Parkinson's Drugs May Spur Compulsive Behaviors

MONDAY Oct. 20, 2014, 2014 -- Drugs commonly used to treat Parkinson's disease may raise the risk of so-called impulse control disorders, according to a new review.

These disorders include compulsive gambling, compulsive shopping and/or hypersexuality.

That increased risk was seen in a fresh review of a decade's worth of U.S. Food and Drug Administration (FDA) records.

"What we have here is a striking example of a major problem in drug safety," said study author Thomas Moore, a senior scientist with the Institute of Safe Medication Practices and a lecturer in epidemiology and biostatistics at George Washington University, in Washington, D.C. "And that is the issue of how drugs can sometimes provoke psychiatric side effects that actually make people behave in extremely destructive and abnormal ways."

Moore and his colleagues reported their findings online Oct. 20 in the journal JAMA Internal Medicine.

According to the American Parkinson Disease Association, these medicines are part of a powerful and effective class of drugs known as dopamine receptor agonists. These medications work by mimicking the activity of the brain chemical dopamine.

The study's authors stressed that these medicines are widely used to treat a range of illnesses, including Parkinson's, restless leg syndrome and patients diagnosed with high levels of the hormone prolactin -- which can cause impotence in men and can prevent pregnancy in women.

More than 2 million such prescriptions were filled during the last three months of 2012 alone, the researchers noted.

To explore any risk for the development of impulse control issues, the study authors analyzed FDA data on 2.7 million domestic and foreign adverse drug events reported between 2003 and 2012.

Of these, 1,580 events were specifically identified as involving what investigators categorized as "serious" impulse control scenarios, with about half involving American patients. The remaining cases involved patients in 21 other countries.

Nearly 45 percent of these events (710) were linked directly to the use of any of six different dopamine receptor agonist medications, with most involving male patients (more than 65 percent) at an average age of 55. The other 55 percent of cases were associated with the use of other medications, the study found.

More than 60 percent of the time, the impulse control cases involving dopamine receptor agonists were patients struggling with Parkinson's, while nearly a quarter involved patients with restless leg syndrome, the researchers said.

Breaking it down, the team identified 628 instances of pathological gambling, 465 cases of hypersexuality, and 202 examples of compulsive shopping.

"I should say that the risk for these events does not appear to be rare at all," said Moore. "These psychiatric side effects appear to occurring among at least 10 percent of patients. If you compare that with, say, the risk for suicide among patients who take antidepressant drugs, this is much higher. It's an astronomical rate, in terms of drug adverse event risk. And frankly I think I'm being conservative."

Joshua Gagne, an assistant professor of medicine with Harvard Medical School and Brigham and Women's Hospital in Boston, agreed that the increased risk could exceed 10 percent.

"The problem is that there is certainly a lot of underreporting of the problems we're talking about," he explained. "I suspect many affected patients never tell anyone. It's easy to imagine that a patient would be ashamed if they're losing a lot of money gambling or doing things that they generally don't want their family to know about, which suggests many may be keeping this issue a secret, leading us to underestimate the dimension of the situation."

Gagne, who wrote a commentary accompanying the new analysis, said a lot more research will be needed before the true risk is clearly defined.

"The thing to know," he added, "is that there aren't many treatment options for Parkinson's, for example, that work as well as these drugs. They're really a cornerstone of treatment, and it's important to have them as options.

"But while they should continue to be used, it's equally important to know what the risks are," Gagne said. "So, while more research is done, we need to encourage physicians and pharmacists and patients to discuss the concern, and to help patients be more open about it when these issues take hold."

http://www.drugs.com/news/parkinson-s-may-spur-compulsive-behaviors-53596.html

Israelis Discover Clear Link Between Diabetes And Parkinson’s Disease

Neurons

Health News 

Maya Yarowsky, NoCamels | Oct, 20 2014

Basing their research on previous studies that showed amylin is also found in the brain and is related to Alzheimer’s disease when it clumps together, Miller discovered that this same hormone could cause Parkinson’s in patients with diabetes. “Our findings led us to the hypothesis that if amylin is located in the brain it can also interact with other proteins and peptides in the brain,” Miller tells ISRAEL21c.

 

Dr. Yifat Miller

From here, Miller and her team observed how NAC, which is part of a protein called alpha-synuclein, led to the death of neurons at an atomic level. By mapping the atomic structure of NAC and showing how it aggregates itself throughout the brain, Miller revealed for the first time the clumping mechanism in the brain that leads to Parkinson’s disease. All that was left was for her and her team to show that the presence of amylin in the brain and pancreas, and its clumping habits, could be the explanation for why Type II diabetics are at higher risk of contracting neurodegenerative diseases.

The first step on the road to an effective Parkinson’s treatment?

Using sophisticated computer simulations to examine how NAC interacts with amylin in the brain, Miller was able to support her conclusion that the synergy between these elements is what explains the higher neurodegenerative risk for diabetes patients. “We propose that NAC and amylin aggregate together and kill neuron cells, and these aggregates lead to Parkinson’s disease,” says Miller, clarifying that its NAC and amylin taken together that increase the risk of developing the disease.

Miller’s findings on the NAC-amylin interaction were confirmed in experiments, and she hopes that they will be used by other researchers to produce more effective Parkinson’s medication. “Publishing our results will allow other scientists to use this information to learn more about Parkinson’s, its mechanisms and possible drugs to reduce aggregation. Now one could develop a drug to prevent this interaction so the risk of diabetes will not lead to the risk of Parkinson’s,” says Miller.

Though the research conducted by Miller and her laboratory has yet to be published, it is some of the first to effectively examine the mechanism that causes Parkinson’s disease, a novel endeavor that has won her grants from the European Union Seventh Framework Programme, among other scientific bodies. While it is still unclear what about diabetes, besides the presence of the amylin hormone, triggers a higher risk for Parkinson’s disease, Miller and her team are well on their way to finding out.

Photos: Image Editor/ Dani Machlis, BGU/ Open Knowledge

http://nocamels.com/2014/10/israelis-discover-clear-link-between-diabetes-and-parkinsons-disease/

Sound Waves Can Heal Brain Disorders

Focused ultrasound may help deliver drugs and other treatments

Oct 16, 2014 |By Bret Stetka

RADIO

The brain is protected by formidable defenses. In addition to the skull, the cells that make up the blood-brain barrier keep pathogens and toxic substances from reaching the central nervous system. The protection is a boon, except when we need to deliver drugs to treat illnesses. Now researchers are testing a way to penetrate these bastions: sound waves.

Kullervo Hynynen, a medical physicist at Sunnybrook Research Institute in Toronto, and a team of physicians are trying out a technique that involves giving patients a drug followed by an injection of microscopic gas-filled bubbles. Next patients don a cap that directs sound waves to specific brain locations, an approach called high-intensity focused ultrasound. The waves cause the bubbles to vibrate, temporarily forcing apart the cells of the blood-brain barrier and allowing the medication to infiltrate the brain. Hynynen and his colleagues are currently testing whether they can use the method to deliver chemotherapy to patients with brain tumors. They and other groups are planning similar trials for patients with other brain disorders, including Alzheimer's disease.

Physicians are also considering high-intensity focused ultrasound as an alternative to brain surgery. Patients with movement disorders such as Parkinson's disease and dystonia are increasingly being treated with implanted electrodes, which can interrupt problematic brain activity. A team at the University of Virginia hopes to use focused ultrasound to deliver thermal lesions deep into the brain without having patients go under the knife.

“Using ultrasound to make lesions in the body is not a new concept; however, it's been limited for the brain because of the contours, density and thickness of the skull,” says neurologist and study investigator Binit Shah. The new technique overcomes that hurdle by training more than 1,000 beams onto a target area. Shah and his colleagues' pilot study of patients with essential tremor—a common, usually benign condition of rhythmic shaking—was published in the New England Journal of Medicine last year and found that ultrasonic lesioning of part of the thalamus decreased tremor. The group is expanding the trial and launching other pilot studies to explore several symptoms of Parkinson's.

The benefits of focused ultrasound might extend well beyond restoring mobility and delivering drugs. Other groups are exploring its use in treating neuropathic pain and obsessive-compulsive disorder, too.

This article was originally published with the title "The Sound of Healing."
http://www.scientificamerican.com/article/sound-waves-can-heal-brain-disorders/

The Potential Benefits of Coffee and Cinnamon for PARKINSON’S DISEASE

Two research articles published very recently could make you think that a breakfast of multiple cups of strong coffee and cinnamon rolls was deliciously beneficial for people with PARKINSON’S DISEASE.  The first article is from a team of researchers at Linkoping University in Sweden.  They very carefully looked at the relationship of coffee and a genetic variation specific to PARKINSON’S DISEASE.  The second study came from Rush University Medical Center in Chicago, IL and looked at the potentially beneficial effects of cinnamon as a neuroprotective anti-oxidant for PARKINSON’S DISEASE.  Alas and unfortunately, what makes for good research news is not necessarily good practical advice.

The Swedish coffee research studied 570 subjects from southeastern Sweden, 193 who had PARKINSON’S DISEASE AND 377 controls.  PARKINSON’S DISEASE is thought to result from a complex interaction of genetic predisposition and environmental factors.  While many of the genes involved in PARKINSON’S have been isolated, interactions of individual genes with environmental factors have been much more difficult to study.  This group looked at one single nucleotide polymorphism (SNP), a specific genetic modifier that has been found in many people with PARKINSON’S DISEASE. They genotyped all the subjects to determine if they carried this SNP, then they interviewed them to establish their levels of coffee drinking or caffeine use, either high or low.  They then studied the effects of heavy caffeine consumption or light consumption on this specific SNP and found that heavy caffeine consumption, especially on a particular form of the SNP did provide a protective benefit.

The study of cinnamon from Rush University looked at the benefits of this widely used cooking and baking spice on the brains of mice.  They found that “after oral feeding, ground cinnamon is metabolized into sodium benzoate, which then enters into the brain, stops the loss of Parkin and DJ-1, protects neurons, normalizes neurotransmitter levels, and improves motor functions in mice with PD”  Parkin and DJ-1 are proteins that are known to be compromised by oxidative stress in people with PARKINSON’S.  In this way, sodium benzoate could act as an anti-oxidant, to preserve the cells.  Dr. Kalipada Pahan, the principal investigator of this study enthusiastically states: “Now we need to translate this finding to the clinic and test ground cinnamon in patients with PD.  If these results are replicated in PD patients, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease”

But not so fast, here.  Using anti-oxidants to preserve brain cells is an idea that has shown many good results in mice but has not proved definitively effective in humans.  Cinnamon is just the newest candidate.  More research on the benefit of cinnamon is in order.  Cinnamon breaks down into sodium benzoate in the liver.  Sodium benzoate does not have a great reputation, particularly as an additive to food.  In small quantities, chemically produced sodium benzoate is added to commercial food products as an anti-microbial and a preservative to extend shelf life.  It is also found in pickles, salsas, processed lunchmeats, sodas and juice drinks.  When it combines with acids, such as vitamin C (ascorbic acid) it forms benzene, which is a known carcinogen.  While the sodium benzoate added to food is of a manufactured nature, it is consumed in very small quantities and the Food and Drug Administration does not consider it dangerous although the cumulative effects have not been thoroughly studied.   More research on the safety and effectiveness of cinnamon to protect people from Parkinson’s disease will be informative.

You can still enjoy a cinnamon roll and a good strong cup of coffee…just don’t expect them to deliver the neuroprotection needed to resolve your PARKINSON’S symptoms!

Naomi Yamada-Fowler, Mats Fredrikson, Peter Söderkvist. Caffeine Interaction with Glutamate Receptor Gene GRIN2A: Parkinson’s Disease in Swedish Population. PLoS ONE, 2014; 9 (6): e99294 DOI: 10.1371/journal.pone.0099294

Saurabh Khasnavis, Kalipada Pahan. Cinnamon Treatment Upregulates Neuroprotective Proteins Parkin and DJ-1 and Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease. Journal of Neuroimmune Pharmacology, 2014; DOI: 10.1007/s11481-014-9552-2

Review by Marcia McCall

Comparison of IPX066 with carbidopa-levodopa plus entacapone in advanced PD patients

20th October 2014 - New research

CLINICAL TRIAL RESULTS OF DUAL LAYER L-DOPA

Dual layer L-dopa (IPX066), which is being developed for the treatment of Parkinson's Disease, unusually and advantageously combines the immediate release version of L-dopa with the controlled release version of L-dopa. An application by Impax is with the FDA for the marketing of IPX066 as Rytary.

For more information go to : http://www.drugs.com/nda/rytary_140411.html Rytary

The effect of Dual Layer L-dopa on Parkinson's Disease was compared to the effect of sinemet plus Entacapone, which is one of the most effective forms of L-dopa.

IPX066 demonstrated improved efficacy. The average dosage of L-dopa used in IPX066, after accounting for availability, was 22% higher than in Sinemet and Entacapone.

IPX066 demonstrated less "off" time (3.8 hours instead of 5.2 hours per day). IPX066

demonstrated higher "on" time without dyskinesia (11.4 hours instead of 10 hours per day).

Other measures favoured IPX066. There were more adverse events when taking IPX066. The most common adverse events were dyskinesia, insomnia, and confusional state for IPX066, and falling for Sinemet and Entacapone.

Reference : Parkinsonism Related Disorders [2014] Aug 15 [Epub ahead of print] (F.Stocchi,

A.Hsu, S.Khanna, A.Ellenbogen, A.Mahler, G.Liang, U.Dillmann, R.Rubens, S.Kell, S.

Gupta) Complete abstract : http://www.ncbi.nlm.nih.gov/pubmed/25306200

New research may prove relevant to treating disorders characterized by misfolded proteins - PD, CVD, and cystic fibrosis

Patients with Parkinson's disease, cardiovascular disease, and cystic fibrosis may have something in common: cells in their disease-affected tissues may produce misfolded proteins that are incapable of functioning normally. In the October 16, 2014 online issue of the journal Cell, Stowers Institute scientists report where the misfolded proteins clump together in a cell, and how the cell can prevent the passage of these defective molecules to its daughter cell. Stowers Investigator Rong Li, Ph.D., who headed the study, explains that during cell division, aggregates of these misfolded proteins normally are tethered to the mother cell. As a result, the daughter cell does not inherit the defective proteins that burden the mother cell. By identifying the quality control mechanisms that normally operate in cells, Li and other scientists are providing information that may prove relevant to treating disorders characterized by misfolded proteins.

Using 3-D time-lapse movies to track the fate of misfolded proteins in yeast cells, the researchers determined that about 90 percent of aggregates form on the surface of the endoplasmic reticulum (ER), a location of protein synthesis in the cell. It had been thought that misfolded proteins spontaneously clump together in the cytosol, the fluid component of a cell's interior.

"Our findings have challenged the notion of the aggregation process as a passive consequence of accumulating misfolded proteins," says Stowers Investigator Rong Li, Ph.D., who led the study. Using budding yeast Saccharomyces cerevisae, a frequently used laboratory model in aging research, Stowers scientists experimentally used heat and other forms of stress to induce misfolded proteins to clump together.

Li and collaborators also found that the aggregation of misfolded proteins on the ER surface depends on the active synthesis of proteins by ribosomes. These molecular machines translate the cell's recipes for proteins. Guided by the recipe, the ribosome generates a linear polypeptide chain, the initial form of a protein.

The newly synthesized polypeptide folds into a distinctive three-dimensional structure resulting in a protein with a functional shape. Proteins that fail to fold correctly cannot perform their biological functions and are potentially toxic to cells. Thus, the aggregation of misfolded or unfolded proteins may help protect the cell and prevent their transfer to daughter cells during cell division, said Chuankai Zhou, a predoctoral researcher in the Li lab and first author of the paper.

In addition to determining that protein aggregation is regulated and requires active translation, Stowers scientists revealed that the mitochondria, the cell's powerhouses, play a key role in the mobility of these protein aggregates. "We found the majority of aggregates on the surface of ER were in regions where ER and mitochondria come together, which is surprising but fits well with the view of regulated aggregation," says Zhou.

The current study builds upon previous research, published by the Li lab in 2011 in Cell, that revealed that most aggregates of unfolded proteins are retained by the mother yeast cell during the asymmetric cell division that characterizes this organism as well as stem cells. Budding yeast reproduce when only a small growth out of the mother yeast cell, a bud, becomes a daughter cell.

In the current paper, the scientists identified the quality control mechanism that limits the spreading of the misfolded protein aggregates to the bud and thereby the daughter cell. During the mitosis stage of budding yeast's division, aggregates of abnormal protein are tethered to well-anchored mitochondria in the mother cell. As a result, the mitochondria acquired by the bud are largely free of the abnormal aggregates.

"Remarkably, the majority of aggregates present in the mother cell did not follow the mitochondria that entered the bud, but they either underwent dissolution or remained associated with the mitochondria that were kept in the mother cell and only exhibited confined local mobility," describes Li. "As such, the bud-inherited mitochondria were largely devoid of aggregates."

Disrupting the aggregate-mitochondria association increases the mobility and leakage of mother-accumulated aggregates into the bud. Li and her colleagues also determined that the association of aggregates with mitochondria gradually declines in the mother budding yeast cells with advanced replicative age, likely contributing to their diminished ability to rejuvenate through asymmetric cell division.

The researchers were able to visualize the process because the protein aggregates were labeled with different fluorescently tagged proteins that bind to aggregates. The Electron Microscopy and Imaging core centers at the Stowers Institute assisted with the research.

http://www.medicalnewstoday.com/releases/284083.php

The Parkinson Alliance Reports Findings Pertaining to Autonomic Dysfunction in Parkinson's

PR Newswire

KINGSTON, N.J., Oct. 20, 2014

KINGSTON, N.J., Oct. 20, 2014 /PRNewswire-USNewswire/ -- New findings from The Parkinson Alliance (PA) survey entitled "Autonomic Dysfunction in Parkinson's Disease With and Without Deep Brain Stimulation" show that autonomic dysfunction was highly prevalent in Parkinson's disease (PD), regardless of age and disease duration. The autonomic nervous system controls a number of functions in the body involving the cardiovascular system (i.e., blood pressure, heart rate), digestion, urination, sexual arousal, thermo-regulation (i.e., managing temperature sensitivity), pupillary functions (i.e., light sensitivity), and swallowing. Given that the topic of autonomic dysfunction is less known to people with PD, PA conducted a survey about autonomic dysfunction; 1,489 individuals with Parkinson's participated, including 413 participants who underwent Deep Brain Stimulation (DBS) and 1,076 individuals without DBS. 

Results revealed that older adults and individuals with advanced disease yielded greater reports of autonomic dysfunction. There was a significant relationship between the experience of autonomic dysfunction and emotional well-being, and over half of the participants reported that autonomic disturbance adversely impacts engagement in social activities. As it relates to DBS and Non-DBS groups, there was not a significant difference between these groups for most autonomic symptom domains, with exception to significantly less cardiovascular symptoms and greater difficulties with swallowing for the DBS group when compared to the Non-DBS group.

"This research conducted by The Parkinson Alliance highlights the prevalence of autonomic dysfunction across age and disease duration for individuals with PD, and that autonomic symptoms have both social and psychological implications," said Jeffrey Wertheimer, Ph.D., ABPP-CN, clinical neuropsychologist and Chief Research Consultant for The Parkinson Alliance. Wertheimer added, "Autonomic symptoms are commonly underassessed and undertreated for people with PD. This study has a large number of participants and underscores the importance of people with Parkinson's keeping their doctor/treatment team informed about the experience of autonomic symptoms. Early identification of risk factors, careful diagnosis, and early intervention may have a favorable impact on symptom management and health related quality of life."

Study results can be found on www.dbs4pd.org.

New CGH voice and movement group helps Parkinson's patients using 'big' moves

PUBLISHED ON OCT 10, 2014 1:10 PM 

 

BY KASH CHEONG

SINGAPORE - A new voice and movement group in Changi General Hospital (CGH) is helping Parkinson's patients speak louder and move better.

Started in April this year, four to six Parkinson's patients gather weekly to perform exaggerated actions while attempting to project their voice. Prompted by occupational and speech therapists, patients may sing while extending their bodies sideways or shout their names while stretching their bodies forward.

About 50 patients have gone through this therapy. While most are from CGH's inpatient group, it will be extended to outpatient clients in December. 

The focus is on thinking "big" and "loud" as Parkinson's patients struggle with fine motor movements and a soft voice, said CGH senior speech therapist Betty Wong. Parkinson's patients may also suffer from hand tremors, slow movements, rigidity or be unstable in standing and sitting. Their voices also become softer as the disease progresses.

Parkinson's patient Mrs Yeo Jui Hoon, 84, undergoes a new Voice and Movement Group Therapy with (right) Senior Occupational Therapist Tan Xuan Hong at Changi General Hospital. -- ST PHOTO: SEAH KWANG PENG 

 

- See more at: http://www.straitstimes.com/news/singapore/health/story/new-cgh-voice-and-movement-group-helps-parkinsons-patients-using-big-mov#sthash.NWAaB03x.dpuf