stop the alpha-synuclein from clumping? They’re trying a variety of approaches such as immunotherapy — using introduced or induced antibodies to attack the protein clumps — and drug compounds that may bind to alpha-synuclein or its related pathology (such as enzymes) and prevent toxicity.

The MJFF approach: The Foundation is supporting research in various stages of development. Pre-clinical studies are looking at antibodies and vaccine approaches. Some established drug compounds are in laboratory testing, and other projects are aimed at identifying compounds that can work against alpha-synuclein and related targets. The AFFiRiS Phase I clinical trial is testing a vaccine immunotherapy approach against alpha-synuclein, and results are expected in Q2 2014.

Reasons for optimism: Industry has taken interest in alpha-synuclein as a viable target. In 2013 biotech company Biogen Idec signed on to MJFF-funded projects from two smaller companies: Amicus Therapeutics is testing compounds to heighten GCase enzyme activity, which may keep alpha-synuclein in check, and Proteostasis is testing therapeutic candidates to inhibit the Usp14 enzyme, a strategy that has shown to prevent alpha-synuclein clumping in pre-clinical models. Biogen Idec’s support of these studies is a success of the MJFF de-risking model, which elevates promising early-stage research to the attention of larger funders and closer to the clinic.

MJFF research partners: The Foundation is supporting academic and industry partners around the world to speed research against this target toward clinical application for patients.

Notable quotes: “By affecting alpha-synuclein using antibodies, we may be able to slow the disease, preventing it from spreading to the nervous system. We are currently unable to offer treatment affecting disease progression, but treatment with antibodies may prove to have this potential,” says Kim Andersen, head of pharmaceutical company Lundbeck’s research in Denmark.

“We look forward to advancing our disease-modifying approach to develop therapeutic candidates that can address several protein aggregation disorders, including Parkinson’s and Alzheimer’s disease,” says Markus Haeberlein, MSc, PhD, senior vice president and head of research at Proteostasis Therapeutics.

Who’s to Blame? Finding Toxic Alpha-synuclein

Posted by  Maggie McGuire, April 24, 2014

Research has found more alpha-synuclein in the skin of PD patients (right) compared to controls. Image courtesy of Neurology.

Alpha-synuclein shoulders a lot of blame in Parkinson’s disease (PD). This protein clumps in the cells of all Parkinson’s patients, leading to cell dysfunction and cell death. But not all alpha-synuclein may be bad. Scientists do not yet know the normal function of alpha-synuclein, but it is likely that only certain species form the toxic aggregates seen in Parkinson’s.

Proteins occur in different shapes and structures thanks to splicing and modulations. When they interact with other compounds, proteins are changed slightly, resulting in different species of the same base protein.

A new funding program from The Michael J. Fox Foundation will support multi-institute teams to look for different species of alpha-synuclein in clinical samples and determine which play a role in the toxic PD clumps.

“Alpha-synuclein is our most promising target for a drug that could stop or prevent Parkinson’s,” said Todd Sherer, PhD, MJFF CEO. “Understanding what species of this protein are involved in the disease would accelerate development of a disease-modifying therapy.”

Researchers are already measuring alpha-synuclein levels in different parts of the body.

The Parkinson’s Progression Markers Initiative, the landmark biomarker study sponsored by MJFF, is looking at alpha-synuclein in cerebrospinal fluid. MJFF-funded researchers are investigating levels of this protein inthe salivary gland and the skin, among other regions.

Understanding which species of alpha-synuclein is toxic could lead researchers to develop more precise drugs that could prevent or break up the protein clumps. A more specified biomarker test of disease risk, onset or progression could allow for faster testing of those disease-modifying therapies, too.

The new funding program will support teams to look at alpha-synuclein in the central nervous system (brain tissue and spinal fluid) and in the peripheral nervous system (blood, plasma, other tissue).

Diagnosing Parkinson's From Voice Recordings And Smartphone Movements

Today it's expensive and difficult to test for the disease. One day, it could be as simple as a computer analyzing for telltale signatures in easy-to-access data.

About 6.3 million people suffer from Parkinson's disease worldwide, but it's a good bet that not all of those people have actually been diagnosed. There's no blood test for the disease, and the standard procedure today requires lengthy and expensive visits to a neurologist. In poor countries where there aren't many neurologists, there are probably thousands of sufferers who aren't officially counted, let alone treated.

The Parkinson's Voice Initiative aims to find a cheaper, more accessible method by categorizing people's voice patterns. Aside from trembling hands and stooped gaits, people with Parkinson's also exhibit telltale signs in their speech: a certain fluctuation and breathiness, for example. In time, the Parkinson's Voice Initiative hopes to develop a test that might involve nothing more than recording your voice--say, via an app or phone-in system.

The project is led by Max Little, a British mathematician and visiting professor at MIT. In 2012, Little announced he was looking for 10,000 volunteers to provide data for his work. And provide it they did. Six months later, 17,000 people--both sufferers and non-sufferers--had called special numbers to record their voice tracks. Now, Little is analyzing the recordings, looking for 300 markers at intervals of 8,000 times a second. Once finished, he'll create a system that analyzes voices automatically.

See his original TED talk is here:

"We're just trying to demonstrate that it's possible at the moment, but we would envisage something like a phone system where people could call in," he explains. "Then, it could be used as an indication of whether they need to go for a checkup or not."

Little has been analyzing voices since his PhD days, and only took a turn into Parkinson's research when a friend (a ballet dancer) got the disease. He then bumped into an Intel employee, who told him about Parkinson's projects the company had been working on (ex-CEO Andy Grove was diagnosed in 2000) and that voice patterns could be a viable research area. Little realized he could use his training in a new direction.

At the same time, Little has also been involved with work analyzing movement data from cell-phones. Last year, the Michael J Fox Foundation ran a competition to develop algorithms, so that doctors could monitor patients remotely (seeing, for example, how often they tremor).

Little hopes that crowdsourcing and machine learning could make collecting and analyzing data easier, and open up treatment options to more people.

"We live in a privileged world where the density of neurologists to patients is extremely high. But if you take areas of the world, you might be lucky that there's one neurologist in the entire population," he points out.

[Image: Abstract via Shutterstock]

Parkinson's takes a toll on families too [Commentary]

Parkinson's toll - baltimoresun.com

Parkinson's is a complex, chronic illness that we still know very little about; continued research, education and advocacy are crucial to getting closer to one day finding a cure.

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By Cory Booker

3:41 p.m. EDT, April 23, 2014

This year, approximately 60,000 Americans will be diagnosed with Parkinson's, joining the 1 million people already living with the disease in the United States and the 4 million to 6 million diagnosed with it worldwide. Their painful struggle is one that I know all too well.

I remember when my dad first had symptoms of Parkinson's, a motor system disorder that results from the loss of certain brain cells. For him, it started with a persistent numbness in his arm and hand that led to a decades-long battle with the ever-increasing symptoms that eventually took his life in 2013.

My father confronted challenges with an understanding that you can't always choose what life brings you, but you can always choose the attitude that you bring to life. It is this tremendous spirit and positivity that I remember most about him and try to emulate each day in his honor.

• While we had no family history or experience with Parkinson's, my parents found a strong support system that helped them through the various stages of the disease. In addition to family and friends, many local community members, neighbors and organizations opened their hearts and took time out of their busy schedules to advise, care for and be there for both my mom and dad. I feel blessed that my parents were surrounded by so many amazing people who offered guidance and understanding throughout their tough journey.

Since my brother and I did not live in the same town — or even the same state — as my parents, we were unable to offer the day-to-day physical support we wished we could. The task of primary caregiver was left to my mother. Not seeing my dad daily, my brother and I witnessed the disease advance in a more shocking and immediate manner that seemed worse with each visit, whereas my mom experienced it at a much more gradual pace.

As my father's disease progressed over time and even the simplest tasks became hard for him to tackle on his own, I grew increasingly concerned for my mom's health and well being.

Caregivers, like my mom, face extraordinary demands both physically and emotionally. More often than not, they are the ones navigating the treatment and care path — trying to figure out which approaches will bear the best results for their loved ones. As my father's needs for care grew — especially when Parkinson's began to affect his mental health — my mother eventually required home health care workers to help tend to my father's needs.

This is why I am so grateful for organizations like the National Parkinson Foundation (NPF) because I know that they, along with others, offer support, strength and hope to patients and caregivers. NPF's efforts to improve the quality of care for those with Parkinson's and educate all of us on this disease are truly important.

Education is crucial in early detection of Parkinson's symptoms and communicating immediate steps to take. Families are on the front lines of Parkinson's. Often it's the spouse, son or daughter who first notices something. Knowing what to look for and what to do can make a big difference. Resources such as those found at www.parkinson.org can provide life-saving information.

The Centers for Disease Control and Prevention rated complications from Parkinson's disease as the 14th leading cause of death in the U.S., with the prevalence expected to grow as the population ages. In our country, the economic burden of Parkinson's disease is estimated to be $14.4 billion annually.

Parkinson's disease does not discriminate; it affects all races, genders and social classes. Despite the growing body of research, Parkinson's is a complex, chronic illness that we still know very little about. Continued research, education and advocacy are crucial to getting closer to one day finding a cure.

Although Parkinson's eventually led to the end of my dad's life, I do believe that he and my mother showed triumphant strength against this relentless adversary. I am proud that as Parkinson's brought my dad greater and greater physical challenges, he evidenced greater and greater courage. I know there were days when the challenges were just overwhelming, but my parents never gave up, never stopped pushing forward; they never let the disease rob them of their dignity or love.

I am honored to continue that legacy and invite others to join me. April is Parkinson's Awareness Month — an important opportunity to learn more and get involved. As a nation, we can work together to meet the urgent challenge of Parkinson's disease and the burden of chronic illness in this country.

We must be, and can be, stronger in the face of it.

U.S. Sen. Cory Booker is a New Jersey Democrat. He can be reached at info@booker.senate.gov.

Read more: http://www.baltimoresun.com/news/opinion/editorial/bs-ed-parkinsons-disease-20140423,0,1494739.story#ixzz2zr9y4xD0

Let’s all work together to combat Parkinson’s

One million people in North America live with Parkinson’s disease, a progressive brain disorder for which there is no cure. Millions more are involved in caring for those who suffer from this complex disease affecting motor function, speech and cognition. And locally, thousands of people are afflicted with this disease.

April is Parkinson’s Awareness Month, and the National Parkinson Foundation Western New York Chapter encourages you to join our community as we take steps to promote greater awareness of Parkinson’s. There is much work to be done. The Centers for Disease Control and Prevention rated complications from Parkinson’s as the 14th leading cause of death in the United States. The prevalence of the disease is expected to increase substantially in the next 20 years due to the aging of the population and the age-related incidence of the disease. The nation’s economic burden of Parkinson’s is estimated at $6 billion annually.

At NPFWNY, our mission is to restore health, invigorate hope and improve the quality of life for patients living with Parkinson’s disease in Western New York while assisting their caregivers and families through education, awareness and advocacy. We believe every person diagnosed with Parkinson’s deserves the best care and treatment. Each month, support groups, programming and resources are provided for those living with Parkinson’s and their caregivers and we continue to look for ways to enhance those offerings.

We encourage the community to come together and show support for those touched by this debilitating disease. For more information, visit our website, www.npfwny.org. Together, we can make a difference in the lives of those with Parkinson’s disease and the ones who care for them.

A telemedicine case study tries virtual house calls in patients with Parkinson's disease

Virtual house calls are feasible and well-received among people with Parkinson’s disease, according to a telemedicine case study published today.

Dr. Ray Dorsey, a neurologist at University of Rochester Medical Center, led a project that offered free telemedicine visits to 50 Parkinson’s disease patients in California, Delaware, Florida, Maryland and New York — the states where he’s licensed to practice. Participating patients ranged from those who were getting a second or third opinion to others who were seeing a neurologist for the first time. They spent 30 to 60 minutes with a specialist using Vidyo’s web-based video conferencing software.

A summary of feedback from the project, as published in Neurology: Clinical Practice, reported that nearly all of the televisits resulted in some form of treatment recommendations, like changing or adding medications, discussing surgical options or recommending exercise. Four patients with unknown diagnosis were diagnosed with likely comorbidities, and four more were identified as potentially having impulse control disorders. Dorsey and his colleagues reported that patient satisfaction, as measured by a survey administered after the visit, exceeded 90 percent.

“We have an ample supply of neurologists in the country to take care of people with Parkinson’s, but because of distance, disability, and the distribution of doctors, many patients have a difficult time seeing a specialist,” he said in a statement.

The published study was supported by Verizon Foundation, medical device giant Medtronic and patient networking website PatientsLikeMe.Dorsey and colleagues at Johns Hopkins Medicine and University of Rochester Medical Center have been working for the past few years on demonstrating the benefits of telemedicine in Parkinson’s and plan to expand their most recent project. With additional support from the National Parkinson’s Foundation and the Patient Centered Outcomes Research Institute, they’re launching a new study called Connect.Parkinson. It will enroll 200 individuals beginning next year, some who will receive their usual care from a physician and others who will receive additional virtual care from a Parkinson’s disease center of excellence.

Despite the growing body of evidence around the benefits of telemedicine, a few big barriers remain. One is that, in some states, Medicaid and private insurance don’t reimburse healthcare providers for virtual consultations. The other is that physicians must be licensed to practice in the state that the patient is in.

Parkinson’s lends itself to telemedicine because so many aspects of the diagnosis and treatment involve conversation with an individual and observing him or her performing certain tasks. “James Parkinson wrote the seminal description of the condition in 1817 by watching people walk in the park,” Dorsey said. “This is just a 21st century application of that principal of observation.”

more: http://medcitynews.com/2013/12/case-study-telemedicine-tests-free-virtual-visits-parkinsons-disease-patients/#ixzz2zl16YX1A

Too much protein may kill brain cells as Parkinson's progresses

Date:

April 10, 2014

Source:

NIH/National Institute of Neurological Disorders and Stroke

Summary:

The most common genetic cause of Parkinson's disease destroys brain cells and devastates many patients worldwide, scientists have discovered. The investigators found that mutations in a gene called leucine-rich repeat kinase 2 may increase the rate at which LRRK2 tags ribosomal proteins, which are key components of protein-making machinery inside cells. This could cause the machinery to manufacture too many proteins, leading to cell death.

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NIH-funded scientists show that the deadly Parkinson's gene LRRK2 can kill nerve cells (green) by tagging the s15 ribosomal protein (purple), a cog in a cell's protein-making machinery.

Credit: Courtesy of Dawson lab, JHU Morris K. Udall Center of Excellence for Parkinson's Disease

[Click to enlarge image]

Scientists may have discovered how the most common genetic cause of Parkinson's disease destroys brain cells and devastates many patients worldwide. The study was partially funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS); the results may help scientists develop new therapies.

"This may be a major discovery for Parkinson's disease patients," said Ted Dawson, M.D., Ph.D., director of the Johns Hopkins University (JHU) Morris K. Udall Center of Excellence for Parkinson's Disease, Baltimore, MD. Dr. Dawson and his wife Valina Dawson, Ph.D., director of the JHU Stem Cell and Neurodegeneration Programs at the Institute for Cell Engineering, led the study published in Cell.

The investigators found that mutations in a gene called leucine-rich repeat kinase 2 (LRRK2; pronounced "lark two" or "lurk two") may increase the rate at which LRRK2 tags ribosomal proteins, which are key components of protein-making machinery inside cells. This could cause the machinery to manufacture too many proteins, leading to cell death.

"For nearly a decade, scientists have been trying to figure out how mutations in LRRK2 cause Parkinson's disease," said Margaret Sutherland, Ph.D., a program director at NINDS. "This study represents a clear link between LRRK2 and a pathogenic mechanism linked to Parkinson's disease."

Affecting more than half a million people in the United States, Parkinson's disease is a degenerative disorder that attacks nerve cells in many parts of the nervous system, most notably in a brain region called the substantia nigra, which releases dopamine, a chemical messenger important for movement. Initially, Parkinson's disease causes uncontrolled movements; including trembling of the hands, arms, or legs. As the disease gradually worsens, patients lose ability to walk, talk or complete simple tasks.

For the majority of cases of Parkinson's disease, a cause remains unknown. Mutations in the LRRK2 gene are a leading genetic cause. They have been implicated in as many as 10 percent of inherited forms of the disease and in about 4 percent of patients who have no family history. One study showed that the most common LRRK2 mutation, called G2019S, may be the cause of 30-40 percent of all Parkinson's cases in people of North African Arabic descent.

LRRK2 is a kinase enzyme, a type of protein found in cells that tags molecules with chemicals called phosphate groups. The process of phosphorylation helps regulate basic nerve cell function and health. Previous studies suggest that disease-causing mutations, like the G2019S mutation, increase the rate at which LRRK2 tags molecules. Identifying the molecules that LRRK2 tags provides clues as to how nerve cells may die during Parkinson's disease.

In this study, the researchers used LRRK2 as bait to fish out the proteins that it normally tags. Multiple experiments performed on human kidney cells suggested that LRRK2 tags ribosomal proteins. These proteins combine with other molecules, called ribonucleic acids, to form ribosomes, which are the cell's protein-making factories.

Further experiments suggested that disease-causing mutations in LRRK2 increase the rate at which it tags two ribosomal proteins, called s11 and s15. Moreover, brain tissue samples from patients with LRRK2 mutations had greater levels of phosphorylated s15 than seen in controls.

Next, the researchers investigated whether phosphorylation could be linked to cell death, by studying nerve cells derived from rats or from human embryonic stem cells. Genetically engineering the cells to have a LRRK2 mutant gene increased the amount of cell death and phosphorylated s15. In contrast, the researchers prevented cell death when they engineered the cells to also make a mutant s15 protein that could not be tagged by LRRK2.

"These results suggest that s15 ribosome protein may play a critical role in the development of Parkinson's disease," said Dr. Dawson.

How might phosphorylation of s15 kill nerve cells? To investigate this, Dr. Dawson and his colleagues performed experiments on fruit flies.

Previous studies on flies showed that genetically engineering dopamine-releasing nerve cells to overproduce the LRRK2 mutant protein induced nerve cell damage and movement disorders. Dr. Dawson's team found that the brains of these flies had increased levels of phosphorylated s15 and that engineering the flies so that s15 could not be tagged by LRRK2 prevented cell damage and restored normal movement.

Interestingly, the brains of the LRRK2 mutant flies also had abnormally high levels of all proteins, suggesting that increased s15 tagging caused ribosomes to make too much protein. Treating the flies with low doses of anisomycin, a drug that blocks protein production, prevented nerve cell damage and restored the flies' movement even though levels of s15 phosphorylation remained high.

"Our results support the idea that changes in the way cells make proteins might be a common cause of Parkinson's disease and possibly other neurodegenerative disorders," said Dr. Dawson.

Dr. Dawson and his colleagues think that blocking the phosphorylation of s15 ribosomal proteins could lead to future therapies as might other strategies which decrease bulk protein synthesis or increase the cells' ability to cope with increased protein metabolism. They also think that a means to measure s15 phosphorylation could also act as a biomarker of LRRK2 activity in treatment trials of LRRK2 inhibitors.

This work was supported by grants from the NINDS (NS038377, NS072187), the JPB Foundation, the Maryland Stem Cell Research Fund (2007-MSCRFI-0420-00, 2009-MSCRFII-0125-00, 2013-MSCRFII-0105-00), and the New York Stem Cell Foundation.

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Story Source:

The above story is based on materials provided by NIH/National Institute of Neurological Disorders and Stroke. Note: Materials may be edited for content and length.

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Journal Reference:

1. Ian Martin, Jungwoo Wren Kim, Byoung Dae Lee, Ho Chul Kang, Jin-Chong Xu, Hao Jia, Jeannette Stankowski, Min-Sik Kim, Jun Zhong, Manoj Kumar, Shaida A. Andrabi, Yulan Xiong, Dennis W. Dickson, Zbigniew K. Wszolek, Akhilesh Pandey, Ted M. Dawson, Valina L. Dawson. Ribosomal Protein s15 Phosphorylation Mediates LRRK2 Neurodegeneration in Parkinson’s Disease. Cell, 2014; 157 (2): 472 DOI: 10.1016/j.cell.2014.01.064

Dyskinesia and Dystonia

 

What is dyskinesia?

Dyskinesia is a difficulty or distortion in performing voluntary movements, which often occurs as a side effect of long-term therapy with levodopa. But it can also result from prolonged use of certain antipsychotics. Dyskinetic movements look like smooth tics — sometimes like an uncoordinated dance. People who experience dyskinesia sometimes mask the involuntary movement with finalistic movements (if the arm starts moving on its own, they might bring it to their head and adjust their hair, as if it was planned). Regretfully, we don’t yet have a specific therapy for dyskinesia. It normally improves with a reduction or redistribution of levodopa therapy, but this also is typically followed by an increase in rigidity or tremors, so it is hardly a solution.

What is dystonia?

A dystonia is an involuntary movement characterized by prolonged muscle contraction that can involve the entire body or an isolated area. Often dystonias are associated with pain (such as cramps). While dystonia can be a self-standing inherited (genetic) condition associated with medications or diseases other than Parkinson’s disease, it also can be caused by a lack of dopamine and therefore responds to dopaminergic therapy; this is typically the case in Parkinson’s patients. In Parkinson’s patients, dystonias can occur when medication wears off and dopamine levels drop under a specific threshold.

How can I control my dyskinesia?

Unfortunately, today there is no good solution to actively control dyskinesia. An important step is to actively adjust your medications for maximum medical benefit with minimal side effect; this is one of the reasons it’s so important to see a movement disorders specialist, who will have specific expertise in this area. Sometimes minimum adjustment in dosage and frequency can improve motor fluctuation, including dyskinesia.

Dyskinesia can worsen under stress (especially psychological stress), so reducing environmental stressors is important. Obviously, different people reduce stress in different ways. For some, it’s a yoga class, talk therapy, lighting an aromatherapy candle; for others it’s skydiving. What matters is figuring out what works for you, and then working plenty of it into your routine.

Dexterity and Parkinson's Disease

 

How can I minimize embarrassing dexterity problems?

Dexterity problems can include fumbling for bills, change, and credit cards at checkout counters. Staying at home is a great temptation when your symptoms are showing, but it only deprives you and your spouse or friends of the pleasure of each other's company. And it isolates you. The truth is that few people will even notice your symptoms. A bad tremor while making change is taken for a momentary rattling. Knocking over a glass at dinner? Spilled soup? It happens to everyone.

How can I minimize embarrassing dexterity problems such as fumbling for bills, change, and credit cards at checkout counters?

Some Parkinson’s patients embark on an endless search for the perfect wallet, but the issue is not limited to money. Car keys, theater programs, church bulletins, a glass of wine, or a plate of food at a buffet — worse yet, both a glass and a plate. Everyone drops things. It just happens more frequently with Parkinson’s patients, who carry around this baggage of "disease" that seems to get a little heavier with each mishap.

Compensatory strategies can be helpful: A large wallet for easy access, counting change ahead of time, not using change, asking a friend to hold your drink while you steady a plate, etc. When you encounter a new problem, think about the best way to handle it the next time. And remember, dropping change is a symptom of your disease, not a reflection on your character. The more you are out and about, the more people will see you, and visibility means greater acceptance from others as well as increased confidence. Parkinson’s disease doesn't have to be a prison.

Can Baker's Yeast Help Us Understand Parkinson's Disease?

FoxFeed Blog

Posted by  Nancy Ryerson, April 09, 2014

For years, researchers have used baker's yeast — the same ingredient that make bread rise — as a useful model for human diseases, including Parkinson's disease (PD). The yeast contains proteins similar to a PD-related protein called DJ-1, and new research into how yeast proteins function in a cell may help shine light on PD protein activity, according to findings published in the journal PNAS.

The protein DJ-1 has long been linked with Parkinson's disease, but researchers aren't sure what role the protein plays in the cell. In the study, scientists discovered that the yeast proteins that resemble DJ-1 are important for how cells break down and recycle damaged cell parts, in a process called autophagy.

"Lifespan and autophagy are central processes in the context of both Parkinson's disease and cancer,"Digital Journal reported on the study. "Based on this, the identified proteins provide researchers with a new model to explore."

The results may offer some insight into the role of DJ-1 in the cell, says Brian Fiske, MD, vice president of research programs here at the Foundation. But he cautions that much more research is needed.

"Researchers have long used yeast as lab models, and the jump from yeast to humans is often not a clear one," he says. "However, any new understanding of the players in Parkinson’s is progress toward better therapies.”

TAGS: Research News, Research Field News

Is Parkinson’s an Autoimmune Disease?

Attack by Own Immune System May Kill Neurons in Parkinson’s

Susan Conova / April 17, 2014

Posted in: Immunology, Neuroscience, Parkinson's Disease

Parkinson's Women Support via EPDA

2 hrs · 

YOU'RE KILLIN' ME-how about if the neurons in your brain are mistaken for foreign invaders and killed by your own immune system? The cause of neuronal death in Parkinson’s disease is still unknown, but a new study proposes that your brain might be falsely identifing the good and the bad!

Is Parkinson's an Autoimmune Disease? | Columbia University Medical Center

New findings that overturn a theory about the brain and the immune system suggest Parkinson's may be an autoimmune disease.

The cause of neuronal death in Parkinson’s disease is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders and killed by the person’s own immune system, similar to the way autoimmune diseases like type I diabetes, celiac disease, and multiple sclerosis attack the body’s cells. The study was published April 16, 2014, in Nature Communications.

“This is a new, and likely controversial, idea in Parkinson’s disease.”

“This is a new, and likely controversial, idea in Parkinson’s disease; but if true, it could lead to new ways to prevent neuronal death in Parkinson’s that resemble treatments for autoimmune diseases,” said the study’s senior author, David Sulzer, PhD, professor of neurobiology in the departments of psychiatry, neurology, and pharmacology at Columbia University College of Physicians & Surgeons.

The new hypothesis about Parkinson’s emerges from other findings in the study that overturn a deep-seated assumption about neurons and the immune system.

For decades, neurobiologists have thought that neurons are protected from attacks from the immune system, in part, because they do not display antigens on their cell surfaces. Most cells, if infected by virus or bacteria, will display bits of the microbe (antigens) on their outer surface. When the immune system recognizes the foreign antigens, T cells attack and kill the cells. Because scientists thought that neurons did not display antigens, they also thought that the neurons were exempt from T-cell attacks.

“That idea made sense because, except in rare circumstances, our brains cannot make new neurons to replenish ones killed by the immune system,” Dr. Sulzer says. “But, unexpectedly, we found that some types of neurons can display antigens.”

Four images of a neuron from a human brain show that neurons produce a protein (in red) that can direct an immune attack against the neuron (green). Image: Carolina Cebrian.

Cells display antigens with special proteins called MHCs. Using postmortem brain tissue donated to the Columbia Brain Bank by healthy donors, Dr. Sulzer and his postdoc Carolina Cebrián, PhD, first noticed—to their surprise—that MHC-1 proteins were present in two types of neurons. These two types of neurons—one of which is dopamine neurons in a brain region called the substantia nigra—degenerate during Parkinson’s disease.

To see if living neurons use MHC-1 to display antigens (and not for some other purpose), Drs. Sulzer and Cebrián conducted in vitro experiments with mouse neurons and human neurons created from embryonic stem cells. The studies showed that under certain circumstances—including conditions known to occur in Parkinson’s—the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in Parkinson’s were far more responsive than other neurons to signals that triggered antigen display.

The researchers then confirmed that T cells recognized and attacked neurons displaying specific antigens.

The results raise the possibility that Parkinson’s is partly an autoimmune disease, Dr. Sulzer says, but more research is needed to confirm the idea.

“Right now, we’ve showed that certain neurons display antigens and that T cells can recognize these antigens and kill neurons,” Dr. Sulzer says, “but we still need to determine whether this is actually happening in people. We need to show that there are certain T cells in Parkinson’s patients that can attack their neurons.”

If the immune system does kill neurons in Parkinson’s disease, Dr. Sulzer cautions that it is not the only thing going awry in the disease. “This idea may explain the final step,” he says. “We don’t know if preventing the death of neurons at this point will leave people with sick cells and no change in their symptoms, or not.”

The paper is titled: “MHC-1 expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration.” Other contributors are: from CUMC, Ellen Kanter, Jonathan Mandelbaum, Jean P. Vonsattel, and John D. Loike; from Sloan-Kettering Institute, Julius Steinbeck, Lorenz Studer, Sadna Budhu, and Luigi Zecca; from the National Research Council of Italy, Fabio Zucca and Pierluigi Mauri.

The authors declare no financial or other conflicts of interest. Columbia University and the La Jolla Institute for Allergy & Immunology have filed a patent application relating to T cell responses and Parkinson’s disease.

The research was supported by the NIH (R01NS064155 and U01NS082157), Caja Madrid Foundation; the JPB Foundation; the Parkinson’s Disease Foundation; the Udall Center of Excellence at Columbia; the University of Milan, the Italian Ministry of Education, University and Research; the Department of Defense; the Michael J. Fox Foundation; the M.E.M.O. Hoffman Foundation; the German Research Council; and NYSTEM.