Our Parkinson's Place: 2014

Wednesday, December 31, 2014

ARIA Widens Sales Turf, NRX Skips A Beat, NDRM Triples On Parkinson's Study

Tuesday, December 30, 2014

NeuroDerm Parkinson's Drug Shows Promise In Mid-Stage Study

12/30/2014 9:52 AM ET

Clinical-stage pharmaceutical company

NeuroDerm Ltd. (NDRM: Quote), which went public in November, announced Tuesday topline results for a mid-stage study for its proprietary liquid levodopa/carbidopa (LD/CD) product candidates as a treatment for Parkinson's disease.

Following the announcement, the company's shares are skyrocketing more than 49 percent in early deals.

The company said the continuous, subcutaneous delivery of the liquid product candidates, ND0612H and ND0612L, led to clinically-significant plasma levodopa levels. The company added that ND0612H, the higher dose version, provided an effective

alternative to current treatments that require surgery.

"Maintaining consistent levodopa concentrations has been the most significant hurdle in Parkinson's disease therapy. The results from this study demonstrate that ND0612H can reach high LD plasma levels that, to date, could only be reached and maintained by products that require surgical intervention," said Sheila Oren, NeuroDerm's Vice President

of Clinical and Regulatory Affairs.

The phase IIa study was conducted on 16 patients with an advanced form of Parkinson's disease having motor fluctuations that was chronically treated with standard of care oral LD/CD. The primary endpoints of the study were to assess the safety

, tolerability and pharmacokinetics (PK) of six dose regimens of ND0612H and ND0612L.

The patients were treated with ND0612L (n=9) or ND0612H (n=7) for eight hours per day, for three consecutive days, with high and low doses of CD, and with adjunct oral entacapone. The LD/CD product candidates are continuously administered subcutaneously through a belt-worn pump.

The trial results showed that patients receiving ND0612H achieved maximum daytime levodopa plasma concentrations of 1,333ng/ml and 1,807ng/ml with oral entacapone added.

Meanwhile, patients receiving ND0612L achieved maximum daytime concentrations of 528ng/ml and 596ng/ml with oral entacapone added.

The company confirmed that all patients completed the study and treatment with ND0612L and ND0612H did not raise safety and tolerability concerns.

Rehovot, Israel-based NeuroDerm focuses on developing

drugs for central nervous system (CNS) diseases.

The company noted that it will now proceed with the clinical development of ND0612H and ND0612L in the U.S. and the European Union in 2015, based on the promising mid-stage trial results.

Parkinson's disease is a progressive neurodegenerative illness characterized by reduced dopamine in the brain, resulting in a debilitating decrease in the patient's motor

and non-motor functions. Its symptoms, such as trembling in the extremities and face, slowness of movement and impaired balance and coordination, worsen over time and gravely impact the patient's quality of life.

In Tuesday's regular trading session, NDRM is currently trading at $9.23, up $3.05 or 49.35% on a volume of 2.32 million shares. In the past 52-week period, the stock has been trading in a range of $5.67 to $9.45.

http://health.einnews.com/article/242017194/ItAVG8YB69zTAz2e

Sunday, December 28, 2014

Multimodal Imaging of rare Synucleinopathies.

Neurodegenerative diseases (NDD), such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), are progressive, disabling disorders, which pose an increasing burden on health care systems and societies. Despite remarkable progress in the understanding of their molecular pathogenesis, no causative or disease-modifying treatment is currently available. Aggregation of misfolded proteins is thought to play a crucial role in the initiation of the pathogenic cascades, but attempts to exploit this knowledge to develop novel treatments have so far not been successful, partly because the relationship between protein aggregation on the one hand and neuronal dysfunction and neurodegeneration on the other is still poorly understood and pathogenetically relevant biomarkers of protein aggregation are lacking.

In order to overcome this critical road-block, we have assembled an interdisciplinary consortium, consisting of world-leading experts in structural biology and ligand development, multimodal neuroimaging, animal models and clinical trials to develop a novel imaging system for combined simultaneous molecular and functional imaging (PET-MRI/fMRI) for two rare subtypes of parkinsonism caused by excessive accumulation of misfolded alpha-synuclein (αSYN), multiple system atrophy (MSA) and parkinsonism caused by mutations in the alpha-synuclein gene (SNCA), which will serve as proof-of-principle models for the more common and heterogeneous NDD like AD and PD. With the PET/MR technology and novel imaging biomarker development we will pioneer the monitoring of protein aggregation as a surrogate marker for therapeutic effects in the framework of individualized causative treatment. The central aspects of the work-flow including ligand design, software development and drug trials will be driven by three highly specialized SMEs, while imaging workflow, translation to animal models and clinical use will be implemented by top academic centers.

http://www.multisyn.eu

Fatigue and Depression

Fatigue can be described as an overwhelming sense of tiredness, a lack of energy and a feeling of exhaustion.
People with Parkinson's can experience fatigue at any time during their condition.
Although many people use the terms fatigue and sleepiness interchangeably, they are considered separate things.
Fatigue can be a physical, mental or an emotional feeling. Anybody can feel fatigued when they are working too hard, or when pressures at work or at home cause stress.
Fatigue can also be a symptom of an illness and it can be difficult to work out what may be causing it.
How can fatigue affect people with Parkinson's?
People with Parkinson's can experience fatigue at any time during their condition, and how it can affect them can change from day to day.
You may feel quite fit and able one day and then too tired to do much the following.
Many people with Parkinson's can also experience problems with sleeping at night, which can often leave you feeling tired and lethargic during the day.
Read more about sleep and night-time problems
Depression
If you're depressed, you may experience a range of symptoms, as well as low mood, for long periods of time. This includes fatigue.
You may feel tired, have difficulty sleeping and have a lack of interest in your usual activities. If you have fatigue and are concerned about depression, speak to your GP, specialist or Parkinson's nurse (if you have one).
Read more about depression and Parkinson's
Apathy
Fatigue may also imitate apathy, which may mean you lose interest in activities that you used to enjoy.
Apathy, like depression, needs to be diagnosed so it can be treated. You may find it helpful to speak to a mental health specialist or counsellor about it.
What can help with fatigue?
There are a number of things you can do to try to avoid fatigue or help reduce it.

¥ Try to take short, regular breaks at work. This can be as simple as making a cup of tea, having a chat with a colleague, or sitting back for a few moments with your eyes closed.
¥ Divide household tasks so that you do the jobs you can manage more easily.
¥ Try to get some regular exercise.
¥ Stay in involved with any hobbies and interests you have – boredom can lead to fatigue.
¥ Try to eat a healthy, balanced diet. Some people find that regular, healthy snacks help to keep their energy levels up.
¥ Pace yourself and understand your limitations.

What treatments are available?
Although it's natural to associate any health problems with Parkinson's, there may be other causes of fatigue unrelated to your condition.
It's important to discuss any feelings of fatigue with your GP, specialist or Parkinson's nurse.
So it is important to discuss any feelings of fatigue with your GP, specialist or Parkinson's nurse.
Together, you can look at what the cause of your fatigue is and discuss treatment options.
If your feelings of fatigue are related to other Parkinson's symptoms, it may be helped with Parkinson's medication. This will also help you manage your symptoms better, so you have more energy to do things that may otherwise be difficult.
It might be possible to manage fatigue with other, non-Parkinson's medication. We recommend that you discuss this carefully with your GP or specialist. In some cases non-drug treatments, such as cognitive behavioural therapy, may help.

- See more at: http://www.parkinsons.org.uk/content/fatigue-and-parkinsons#sthash.7iKdp8qx.7XvuuYan.dpuf

http://www.parkinsons.org.uk/content/fatigue-and-parkinsons

Saturday, December 27, 2014

The cause of prostate cancer may be linked to Parkinson's disease through a common enzyme

Prostate cancer affects more than 23,000 men this year in the USA however the individual genes that initiate prostate cancer formation are poorly understood. Finding an enzyme that regulates this process could provide excellent new prevention approaches for this common malignancy. Sirtuin enzymes have been implicated in neurodegeneration, obesity, heart disease, and cancer. Research published online in The American Journal of Pathology show the loss of one of sirtuin (SIRT1) drives the formation of early prostate cancer (prostatic intraepithelial neoplasia) in mouse models of the disease.

"Using genetic deletion we found that SIRT1 normally restrains prostatic intraepithelial neoplasia in animals. Therefore too little SIRT1 may be involved in the cellular processes that starts human prostate cancer," said Dr. Richard Pestell, M.D., Ph.D., MBA, executive Vice President of Thomas Jefferson University and Director of the Sidney Kimmel Cancer Center. "As we had shown that gene therapy based re expression of SIRT1 can block human prostate cancer tumor growth, and SIRT1 is an enzyme which can be targeted, this may be an important new target for prostate cancer prevention."

The researchers led by Dr. Pestell, created a mouse model that lacked SIRT1 and noticed that these mice were more likely to develop an early form of prostate cancer called prostatic intraepithelial neoplasia (PIN).

Other researchers had shown that SIRT1 can defend the cell against damage from free radicals. Pestell's group took the work further by showing that in this prostate cancer model, free radicals built up in cells lacking SIRT1. They showed that normally, SIRT1 proteins help activate a mitochondrial protein called SOD2, in turn activating those proteins to keep free-radical levels in check. When SIRT1 level are diminished, SOD2 is no longer effective at removing free radicals, allowing a dangerous build up in the cells, and leading to PIN.

"The next step," says first author Gabriele DiSante, Ph.D., a postdoctoral fellow in the department of Cell Biology at Jefferson, "is to determine if this is also important in the development of human prostate cancer."

Adapted by MNT from original media release

http://health.einnews.com/article/241641778/h7SRzTbK4RCNsF_2

YOUR HEALTH Health Day - ONLINE EDITION Methamphetamine Use Linked to Parkinson's Risk

Study also found women who took the drug had higher odds of the disease than men Posted: 12/26/2014 4:00 PM |

Study also found women who took the drug had higher odds of the disease than men.

FRIDAY, Dec. 26, 2014 (HealthDay News) -- People who use methamphetamine have a greatly increased risk of developing Parkinson's disease, a new study warns.

Researchers analyzed the medical records of more than 40,000 people in Utah. About 5,000 of that group were methamphetamine -- or "meth" -- users. Around 1,800 were cocaine users, and about 34,000 didn't use drugs, according to the researchers.

The study found that methamphetamine users were three times more likely to develop Parkinson's disease. Cocaine users didn't

have an increased risk of Parkinson's, the researchers said.

The study wasn't designed to prove that methamphetamine caused Parkinson's disease, but it did find a strong association between use of the drug and the development of the disorder.

The study was published recently in the journal Drug and Alcohol Dependence.

The researchers also found that women who use methamphetamine appear to be nearly five times more likely to develop Parkinson's than those who don't use drugs. However, further research is needed to confirm the gender difference, and to figure out why such a difference might exist, the study authors said.

"Typically, fewer females use meth than males do," senior study author Glen Hanson, interim dean of the University of Utah School of Dentistry and a professor of pharmacology and toxicology at the University of Utah, said in a university news release.

"Even though women are less likely to use it, there appears to be a gender bias toward women in the association between meth use and Parkinson's," he added.

The findings support a previous study that found a similar risk for Parkinson's among methamphetamine users in California.

Meth use is linked with a number of physical and mental health issues, including memory loss and serious dental problems, the study authors noted.

Parkinson's is a progressive movement disorder that typically begins at age 60 or older. Symptoms include tremors, rigid muscles and slowed movement. There is no cure for the disease, but medications and surgery can ease symptoms, the researchers said.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more about Parkinson's disease.

http://health.einnews.com/article/241587657/xsonbhq68YvwkYw2

Thursday, December 25, 2014

Tackling Parkinson's with targeted therapeutic vaccines

Clinical trials are about to begin on a new Parkinson's disease vaccine that could offer patients significant improvements over current treatments. The vaccine, developed through the FP7-funded SYMPATH project, may actually be able to modify disease progression, rather than simply providing symptomatic improvement.

Breakthrough could improve the lives of hundreds of thousands of people. Parkinson's disease is the second most common neurodegenerative disorder among the elderly; it has been estimated that there are around 1.2 million patients in Europe alone. There is currently no cure and existing therapeutic measures are only able to treat symptoms. The disease typically starts with non-motor symptoms, and progresses slowly but steadily to a debilitating state.

What is more, the provision of healthcare for the elderly has become a pressing social and economic concern. By 2025, more than 20 % of Europeans will be 65 or over, with a particularly rapid increase in the number of over 80s. An ageing population means increased incidences of physical, sensory and mental diseases. If Europe is to maintain manageable healthcare costs and ensure a decent quality of life for millions of its citizens, then diseases like Parkinson's must be tackled.

This has been the objective of the SYMPATH project. Although therapeutic vaccines have been the subject of intensive research for neurodegenerative disorders, no concept has as yet entered into clinical practice.

The new vaccine works by targeting a specific protein called alpha-Synuclein, which plays a key role in the onset and progression of Parkinson's as well as 'Multiple system atrophy' (MSA). MSA is a rare neurodegenerative disorder that progresses rapidly, usually leading to death within nine years. It is associated with the degeneration of nerve cells in specific areas of the brain, causing problems with movement and balance.

These randomised, placebo-controlled trials will be conducted in Vienna and Innsbruck, Austria. The trials aim to demonstrate the safety and tolerability of the vaccine, and researchers will also assess the vaccine's immunological and clinical activity in vaccinated patients.

SYMPATH builds on the fact that vaccines have a particularly attractive cost-effectiveness ratio. Their protection rate is usually high, side effects are minimal, and vaccines only need to be administered a limited number of times. The cost-medical benefits ratio of a therapeutic vaccine is therefore unlikely to be met by any other form of treatment currently under development. In this way, the SYMPATH project will help to meet public health needs and contribute to the sustainability of European healthcare systems.

The start of the clinical trial comes only a year after the SYMPATH consortium was launched, reflecting the high level of cooperation achieved between the expert partners. Scheduled to run until September 2017, the project has received nearly EUR 6 million in EU funding from the Seventh Framework Programme (FP7). AFFiRiS, located in Vienna, Austria, is the coordinator for the project's ambitious research programme. Project partners include five universities and three SMEs from across Europe.

Explore further: EU team launches clinical trial of Parkinson's vaccine

More information: SYMPATH: www.sympath-project.eu/

Wednesday, December 24, 2014

Understanding Parkinson's disease

11 hours ago • By Amy Fachman/Fremont Health

We rely on our brains for every movement we make, whether writing, walking, talking or even sleeping.

But a serious brain disorder like Parkinson’s disease can rob a person of the ability to do everyday tasks that many of us take for granted.

There’s no cure, but treatment can help. And researchers continue to seek new understanding to improve medical care.

Parkinson’s disease evolves gradually over time. The early signs may be barely noticeable. A person’s movements may change slightly. You might notice slowness, rigidity or difficulty balancing or walking. The person’s face may lack expression or handwriting may become small and cramped.

Eventually, these changes can become more severe and interfere with daily life. It might become harder to sleep, think, eat, speak, smell and make decisions. As the disease worsens, symptoms may become difficult to control.

Parkinson’s disease usually arises after age 50, but can also appear earlier in life. It affects about 600,000 people nationwide. As Americans age, the number of people with Parkinson’s disease is expected to rise dramatically.

Parkinson’s disease is a neurodegenerative disorder, which means that brain cells gradually malfunction and die. The disease damages brain cells that make a chemical called dopamine. The resulting dopamine shortage causes the movement problems that mark Parkinson’s disease.

Although researchers don’t yet understand what causes Parkinson’s disease, the body’s genes likely play some role. A number of genes have been linked to the risk of developing Parkinson’s.

But genes are only part of the picture. Scientists are searching for other factors that might lead to the disease. One goal of this research is to discover new targets for drugs that can slow disease progression.

If you notice any of the common signs of Parkinson’s disease, see a health care provider. Your doctor may refer you to a neurologist, a physician specializing in the nervous system. A careful exam and certain tests can help with diagnosis.

Parkinson’s disease affects everyone differently. Common symptoms include:

* Movement problems such as shaking or tremor, especially in the fingers, hand, arm or face.

* Rigidity, stiffness or slowness.

* Fatigue or problems sleeping.

* Problems standing or balancing.

* Trouble speaking or choosing words.

* Changes in handwriting.

* Difficulty completing simple tasks or making decisions.

* Inability to detect odors.

To treat Parkinson’s, doctors prescribe combinations of medicines that work to regulate dopamine in the brain. This helps free up people to move better and lessens the troubling movement problems of Parkinson’s.

A surgical procedure called deep brain stimulation is an option for some patients. In this approach, a small pacemaker-like system is placed in areas of the brain that control movement.

Research suggests that eating right and exercising may help reduce or delay symptoms. Scientists are studying how much and what kinds of exercise can most help improve patient health and quality of life.

Amy Fachman is public relations and marketing coordinator at Fremont Health.

Tuesday, December 23, 2014

SCIENTISTS CREATE PARKINSON’S DISEASE IN A DISH

A team of scientists led by The New York Stem Cell Foundation (NYSCF) Research Institute successfully created a human stem cell disease model of Parkinson’s disease in a dish. Studying a pair of identical (monozygotic) twins, one affected and one unaffected with Parkinson’s disease, another unrelated Parkinson’s patient, and four healthy control subjects, the scientists were able to observe key features of the disease in the laboratory, specifically differences in the patients’ neurons’ ability to produce dopamine, the molecule that is deficient in Parkinson’s disease. In addition, the scientists also identified a potential strategy for developing novel therapies for Parkinson’s disease.

Attributed to a combination of genetic and nongenetic factors, Parkinson’s disease has no completely effective therapy or cure. Parkinson’s disease is moderately heritable, but the mechanisms of this inheritance are not well understood. While genetic forms of the disease exist, sporadic forms are far more common.

“The unique scenario of identical twins, one with this disease and one without, allowed our scientists an unprecedented look into the mechanisms of Parkinson’s disease,” said Susan L. Solomon, NYSCF Chief Executive Officer. “Advanced stem cell research techniques allow us to push the boundaries of science and see what actually goes wrong at the cellular level, step by step during the disease process.”

DNA mutations resulting in the production of a specific enzyme called glucocerebrosidase (GBA) have been linked to a five-fold greater risk of developing Parkinson’s disease; however, only 30% of individuals with this mutation have been shown to develop Parkinson’s disease by the age of 80. This discordance suggests that multiple factors contribute to the development of Parkinson’s disease, including both genetic and non-genetic factors. To date, there has been no appropriate model to identify and test multiple triggers leading to the onset of the disease.

This image shows the neurons created as part of this experiment.

The scientists had the unique opportunity to study contributing factors to Parkinson’s disease through a set of identical twins, one of which has the disease. Credit New York Stem Cell Foundation.

In this study, published today in Cell Reports, a set of identical twins, both with a GBA mutation, provided a unique opportunity to evaluate and dissect the genetic and non-genetic contributions to the development of Parkinson’s disease in one twin, and the lack of disease in the other. The scientists made induced pluripotent stem (iPS) cells from skin samples from both twins to generate a cellular model of Parkinson’s in a dish, recapitulating key features of the disease, specifically the accumulation of α-synuclein and dopamine deficiency.

Upon analyzing the cell models, the scientists found that the dopamine-producing neurons from both twins had reduced GBA enzymatic activity, elevated α-synuclein protein levels, and a reduced capacity to synthesize and release dopamine. In comparison to his unaffected brother, the neurons generated from the affected twin produced less dopamine, had higher levels of an enzyme called monoamine oxidase B (MAO-B), and poor ability to connect with each other. Treating the neurons with molecules that lowered the activity of MAO-B together with overexpressed GBA normalized α -synuclein and dopamine levels in the cell models. This suggests that a combination therapy for the affected twin may be possible by simultaneously targeting these two enzymes.

“The subject of Parkinson’s disease discordant twins gave us an incredible opportunity to utilize stem cell models of disease in a dish to unlock some of the biological mechanisms of disease,” said Dr. Scott Noggle, NYSCF Vice President, Stem Cell Research and The NYSCF – Charles Evans Senior Research Fellow for Alzheimer’s Disease. “Working with these various different groups and scientists added to the depth and value of the research and we hope our findings will be applicable to other Parkinson’s disease patients and other neurodegenerative disorders.”

In this particular scenario, genetic and stem cell analysis identified an avenue for a potentially useful combination therapy for the twin affected by Parkinson’s disease and may be applicable more broadly to other Parkinson’s patients. While this case study is unique, this type of research and cellular analysis could yield further clues to all cases of genetic and sporadic Parkinson’s disease and other related neurological disorders.

About this Parkinson’s disease research

This study was conducted in collaboration with scientists at New York University Langone Medical Center including Dr. Melissa Nirenberg, Columbia University, Harvard University, the Icahn School of Medicine at Mount Sinai, Axion Biosystems, and Genzyme Corporation. Chris Woodard and Brian Campos of The New York Stem Cell Foundation Research Institute were the co-first authors of the study and Dr. Scott Noggle and Dr. Aiqun Li of The New York Stem Cell Foundation Research Institute and Dr. Sheng-Han Kuo of Columbia University Medical Center were the corresponding authors for the study.

Contact: David McKeon – New York Stem Cell Foundation
Source: New York Stem Cell Foundation press release
Image Source: The image is adapted from the New York Stem Cell Foundation press release
Original Research: Full open access research for “iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease” by Chris M. Woodard, Brian A. Campos, Sheng-Han Kuo, Melissa J. Nirenberg, Michael W. Nestor, Matthew Zimmer, Eugene V. Mosharov, David Sulzer, Hongyan Zhou, Daniel Paull, Lorraine Clark, Eric E. Schadt, Sergio Pablo Sardi, Lee Rubin, Kevin Eggan, Mathew Brock, Scott Lipnick, Mahendra Rao, Stephen Chang, Aiqun Li, and Scott A. Noggle in Cell Reports. Published online November 6 2014 doi:10.1016/j.celrep.2014.10.023

http://neurosciencenews.com/parkinsons-genetics-disease-in-dish-1500/

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