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

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/

Understanding Parkinson's disease

11 hours ago  •  By Amy Fachman/Fremont Health

0

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.

Copyright 2014 Fremont Tribune. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Tags

Fremont Health Medical Center, Parkinson's Disease, Fremont Health

http://health.einnews.com/article/241347397/UpQ32_zDpIJQhrli

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.

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/

How sensor maker ​Qualtré could help both Parkinson's patients and farmers

Dec 23, 2014, 7:24am EST

Qualtré Inc., a Marlborough-based maker of motion sensors, said last week that it raised $9 million in funding from two strategic partners, including Tokyo-based Alps Electric, along with current investors, Matrix Partners and Pilot House Ventures.

Qualtré, which has raised $45 million in total funding, said it would use the new funding to expand its sales and marketing team, scale operations, and extend product development as the company supports new customers and additional applications.

The company specializes in sensors for industrial and high-end consumer applications that are more precise and more affordable than ones from competitors, according to Qualtre CEO Edgar Masri. Masri said Qualtré currently has a dozen beta customers right now who are testing its product. The final product will be released in January, Masri said.

The industrial side of the company focuses on the agriculture industry, for example providing sensors for tractors to help farmers better harvest crops.

Masri said the high-end consumer part of the business would be focused on incorporating the sensors into wearables in the medical and sports fields. In the medical field, for example, Masri said there is "a great need for sensors that can detect Parkinson's patients' tremors, measure them and administer medication accordingly."

In the sports field, the technology could be used to accurately measure the throw of a baseball player. Other applications including incorporating the technology into motorcycles to help adjust headlights depending on the angle of the motorcycle and working it into cameras to help with image stabilization.

Founded in 2008 by CTO Farrokh Ayazi, Qualtré's technology is built on years of research conducted at Georgia Institute of Technology's Integrated MEMS Laboratory, the same school where Ayazi, an author of more than 150 peer-reviewed scientific publications and who holds 12 issued patents, was professor at the Georgia Tech's, School of Electrical and Computer Engineering.

The company currently has 30 employees and has plans to add another 10 workers in the next year, Masri said.

http://www.bizjournals.com/boston/blog/health-care/2014/12/how-sensor-maker-qualtr-could-help-both-parkinsons.html?page=all

Parkinson's: Small molecules researched for the regeneration of dopaminergic neurons

Date:

December 17, 2014

Source:

Helsingin yliopisto (University of Helsinki)

Summary:

Researchers plan to develop orally administrable small molecules that

act similarly to neurotrophic factor GDNF. "GDNF has earlier been 

recognized as a possible eliminator of the cause of Parkinson's disease.

 However, there are problems with the use of GDNF. It diffuses poorly, 

is expensive and does not penetrate blood-brain barrier. So we aim at

 molecules that could work better in this to support suffering neurons

 in the brains of Parkinson's disease patiens," says one expert.

Researchers in the University of Helsinki plan to develop orally administrable small molecules that 

act similarly to neurotrophic factor GDNF

.Parkinson's UK has granted Professor Mart Saarma and postdoctoral researchers

 Yulia Sidorova and Merja Voutilainen from the Institute of Biotechnology, 

Finland, a grant of £35,000 over 8 months to develop orally administrable small 

molecules that act similarly to glial cell line-derived neurotrophic factor (GDNF).

"GDNF has earlier been recognized as a possible eliminator of the cause of

 Parkinson's disease. However, there are problems with the use of GDNF. It 

diffuses poorly, is expensive and does not penetrate blood-brain barrier. So we

 aim at molecules that could work better in this to support suffering neurons in 

the brains of Parkinson's disease patiens," says Professor Mart Saarma.

The group has already identified several candidate molecules which activate

 GDNF receptors in immortalized cells and shown that one of them promoted 

survival of dopamineric neurons in vitro.

"We also have another candidate compound that has not yet been tested on 

dopaminergic neurons. Its ability was better that that of GDNF family member 

artemin to stimulate neurite outgrowth from sensory neurons. We would like to 

test the activity of the the latter molecule towards survival of dopaminergic 

neurons and test both GDNF mimetics in animal model of PD."

---

Story Source:

The above story is based on materials provided by Helsingin yliopisto 

(University of Helsinki). Note: Materials may be edited for content and 

length.

---

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 researched for the regeneration of dopaminergic neurons." ScienceDaily.

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Parkinson's patients identify balance and anxiety treatments among top ten research priorities

Last updated: 20 December 2014 at 12am PST 5 

Patients with Parkinson's, medics and carers have identified the top ten priorities for research into the management of the condition in a study by the University of East Anglia and Parkinson's UK.

Commissioned by Parkinson's UK, people with direct and indirect personal experience of the condition worked together to identify crucial gaps in the existing evidence to address everyday practicalities in the management of the complexities of Parkinson's. Patients stated that the overarching research aspiration was an effective cure for Parkinson's but whilst waiting for this more research was needed into the management of the condition.

Top of the list, which was narrowed down from a list of 94 uncertainties, was the need to identify what treatments help reduce balance problems and falls in people with Parkinson's.

This was followed in second place by questioning what approaches are helpful for reducing stress and anxiety in patients, and what treatments help reduce involuntary movements - a side effect of some medications - in third place.

Also outlined in the top ten research priorities for Parkinson's management, published today on BMJ Open, are better monitoring methods, improving sleep quality and the need to develop interventions specific to the different types of Parkinson's and the dementia that can be associated with Parkinson's.

Dr Katherine Deane, lead researcher from the University of East Anglia, said: "Ensuring that research is effective in addressing the needs of patients and the clinicians treating them is critically important, and the priorities will inform the research plans and funding from Parkinson's UK and hopefully other funders."

"The research agenda has been accused of being overly influenced by the pharmaceutical industry and of not addressing the questions about treatments that are of greatest importance to patients, their carers and clinicians. Research needs to focus on whether treatments are doing more harm than good, or whether one treatment is better than another, and ensure the outcomes reflect issues that have impact on the patient's wellbeing and participation.

"These priorities identify crucial gaps in the existing evidence to address everyday practicalities in the management of the complexities of Parkinson's, with an overarching research aspiration to work towards an effective cure for Parkinson's."

One thousand participants provided initial ideas on research uncertainties, which were narrowed down to 94 unique ideas, which 475 participants used to select their own top ten priority list. A final 26 top priorities were then examined by 27 stakeholders who agreed a final top 10. People with Parkinson's were in the majority in all of these groups.

Arthur Roach, Director of Research and Development at Parkinson's UK, said: "This study highlights the very important fact, sometimes overlooked, that for many people with Parkinson's the most troublesome problems are not the classical motor symptoms, but things like sleep, falls, anxiety and difficulties with thinking. Ensuring that research meets the needs of people with Parkinson's is key and we will be using this awareness to guide our research programme in the future."

The project was led by Parkinson's UK, with the University of East Anglia and the University of Birmingham acting as academic partners. The James Lind Alliance provided an independent chair, advised on the methodology, and facilitated the process.

Overarching research aspiration: An effective cure for Parkinson's

The top ten research priorities for the management of Parkinson's:

• What treatments are helpful for reducing balance problems and falls in people with Parkinson's?
• What approaches are helpful for reducing stress and anxiety in people with Parkinson's?
• What treatments are helpful for reducing dyskinesias (involuntary movements, which are a side effect of some medications) in people with Parkinson's?
• Is it possible to identify different types of Parkinson's, eg, tremor dominant? And can we develop treatments to address these different types?
• What best treats dementia in people with Parkinson's?
• What best treats mild cognitive problems such as memory loss, lack of concentration, indecision and slowed thinking in people with Parkinson's?
• What is the best method of monitoring a person with Parkinson's response to treatments?
• What is helpful for improving the quality of sleep in people with Parkinson's?
• What helps improve the dexterity (fine motor skills or coordination of small muscle movements) of people with Parkinson's so they can do up buttons, use computers, phones, remote controls etc?
• What treatments are helpful in reducing urinary problems (urgency, irritable bladder, incontinence) in people with Parkinson's