Six new genetic risk factors for Parkinson's identified using gene chip

A new study led by researchers from the National Institutes of Health details how a state-of-the-art gene chip led to the discovery of six new genetic risk factors for Parkinson's disease, potentially providing a better understanding of the disorder and paving the way for new treatment strategies.

NeuroX - an advanced gene chip - helped researchers identify six new genetic risk factors for Parkinson's.
Image credit: National Human Genome Research Institute

The research team, including senior study author Andrew Singleton, PhD, a scientist at the National Institute on Aging, recently published their findings in the journalNature Genetics.

Parkinson's disease is a degenerative neurological disorder affecting more than 500,000 people in the US. Every year, approximately 50,000 more are diagnosed with the disorder, and these numbers are expected to increase along with the aging population.

The exact cause of Parkinson's disease is unclear. However, recent research has identified a number of genes believed to increase a person's susceptibility to the disorder.

In this latest study, Singleton and colleagues set out to add to these findings by conducting a large-scale meta-analysis of existing genome-wide association studies, involving 13,708 individuals with Parkinson's disease and 95,282 controls.

The team collaborated with numerous public and private organizations to gather the data, including the US Department of Defense and the Michael J. Fox Foundation.

Discovery of new pathways controlling the serotonergic system

With the aid of new methods, a research team at Karolinska Institutet have developed a detailed map of the networks of the brain that control the neurotransmitter serotonin. The study, published in the scientific journalNeuron, may lead to new knowledge on a number of psychiatric conditions and the development of new pharmaceuticals.

The neurotransmitter serotonin controls impulsivity, mood and our cognitive functions, among other things, and comes from the serotonergic neurons - the neurons that produce serotonin. So that we have good mental healthand normal behaviour, it is important that there is correctly regulated activity among these neurons. The activity is governed by other neurons from different regions of the brain via direct links, known as synapses, on the serotonergic neurons. Imbalance in the serotonergic system can lead to depression, Parkinson's disease,schizophrenia and autism, among other things.

So far it has been impossible to study in detail how different types of nerve cells are interlinked and how the brain's networks control behaviour. Consequently, there has also been a lack of knowledge of which nerve cells control the activity of the serotonergic neurons. But with the help of new methods, researchers can now investigate how the various networks of the brain are organised and how they work. The research team, led by Konstantinos Meletis of the Department of Neuroscience, has established which networks of the brain control the serotonergic neurons.

"We have been able to create a new type of map of the neurons' contacts and discovered new pathways that control the serotonergic system. These networks were previously unknown and are very interesting in terms of how they help us to understand how the serotonergic system works, which could also help us to understand certain mental illnesses," Konstantinos Meletis explains.

In order to map out which neurons have direct contact with serotonergic neurons, the researchers established a method in which these cells were marked with a rabies virus which produced a fluorescent marker. Via genetic manipulation, the rabies virus was then spread to all of the neurons directly linked to the serotonergic neurons. The researchers thereby gained a very detailed, three-dimensional image of the networks of the brain that control serotonin. Using optogenetics, a method in which light is used to control the activity of neurons, the researchers were then able to manipulate select networks and thus study their effect on the serotonergic neurons.

Via mapping, the researchers discovered a network in the frontal lobe which is associated with cognition and well-being and which controls the serotonergic neurons. Researchers also found that serotonin can be controlled from new types of neurons in the basal ganglia, an area of the cerebrum which among other things controls movement, well-being and decision-making; a discovery which may have significance for conditions such as Parkinson's disease.

"We are very optimistic that the revolution we are now seeing in brain research could also lead to entirely new and effective medicine in the field of psychiatry," Konstantinos Meletis explains.

Aug. 8, 2014

http://www.medicalnewstoday.com/releases/280762.php

The Health Benefits Of Learning Tai Chi

Each and every one of us can benefit from learning Tai Chi. This ancient Chinese art has been described as “meditation in motion” and is known to prevent and treat many health problems, as documented by several studies.

Tai chi is a practice that focuses on movements originating from the torso. Why is this important, and how do we lose this capability as we get older? Here is some insight, as presented by Synerchi Publishing:

“An early Tai Chi master once wrote that the ultimate purpose of learning Tai Chi was to live forever in the spring season of your life. Tai Chi is not just for longevity, but also for robustness, even at an old age. The health benefits of Classical Tai Chi may be viewed from several different angles and at different levels, all of which tie in strongly with the practice of Internal Discipline.

When examining the movements of very young children, we see that their movements of arms and legs often originate from their torso, their movements are relaxed and without tension. As we grow older our movements tend to concentrate on our arms, legs and shoulders and less on our torso: also, tension and stiffness start to creep into our movements. Gradually, we lose touch with the torso. We can only do simple movements such as the popular ab exercises but cannot perform the subtle, intricate, and powerful movements that the torso inherently is capable of. We talk about the dexterity of hands or feet, not knowing that the torso can be developed to have just as much dexterity, but think of the torso as a dull part of the body.

Eventually, stagnation in the torso sets in. We often see the elderly walking with a shuffle—the walking movement no longer extends into the torso. With all the major organs and complex circulatory system residing in the torso, it’s easy to understand the adverse effect of inaction and stagnation of the torso on the health of the body. One may assert that the onset of internal rigor mortis actually precedes death!”

If you want to maintain youthfulness of internal body systems, you must learn to initiate movements from the internal core of the body, to cultivate your body’s internal energy. Once we’re able to regain our connection with the torso, our body starts to work more effectively and efficiently, resulting in better health.

“Classical Tai Chi may be considered as a means to return to childhood. The Internal Discipline of the Form movements first tunes the nervous system in the body so that the complex and powerful internal movements will become natural and spontaneous. In China, a healthy and well-tuned nervous system is considered to be paramount to a healthy body. That is the importance of Qi (see more about Qi here). Physically, the internal movements penetrate to the deep recesses of the torso, stimulating and invigorating the organs and the circulation systems in the torso. Enhancement of the function of the intestine and kidney are immediate when tai chi is played with Internal Discipline. Other benefits are more long term.”

Our Western way of exercising can be difficult on the body especially long-term and as we get older. Here is how Tai Chi helps:

“Modern exercise routines, including martial arts, are long on external movements and short on internal movements, in other words, exercising the parts of the body which are already over-used for an active person while neglecting the portion of the body which needs exercise. Worse yet, these routines often subject the shoulder, knee, the back and other joints with ill-conceived repetitive, unnatural movements. No wonder many active people eventually develop joint problems. Classical Tai Chi, through the experience of multi-generations of practitioners who practice from a young age until the end of life, fully grasp the importance of proper postures and movements to protect and strengthening the practitioner’s joints for long term, repetitive practice.

Paving a Path for Cognition Treatment

FoxFeed Blog

Posted by  Maggie McGuire, August 07, 2014

Multi-tasking, focusing attention and remembering can become difficult for some people with Parkinson’s. These symptoms may be a sign of mild cognitive impairment with Parkinson’s disease or PD-MCI. There is no treatment available right now, but The Michael J. Fox Foundation is paving a path to get pharmaceutical companies interested in this part of PD and make approvals from the U.S. Food and Drug Administration (FDA) easier for when a drug is ready.

Two members of our research team with other key opinion leaders recently published a paper outlining the outcomes of their meeting with Parkinson’s research stakeholders and the FDA about PD-MCI. While PD-MCI therapies have made it to clinical trials, none were ever brought to FDA review for market approval. Therefore, there was little instruction for study sponsors.

“With other indications, you know what tests to use, what patient populations to test, what outcome measures the FDA will accept,” said Jamie Eberling, PhD, senior associate director for research programs. “With PD-MCI there is no precedence, so researchers didn’t know what to do.”

That uncertainty is discouraging to pharmaceutical companies. To de-risk the environment, MJFF gathered the FDA, the National Institutes of Health and leading experts in cognition.

One of the most impactful outcomes of that meeting is the understanding that the FDA is open to evaluating PD-MCI drugs measured with different scales. Physicians and researchers use numbered scales (such as Hoehn and Yahr) to measure symptom progression. There is no best practice scale for PD-MCI, but MJFF is working on that, too. In the meantime, drug developers can choose which scale they think is most appropriate for their study population and the drug they’re testing.

Additionally, the FDA wants to see that a PD-MCI drug leads to functional improvement. Rather than relying only on a scale, regulatory officials said they would review quality-of-life measurements as well. In other words, they want to know that people with PD-MCI are living better after taking the drug.

“The FDA will take a patient-centered approach and value the impact on quality of life that a PD-MCI treatment could have, which is good news for the patients and the research field,” said Lona Vincent, an author and senior associate director of research partnerships. “Several companies have expressed interest in pursuing PD-MCI drug development since our meeting.”

How do you maintain a healthy diet?

Healthy Diet

A healthy diet with plenty of water is the foundation for good health, regardless of whether or not you have PD. However, for those with PD, it is even more important. The reason why it is so critical for those with PD is that healthy eating can help keep your bones strong, thus decreasing the likelihood of a fracture if you fall. It also helps you fight constipation, which is common with PD.

The following are a few guidelines for healthy eating:

• Eat a variety of foods to get the energy, protein, vitamins, minerals and fiber you need for good health.
• Balance the food you eat with physical activity.
• Maintain or improve your weight to reduce chances of having high blood pressure, heart disease, stroke, certain cancers and most common types of diabetes.
• Choose a diet with plenty of grain products, vegetables, and fruits, which provide vitamins, minerals, fiber, and complex carbohydrates and which can help you lower your intake of fat.
• Choose a diet low in fat, saturated fat, and cholesterol to reduce your risk of heart attack, certain types of cancer, and to help you maintain a healthy weight.
• People with PD often lose weight without meaning to, due to nausea, loss of appetite, depression, and slowed movement. Unplanned weight loss together with malnutrition can lead to an weakened immune system, muscle wasting, loss of vital nutrients and risk for other diseases.
• Reduce your sugar intake! A diet with lots of sugar can have too many calories and too few nutrients. It can also contribute to tooth decay.
• Reduce how much salt and sodium you eat to help reduce your risk of high blood pressure.
• Drink alcoholic beverages in moderation as they have empty calories and little to no nutrients. Drinking alcohol can also cause many health problems and accidents.

What are some common nutritional concerns for people with PD?

 1. Bone thinning

• Studies have shown that people with PD are at increased risk for bone thinning.
• As PD advances it can increase the likelihood of falls.
• For those with PD, it is especially important to eat meals that provide the bone-strengthening nutrients including: calcium, magnesium, vitamins D and K.
• Regular exposure to sunlight is also important, as it increases vitamin D in the body and serves as a bone-strengthening agent.
• Walking and other weight-bearing exercises can also help in keeping bones strong and less likely to fracture or break.

2. Dehydration

• PD medications can raise the risk for dehydration leading to: confusion, weakness, balance problems, respiratory failure, kidney problems and death.
• Drink plenty of fluids throughout the day to avoid dehydration.

3. Bowel impaction

• PD can slow the movement of the colon, thus causing constipation.
• Therefore, you must get enough fiber in your diet.
• If the constipation does not get resolved it can lead to bowel impaction where a mass of dry, hard feces becomes impossible to pass normally.
• When bowel impaction occurs it may require hospitalization and even surgery.

Did you know that in the United States alone, dehydration is responsible for 1.8 million days of hospital care each year (about ten days per patient) and costs more than $1 billion annually?

4. Unplanned weight loss

• People with PD often lose weight without meaning to, due to nausea, loss of appetite, depression and slowed movement.
• Unplanned weight loss along with malnutrition can lead to a weakened immune system, muscle wasting, loss of vital nutrients and risk for other diseases and possibly even death over an extended period of time.

5. Medication side effects

• While medications play an important role in managing the symptoms of PD they may also have unwanted side effects.
• Taking more than one medication may increase the level of unwanted side effects.
• Common side effects include:
  • Nausea
  • Appetite loss, often followed by weight loss
  • Edema (fluid retention)
  • Compulsive eating and weight gain
  • Talk to your doctor if you are experiencing anything unusual.

6. Protein-levodopa interaction

• One of the more important medications used to treat PD is levodopa.
• However, levodopa must compete for absorption from the small intestine with proteins in food, and it may be necessary to take care with the timing of meals and medications.

Parkinson's Disease Foundation Awards $1.3 Million in Research Grants to Help Solve, Treat and End Parkinson's Disease

PDF Press Releases

More Than 30 Scientific Projects Chosen for Potential to Improve the Lives and Futures of People Touched by Parkinson's

- Jul 24 2014

The Parkinson's Disease Foundation® (PDF®) is pleased to announce $1.3 million in funding for more than 30 investigator-initiated research projects to help solve, treat and end Parkinson's disease.  Chosen through a competitive application process, the grants reflect PDF's continued commitment to improving the lives and futures of people touched by Parkinson's disease.  Browse research grants below or by visiting www.pdf.org/results_funded.   

"The Parkinson's Disease Foundation, through this latest selection of research grants, renews its most important promise to the community: to understand and help find the cure for Parkinson's disease, and for as long as that search continues, to ensure that those families and individuals who live with Parkinson's disease are able to achieve and maintain the best quality of life," noted PDF President Robin Anthony Elliott.

The research projects are chosen by PDF's Scientific Advisory Board led by Acting Chair Un Jung Kang, M.D., and PDF Scientific Director Stanley Fahn, M.D., and including several scientific experts and PDF-trained patient advocates.  The projects are funded through PDF's International Research Grants Program, which supports innovative ideas of early-career scientists and its Fellowships and Career Development program, which supports training for future leaders in Parkinson's research and care.

Malú G. Tansey, Ph.D., of Emory University School of Medicine, and Yoland Smith, Ph.D., of Yerkes National Primate Research Center at Emory, are recipients of a PDF-funded International Research Grant, which they are using to study the role of inflammation in Parkinson's disease, with the goal of advancing treatments.  Brain scans show that people with Parkinson's disease have more inflammation in their brains than is normal, and population studies suggest that drugs to treat inflammation may lower Parkinson's disease risk.  Dr. Tansey's research group has already shown the potential of an anti-inflammatory drug called XPro1595 to penetrate into the brain to lessen and slow brain cell degeneration in rodents.  The PDF-funded study will test the drug in monkeys exposed to a toxin called MPTP.  If XPro1595 is effective in reducing or delaying Parkinson's disease-like symptoms, it will be an important step in moving this drug toward clinical trials in humans.

"Scientists in today's competitive funding environment face the possibility that our most promising ideas may go unexplored.  This is what makes funding from PDF so crucial," noted Dr. Tansey.  "PDF funding ensures that no stone – such as the potentially promising compound we have identified – goes unturned in the search for more effective treatments for Parkinson's disease."

Damien J. Ellens, M.D., a recipient of a PDF Postdoctoral Research Fellowship, working with mentor Daniel K. Leventhal, M.D., Ph.D., at the University of Michigan, is using a new technique called optogenetics to better understand how dopamine impacts movement in Parkinson's disease.  It is well known that the chemical messenger dopamine controls the body's normal movements, and when lost, leads to movement symptoms in Parkinson's disease.  Although most drugs used to treat the movement symptoms of Parkinson's disease do so by replacing dopamine, we still do not understand exactly how these drugs work.  Dr. Ellens is focusing on a less-studied aspect of dopamine, its role in helping us to learn new movement.  He will study the dopamine neurons in rats as the rats learn a new motion.  With millisecond precision, he will observe how dopamine contributes to the ability of rats to learn the new movements versus how it allows them perform the movements.  Understanding how the distinct functions of dopamine contribute to the motor symptoms of Parkinson's disease may allow scientists to design new drugs that more effectively ease symptoms and minimize side effects.

Browse all PDF-funded investigator-driven Parkinson's disease research projects below and learn more about them by visitingwww.pdf.org/parkinson_research_grantees.  Learn more about additional Parkinson's disease research funded by PDF in 2014 by visitingwww.pdf.org/results_funded.  

International Research Grants | $742,500

Epigenetic Dysregulation in Levodopa-induced Dyskinesia* 
David Anderson, Ph.D., and Jay Schneider, Ph.D.,Thomas Jefferson University

Elucidation of the Role of Cholinergic Interneurons in Levodopa-induced Dyskinesias*
Tomas Björklund, Ph.D., Lund University, Sweden

Interaction of LRRK2 and Tau in Mediating Neurodegeneration in Mouse Models of Parkinson’s Disease*
Darren Moore, Ph.D., Van Andel Research Institute

Identifying Connectivity Changes with Deep Brain Stimulation in Parkinson’s Disease*
Matthias Schröeter, M.D., Ph.D., and Karsten Müller, Ph.D., Max Planck Institute for Human Cognitive and Brain Sciences, Germany

Novel Insights into the Properties and Fate of Naturally Secreted Alpha-synuclein
Georgia Sotiropoulou, Ph.D., University of Patras, Greece

Striatal CaV1.3 Calcium Channel Silencing as a Neuroprotective Target for Levodopa-induced Dyskinesias
Kathy Steece-Collier, Ph.D., and Fredric P. Manfredsson, Ph.D., Michigan State University

Imaging Impulse Control Disorders in Parkinson’s*
Antonio Strafella, M.D., Ph.D., Toronto Western Hospital, Canada

Neuroprotection by XPro1595 in a Chronic MPTP Monkey Model of Parkinson’s
Malú Tansey, Ph.D., and Yoland Smith, Ph.D., Emory University

Dysfunctional Signalling Mechanism of Neurotransmission in Parkinson’s Disease
Zhenyu Yue, Ph.D., Icahn School of Medicine at Mount Sinai

Postdoctoral Research Fellowships | $300,000

Functional Study of the Newly Identified Autosomal Recessive Early-onset Parkinsonism-associated Mutation in Sac1 Domain of Synaptojanin1
Mian Cao, Ph.D., mentor: Pietro De Camilli, M.D., Yale University

Optogenetic Dissection of the Role of Dopamine in Fine Motor Control
Damien J. Ellens, M.D., mentor: Daniel K. Leventhal, M.D., Ph.D., University of Michigan

Functional Analysis of Dopamine-dependent Circuits Activity in Parkinson’s Disease
Nan Li, Ph.D., mentor: Alan Jasanoff, Ph.D., Massachusetts Institute of Technology

Cell-specific Functions of the Globus Pallidus in the Basal Ganglia: Distinct Implications in Normal Behavior and PD
Amelie Soumier, Ph.D., mentor: Aryn H. Gittis, Ph.D., Carnegie Mellon University

In Vivo Modulation of Alpha-synuclein Phosphorylation: Tracking Aggregates in the Living Mouse Brain
Kateri Spinelli, Ph.D., mentor: Vivek K. Unni, M.D., Ph.D., Oregon Health & Science University

A Novel Function of PINK1/Parkin Pathway in Regulating Oxidative Phosphorylation through mRNA Localization & Translational Control
Zhihao Wu, Ph.D., mentor: Bingwei Lu, Ph.D., Stanford University School of Medicine 

Collaborative Fellowships | $142,500

PDF-ABF Clinician-Scientist Development Award | $52,500 (per year for three years)
(In partnership with the American Brain Foundation)
Parkin Overexpression as a Therapeutic StrategyAmber Van Laar, M.D., mentor: J. Timothy Greenamyre, M.D., Ph.D., University of Pittsburgh Medical Center

PDF-PSG Mentored Clinical Research Award | $50,000
(In partnership with the Parkinson Study Group)
A Functional MRI Study of Dopamine’s Effects on the Stability & Flexibility of Working Memory in Parkinson’s
Robert White III, M.D., Ph.D., mentors: Jill Ostrem, M.D., and Mark D’Esposito, M.D., University of California, San Francisco

PDF-HHMI Medical Research Fellowship | $40,000
(In partnership with the Howard Hughes Medical Institute)
Noninvasive Stimulation of Functional Neural Networks for Remote Brain Modulation & Tremor Reduction in Parkinson’s Disease
David Fischer, mentor: Alvaro Pascual-Leone, M.D., Ph.D., Harvard Medical School

Côté Clinical Genetics Initiative | $110,000

Generation and Characterization of Purified Induced Pluripotent Stem Cell-derived Dopaminergic Neurons to Study Monozygotic Twins Discordant for Parkinson’s
Aiqun Li, Ph.D., mentor: Scott A. Noggle, Ph.D., New York Stem Cell Foundation

Molecular Basis of Substantia Nigra Dopamine Neuron Vulnerability in Parkinson’s Disease
Ping-Yue Pan, Ph.D., mentor: Zhenyu Yue, Ph.D., Icahn School of Medicine at Mount Sinai

Summer Student Fellowships | $48,000

Quantitative Analysis of Alpha-synuclein in Various Brain Regions of Parkinson’s Disease Mouse ModelHanan Baker, mentor: Marie-Francoise Chesselet, M.D., Ph.D., University of California, Los Angeles

Clinical Subtypes of Parkinson’s & Longitudinal Trend of Disease ProgressionSeyed-Mohammad Fereshtehnejad, M.D. mentor: Ronald Postuma, M.D., M.Sc., McGill University, Canada

PINK1-AIF Interaction & Implications in PD PathogenesisFadi Hage, mentor: David Park, Ph.D., University of Ottawa, Canada

Can Sensory Attention Focused Exercise (PD SAFEx) Improve Balance Control & Proprioception in PD?Shannon Lefaivre, mentor: Quincy J. Almeida, Ph.D., Wilfrid Laurier University, Canada

Genetic Variation and Cognitive Impairment in People with Parkinson’s from UruguayAndrés Lescano, M.D., mentor: Ignacio Fernandez Mata, Ph.D., University of Washington

Role of Cognition in Reversing Motor Deficits in PDCharles Marquardt, mentor: Michael W. Jakowec, Ph.D., University of Southern California

Oscillatory Activity in the Subthalamic Nucleus in a Rodent Pharmacological Model of Parkinsonian TremorSamantha Podurgiel, mentor: John Salamone, Ph.D., University of Connecticut

Metabotropic Glutamate Receptor 4 Positive Allosteric Modulators Attenuate LPS-Induced Inflammation in Microglia CellsRanjani Ponnazhagan, mentor: David Standaert, M.D., Ph.D., University of Alabama at Birmingham

Methylene Blue as a Treatment for Motor & Cognitive Deficits in a Rodent Model of Parkinson’sElizabeth Smith, mentor: Hongjoo Lee, Ph.D., The University of Texas at Austin

Pathogenic Interactions Between Alpha-synuclein & Trichloroethylene In VivoRachel Tang, mentor: Edward A. Burton, M.D., D.Phil., University of Pittsburgh

Role of Basal Ganglia in Sensorimotor TransformationPouneh Vaziri, mentor: Robert Chen, M.B.B.Chir., M.Sc., Toronto Western Hospital, Canada

Impact of Medical Care Structure & Provider Availability on Outcomes in Parkinson’s DiseaseJonathan Woo, mentor: Allison Willis, M.D., University of Pennsylvania

*Denotes second year of funding

About Parkinson's Disease Parkinson's disease is a progressive neurological disorder that affects nearly one million people in the United States and seven to 10 million people worldwide.  Although promising research is being conducted, there is currently no cure for Parkinson's disease.

About PDF Research
The Parkinson's Disease Foundation® (PDF®) is committed to funding the highest caliber of science to solve, treat and end Parkinson's disease.  Since 1957, PDF has dedicated $105 million to research, which has contributed to major advances in science such as the discovery of genes linked to Parkinson's disease and development of levodopa.  As part of its funding, PDF is particularly focused on developing a strong pipeline of future leaders in research and care, and remains the largest private funder of specialized movement disorder training in the United States.  In 2014, PDF is funding three research centers, 39 scientific projects and training for nine clinical fellows, and is supporting more than 15 scientific meetings, conferences and professional development awards for students.  A full list of this year's research projects is available on the PDF website atwww.pdf.org/results_funded.

About the Parkinson's Disease Foundation (PDF)
The Parkinson's Disease Foundation® (PDF®) is a leading national presence in Parkinson's disease research, education and public advocacy.  We are working for the nearly one million people in the US who live with Parkinson's disease by funding promising scientific research while supporting people living with Parkinson's disease through educational programs and services.  Since its founding in 1957, PDF has dedicated over $105 million to fund the work of leading scientists throughout the world and over $44 million to support national education and advocacy programs.

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Source Date: Jul 24 2014

To Inform or Not to Inform? That Is the Question for Genetics Researchers

FoxFeed Blog

Posted by  Maggie McGuire, August 05, 2014

Researchers need to know the genetic profiles of their study participants to understand more about how certain mutations manifest disease. But do the participants have to know?

A group of 35 Parkinson’s disease (PD) researcherspublished today in Genetics of Medicine the different answers to that question among sites investigating mutations in the LRRK2 gene, the greatest known genetic contributor to PD. Investigators from The Michael J. Fox Foundation-sponsored LRRK2 Cohort Consortium authored the letter to the editor.

The consortium spanned nine countries on four continents. People with PD and their family members were screened for a LRRK2 mutation, and researchers conducted a more thorough investigation on carriers and a subset of those without mutations.

“The study design raised an ethical question: Should the genetic testing results be reported to participants?” the authors wrote. People with Parkinson's who carry the mutation are not treated differently than non-carriers with PD, and there are not yet preventative therapies to offer people with the mutation who do not have PD.

In general, mutations in the LRRK2 gene account for less than five percent of PD cases, but that number jumps in certain ethnic populations; LRRK2 mutations are associated with 18 to 40 percent of PD cases among those of Ashkenazi Jewish or North African Berber descent. Adding to the complexity is the unknown “penetrance” or association between a mutation and disease onset; estimates range from 24 to 80 percent.

LRRK2 Cohort Consortium sites in the United States did not offer genetic results to participants with PD, but Israeli sites concluded it would be unethical not to provide such information and therefore informed all PD participants who requested their results. Most study sites did not offer results to non-PD participants unless they first received genetic counseling. The Toronto team stopped offering these results after they felt participants had trouble grasping the information.

The letter’s authors outline the arguments for each side: Knowing one’s genetic risk may be distressing. However, many feel that this data is the property of the participants and they should be allowed to receive or refuse it as they prefer.

“It is true that presently there is no definitive action one can take to offset genetic risk for Parkinson’s disease,” said Brian Fiske, PhD, vice president of research programs at The Michael J. Fox Foundation. “However, individuals who do choose to learn their genetic status can play an important role in teaching researchers about the disease and possible treatments.”

The MJFF-sponsored Parkinson’s Progression Markers Initiative is enrolling people with the LRRK2 mutation, both with and without PD. 

How You Can Cope With Anxiety and Stress

A few years ago, I faced a dark period in my life. My mother was dying of cancer and the stress I was experiencing seemed too overwhelming to control. My medicines were not working nearly as well and my positive attitude was waning. It all began to take a toll on my body.

One Sunday afternoon I was watching television when out of nowhere these thoughts started racing through my head. It was as if 200 channels were playing at once. The flashing images were dizzying and upsetting. My pulse raced and my heart pounded. I was terrified, thinking I was having a heart attack.

I tried my best to slow my mind with deep breathing, calming thoughts, soft music and meditation. Only after about 40 minutes of focusing on my breath and visualizing calming images was I able to return to a more serene state of mind.

Afterward I realized that the buildup of stress over the previous weeks---from work, my mom's death, and my own attitude---led to the panic attack. Since this episode, I have learned how to better manage stress and to reduce the triggers that make me anxious. That was the first and only panic attack I have ever had.

Stress reducers

Reducing stressors in life is not always easy. You might need to take a closer look at your life to find what needs to change. Sometimes just reducing the negative influences in your life can make a big difference. Here is what I do to reduce stress and overcome anxiety---and what you can try, too.

Turn off the news. Overexposure to events that are beyond your control can create tension and worry.

Eliminate violent and mindless TV and stressful video games. Use that time to engage in a hobby or something you enjoy.

Minimize exposure to negative people. Instead, connect with people who uplift you.

Learn some relaxation techniques. Meditation, yoga and deep breathing can help restore a sense of calm. Seek a yoga class tailored to Parkinson's patients.

Seek solace in music. Try classical, soft rock, nature sounds or alternative. Set up a comfortable listening area where you can fully enjoy the moment. Stay passionate. If Parkinson's takes something you love away or care about, find a hobby to replace it. If you can no longer paint, pick up a camera and take pictures or learn to sing. Stay open-minded and resilient. This will help you handle adversity. Exercise away the anxiety. Talk to your doctor or physical therapist about setting up an exercise regimen that meets your health needs. Socialize. Nothing can empower you like a feeling of camaraderie. Get involved with a community organization, a support group, or a charity that you believe in.

Learn to laugh. Keeping a sense of humor is a sure way to beat anxiety. Watch a funny video and read something that makes you laugh every day.

Remember, anxiety and depression often go together. But the symptoms of anxiety can include: feelings of panic, fear and restlessness, sleep disturbance, poor concentration, palpitations, shortness of breath, irritability, and dizziness.

If you feel that you are totally overwhelmed by your feelings, consult with your physician. He or she can refer you to a mental health professional. There is no shame in seeking help, when you need it. Everyone deals with his or her anxiety differently.

Ultimately, finding balance in your mind and body will help you cope with the daily stresses of life. This may mean limiting your exposure to environmental stressors or using complementary therapies. Such approaches are wonderful ways to lower anxiety, lower blood pressure, and improve your all-around health.

Finally, remember, that your outlook and attitude are vital to everything you do, and keeping a positive attitude can be contagious. I promise you, staying positive makes living with Parkinson's disease easier and more enjoyable. If you are able to incorporate the above tips into your life over time, you may find that anxiety will be a thing of the past.

The End for Levodopa Phobia

New Study Shows Sinemet is a Safe Initial Therapy for Treatment of Parkinson’s Disease

You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Center for Movement Disorders & Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.
In November 2011 we wrote about an important phenomenon called levodopa phobia, or avoidance of dopamine as a treatment for Parkinson’s disease. Many Parkinson’s disease patients and family members have been unnecessarily alarmed by the continuing reports that Sinemet and/or Madopar (European Sinemet) may accelerate disease progression, and that doses and drug intervals should be limited. These reports have unfortunately been fueled by sparse human evidence. Patients need to be aware that dopamine replacement therapies such as Sinemet and Madopar remain the single most effective, and single most important treatment for Parkinson’s disease worldwide. This month’s “What’s Hot” column will update the previous 2011 column, and focus on the new evidence published in the Lancet this month by the PD MED Collaborative Group.

Neurology previously published an article in 2011 citing that there was important evidence that dopamine replacement therapy is not toxic, and does not accelerate disease progression. Parkkinen and colleagues at Queen Square in London examined pathology in 96 post-mortem Parkinson’s disease brains, and paired the tissue with clinical information including levodopa use. The study concluded that in the human condition “chronic use of L-dopa does not enhance progression of Parkinson’s pathology.”

In an accompanying editorial, two prominent neurologists in the field pointed out that there “remains lingering concerns as to whether levodopa is toxic to dopamine neurons and accelerates the degenerative process.” The science quoted to support these claims has included levodopa undergoing auto-oxidation, and forming reactive oxygen species and toxic protofibrils. Additionally, the science includes a classical experiment that showed when levodopa was mixed with brain cells placed in a dish, there was toxicity. The research, however, has fallen short in demonstrating toxicity of the drug in the human form of Parkinson’s disease. There now exist broad levels of evidence from many studies across many countries (including most recently the ELLDOPA study) that levodopa is extremely beneficial to the human patient, and that levodopa has had a positive effect on disease course. Sinemet was recently reported as the most commonly administered drug among 7000+ patients being followed longitudinally in the National Parkinson Foundation Quality Improvement Initiative study. Expert practitioners who reported in this database utilized levodopa more than any other drug-- including dopamine agonists, and they used levodopa more (not less) as disease durations increased.

The newest study published in this month’s Lancet included newly diagnosed patients randomized to receive a dopamine agonist, a monoamine oxidase inhibitor (MAOBI) or levodopa. The primary outcome was the mobility dimension on the Parkinson’s disease questionnaire (PDQ-39) quality-of-life scale which is a validated way to measure meaningful improvements. There were 1620 patients randomized and followed. The three year follow-up revealed the PDQ-39 mobility scores were better in levodopa as compared to the other two groups. Follow-up at 7 years revealed levodopa was the best therapy, but there was a small difference favoring initial therapy with the MAOBI when this drug was compared to a dopamine agonist. The treatment related side effects were less in levodopa.

Over the past two decades the trendy phenomenon, referred to as levodopa phobia (intentionally avoiding prescriptions for levodopa) likely impeded the best clinical care for many Parkinson’s disease patients. An accompanying editorial to the recent Lancet article pointed out that levodopa phobia and also the favoring of agonist therapy was primarily driven by aggressive pharmaceutical marketing. The Lancet study revealed that all three therapies should be considered, but ultimately that the choice of drugs should be tailored to the individual patient. Patient-rated mobility in this study clearly favored initial levodopa therapy.

What all this adds up to for patients and for Parkinson’s sufferers is that Sinemet and Madopar should be considered safe and effective as initial treatments for Parkinson’s disease. The doses and intervals should be frequently adjusted by an experienced neurologist/practitioner in order to maximize benefits, and to tailor to individual symptoms. Patients and families should keep in perspective that the “talk” about levodopa being toxic and accelerating disease progression (levodopa phobia) can prove a major distractor to good care practices. Precious minutes in the doctor-patient relationship should not be wasted on these claims, and prescribers should not avoid or under-dose this critical therapy, especially in patients with treatable symptoms. Critics of Sinemet and Madopar will need to bring forward much stronger human data if they wish to change clinical practice. In the mean time, we need to serve our patients by sharing with them the weight of the evidence which strongly supports that levodopa replacement therapy is not toxic, does not accelerate Parkinson’s disease, and can be used safely as initial therapy.

Selected References:

Parkkinen L, O'Sullivan SS, Kuoppamäki M, Collins C, Kallis C, Holton JL, Williams DR, Revesz T, Lees AJ. Does levodopa accelerate the pathologic process in Parkinson disease brain? Neurology. 2011 Oct 11;77(15):1420-6. Epub 2011 Sep 14.

Olanow CW, Obeso JA. Levodopa toxicity and Parkinson disease: Still a need for equipoise. Neurology. 2011 Oct 11;77(15):1416-7. Epub 2011 Sep 14.

Fahn S. Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs Later L-DOPA. Arch Neurol. 1999 May;56(5):529-35.

Okun MS. An Important Update for Clinicians Treating Parkinson’s Disease Patients: Is This the End of Levodopa Phobia. New England Journal of Medicine Journal Watch, June, 2014.

Kurlan R. “Levodopa phobia”: A new iatrogenic cause of disability in Parkinson disease. Neurology 2005; 64: 923–24.

PD MED Collaborative Group. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson's disease (PD MED): a large, open-label, pragmatic randomised trial. The Lancet - 11 June 2014 DOI: 10.1016/S0140-6736(14)60683-8.