Smart shoes with lasers make strides in mobility

• 17 December 2014 by Aviva Rutkin

THE right shoes can do more than complement your outfit. A new mobility aid named Path helps people who have trouble walking – simply by being fitted to their shoes.

Lise Pape, an engineer at InnovationRCA at the Royal College of Art in London, was inspired to build the system by her father, who was diagnosed with Parkinson's disease more than 10 years ago. Like many people with Parkinson's, he falls occasionally and experiences freezing of gait, the temporary impression that his feet are glued to the ground.

Visual cues have been shown to improve the pace and extend the stride of people with Parkinson's. So a laser that Path adds to the tip of the shoe projects parallel lines onto the next 50 centimetres of the floor. Each shoe lays down a guide for the opposite foot, keeping the grid steady until the wearer is ready to take the next step.

In addition, pressure sensors inserted into the soles of the shoes trigger vibrations when a foot hits the ground. This active feedback is designed to compensate for loss of sensation in the feet, another common symptom of Parkinson's. The soles and the toe projectors can easily be fitted to an ordinary pair of shoes.

Earlier this year, Pape tested Path on one person with Parkinson's and two with multiple sclerosis, another disease that impairs movement. The preliminary results were presented on 10 December at the Footwear Health Tech Conference in Eindhoven, the Netherlands. "I've had a lot of encouraging feedback from patients," Pape says. She plans to run a clinical trial early next year and wants to explore how the shoes can help people with spinal cord injuries.

"It's a great idea," says Peter Schmidt of the National Parkinson Foundation in Miami, Florida. He says projected lines are a great aid, but up until now they've only been built into canes and walkers.

This article appeared in print under the headline "Smart shoes with lasers make strides in mobility"

http://www.newscientist.com/article/mg22430002.800-smart-shoes-with-lasers-make-strides-in-mobility.html?cmpid=RSS%7CNSNS%7C2012-GLOBAL%7Cmagcontents#.VJGulLgALg

Meth users face substantially higher risk for getting Parkinson's disease

 news on december 16, 2014 - 5:30pm

(SALT LAKE CITY)--In addition to incurring serious dental problems, memory loss and other physical and mental issues, methamphetamine users are three times more at risk for getting Parkinson's disease than non-illicit drug users, new research from the University of Utah and Intermountain Healthcare shows. 

The researchers also observed that women who use methamphetamine may be nearly five times more likely to get Parkinson's disease compared to women who don't use drugs. Although findings suggest the risk in women may be higher than that in men, additional studies are needed to corroborate a gender difference. 

"Typically, fewer females use meth than males do," says Glen R. Hanson, D.D.S., Ph.D., a nationally recognized expert in drug addiction, professor and interim dean of the University of Utah School of Dentistry and professor of pharmacology and toxicology, the study's senior author. "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."

Published Dec. 11, 2014, in Drug and Alcohol Dependence, the study looked at more than 40,000 records in the Utah Population Database (UPDB), a unique compilation of genealogical, medical, and government-provided information on Utah families that is managed by the Huntsman Cancer Institute at the University of Utah. Karen Curtin, Ph.D., research assistant professor of medicine at the University and associate director of the UPDB, is the study's first author. Records from University of Utah Health Care and Intermountain Healthcare also provided unidentified patient data that was essential for getting a statewide perspective on the research.

The study confirms an earlier one that looked at nearly 250,000 California hospital discharge records and found a similar risk for Parkinson's among meth users. That study, however, did not report risks based on gender and looked only at records of hospital inpatients. Hanson and Curtin's study included both Utah inpatient and outpatient clinic records, capturing a wider segment of the population.

Parkinson's disease is a progressive movement disorder, with onset typically at age 60 or older, that affects nerve cells in the brain. Its symptoms include tremor, or shaking, often starting in a hand or fingers; slowed movement, such as walking; rigid muscles; loss of automatic movements-blinking or smiling, for example-and speech changes. There is no cure for Parkinson's, but medications and surgery can alleviate symptoms. It is estimated that 4 million to 6 million people worldwide have the condition. 

Hanson, Curtin and their colleagues examined medical records, dating from 1996 through 2011, separated into three groups: those of nearly 5,000 people whose health records indicated they had used meth (including amphetamines), more than 1,800 records indicating cocaine use, and records of a control group of more than 34,000 people selected at random whose health and other records showed no use of illicit drugs. The control group was matched to the meth and cocaine users according to age and sex. The researchers made sure that the group of meth users did not have a medical history of taking other illicit drugs or abusing alcohol, which might have influenced the risk for Parkinson's. 

Cocaine users, who provided a non-meth illicit drug comparison, were not at increased risk for Parkinson's. "We feel comfortable that it's just the meth causing the risk for Parkinson's, and not other drugs or a combination of meth and other drugs," Hanson says. 

All identifying information was removed from the records, so people counted in the study remained anonymous. 

The reason female meth users are more at risk for Parkinson's is not clear. Symptoms of the disease appeared in both female and male meth users in their 50s or later, indicating that the effects of meth may manifest years after initial use. "Oftentimes, we think about what drugs do in the short term, but we don't tend to give much thought to long-term consequences," Hanson says. 

Meth has become in some ways the drug of choice in the West, where it's used more commonly than in other parts of the country. In Utah, the trend toward meth use is particularly pronounced in women their late 20s and older who start taking the drug because of pressure from a partner or spouse.

"Female users in Utah may also get involved with meth because it's seen as a relatively cheap and effective way to lose weight and have more energy," Curtin says. Previous studies show that when women begin using drugs, they take smaller amounts than men, but escalate more rapidly to addiction and are at greater risk for relapse. "Normally, women develop Parkinson's less often than men; however, women may not achieve the same improvement in symptoms from medications or surgery. "If meth addiction leads to sharply increased incidence of Parkinson's disease in women, we should all be concerned."

Source: University of Utah Health Sciences

Identifying early signs of cognitive decline which are already present in some individuals during midlife

Signs of cognitive decline related to aging populations, and even the severe cognitive losses seen in Alzheimer's disease and neurodegenerative disorders, may emerge many years earlier, according to a report presented at the American College of Neuropsychopharmacology annual meeting in Phoenix (Arizona). The study suggests that early signs of cognitive decline are already present for some individuals during midlife, and that they are linked with risk factors such as elevated blood pressure. It is possible that if these risk factors are identified and modified early on, it will be possible to help detect and prevent the progression of cognitive deficits later in life.

As the population in developed countries ages, dementia and other conditions related to significant cognitive decline, and neurodegenerative disorders, such as Alzheimer's disease and Parkinsonism are becoming the major causes of disability in the elderly, and are a major public health concern. Although many of these conditions take decades to develop, a key step to prevent the downward spiral of cognitive decline is to identify risk factors earlier in life, so that they can be targeted and modified.

Studying a cohort of 3,499 biracial adults (the Coronary Artery Risk Development in Young Adults Study (CARDIA), who were followed since early adulthood (ages 18-30 years) through midlife (ages 43-55 years), Kristine Yaffe and colleagues at the University of California San Francisco examined the role of chronic exposure to cardiovascular risk factors (e.g. high blood pressure and fasting glucose levels) and lifestyle behaviors (e.g. diet, exercise) as predictors of cognitive decline during midlife. They found that the cumulative exposure to some of these risk factors, including clinical subthreshold (that is, within the normal range), but elevated, blood pressure, and low physical activity over the 25 years of the study was associated with worse cognitive performance in midlife, based on tests such as the Stroop Interference Score, the Digit Symbol Substitution Test and the Rey Auditory Verbal learning Test.

What is unique about these findings is that they provide evidence that changes in cognition can be detected during midlife (or even in young adults), and that they are associated with cumulative exposure to modifiable risk factors. Thus, these findings suggest that prevention strategies should target these risk factors to stop or reduce the progression of cognitive decline as early as possible.

These studies represent a critical step in the identification of antecedents of diseases of aging, in this case, cognitive impairment and neurodegenerative disorders, many years before they are diagnosed. The understanding that processes of cumulative risk for cognitive diseases of aging start early in adulthood provides a real opportunity for early identification and the use of prevention interventions for those at risk. Dr. Yaffe plans to continue imaging this CARDIA cohort for another 5+ years, to examine predictors of cognitive decline and correlations with brain findings.

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/286889.php

Consider Restless Genital Syndrome in Parkinson's

the Neurology Advisor take:

Parkinson’s disease (PD) is rarely associated with discomfort in the genital region; however, researchers suggest that restless genital syndrome should be a part of the differential diagnosis in PD patients, according to a study published in JAMA Neurology. 

Restless genital syndrome, sometimes also referred to as persistent genital arousal disorder (PGAD), causes feelings of pain, discomfort, tingling and burning sensations in the genital region and can be disabling and very distressing to patients. 

A woman aged 65 years with PD complaining of severe and persistent discomfort in the genital region. Symptoms occurred at night and were often triggered by sitting or lying down for periods of time. During examination, no gynecological abnormalities were observed. She was treated with a low dose of a dopamine agonist and reported improvement.

Although the disorder is rare, researchers suggest that restless genital syndrome be included in the differential diagnosis of genital symptoms and restlessness, as well as nonmotor wearing off and akathisia. Treatment with dopamine agonists can improve symptoms. 

In PD, Restless Genital Syndrome Should Be Considered

In this case study, Camila C. Aquino, MD, MSc, of the Morton and Gloria Shulman Movement Disorders Center at Toronto Western Hospital in Ontario, Canada, and colleagues observed a female Parkinson's disease patient complaining of severe and disabling symptoms in the genital region, including burning sensations, tingling and pain. Previous rare cases were attributed to nonmotor off symptoms.

While restless genital syndrome is rare, researchers suggest that it be included in the differential diagnosis of genital symptoms and restlessness, and recommend treatment with a dopamine agonist. 

http://www.neurologyadvisor.com/restless-genital-syndrome-in-parkinsons-disease/article/376826/

Biotech Entrepreneur Tony Coles Takes Aim At Parkinson's And Alzheimer's

Tony Coles, the chief executive who sold Onyx Pharmaceuticals to Amgen  for $10.4 billion in 2013, is starting a new company that will use yeast to try and discover new treatments for Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease.)

The new startup, Yumanity, will be based in Cambridge, Mass., and is built around technologies developed by Susan Lindquist, the former director of the MIT-affiliated Whitehead Institute for Biomedical Research. Three researchers who worked in Lindquist’s lab will serve as founding scientists for the company, which currently has five employees. Coles says he hopes to scale up to 25.

“I love a big problem and a good challenge and I think that this challenge is sized about right,” Coles says. “We’ve got 50 million people around the world suffering from these diseases, $650 billion in economic costs, and lots of families like mine that have been affected.”

Three specific technologies were created at the Lindquist lab that may allow drug researchers to search more effectively for drugs against neurodegenerative diseases. In all of these disorders, proteins that play important roles in the brain become mis-folded – they are literally misshapen. (Lindquist won the National Medal of Science for her work in how proteins fold in the brain.)

When these misfolded proteins are put into yeast cells, they die. The first step taken using the Yumanity technology is to find drug compounds that keep the yeast cells from dying. These are then put into human neurons derived from induced pluripotent stem cells created from people who have the neurodegenerative disease being studied.

If the drug seems effective in human cells, it is then put back into yeast to try and figure out what molecular target it affects. By this back-and-forth approach (yeast, then human, then yeast, then human again) it should be possible to find and understand new drugs for the disease.

The approach was honed in a trio of Science publications (one, two, three) over the past three years. Even working in an academic lab, Lindquist’s researchers have been able to screen 500,000 compounds against each of three diseases (Parkinson’s, Alzheimer’s, ALS). A bigger effort will be possible at a company, especially as drug companies may be willing to share their proprietary compound libraries as part of the process.

Coles and Lindquist met as members of the board of directors at a previous company she started, FoldRx, which was sold to Pfizer PFE +0.26%. She called Coles to ask him if he would be interested in commercializing her new work. “I couldn’t have imagined anyone who I would rather work with on this than Tony,” she says.

Despite the fact that the work is far more research-based than what he had previously done—Yumanity is a research-stage company, whereas Onyx didn’t invent compounds but bought and developed cancer drugs others had discovered – Coles took the job. He also brought on Kenneth Rhodes, a former Biogen Idec executive, to serve as Chief Scientific Officer.

Yumanity is initially being funded by the founders (Coles received more than $57 million from the Onyx deal) but a funding round is expected to close early next year. Coles says that there is also interest in large pharmaceutical firms who might partner with Yumanity.

Yumanity is still in the very early stages of research. None of its work is ready to be tested in humans. It does have one lead in Parkinson’s, and the company is conducting some research in animal models, not just in cell lines. But the potential is big. Coles says: “I think we’ve got a way to transform the way new drugs are identified and potentially the way new drugs can be discovered.”

http://health.einnews.com/article/239840679/1G1S_NrxwrBIQcEB

Parkinson's disease affects youngsters too, says body

Published on: Tuesday, December 16, 2014 KUALA LUMPUR: Contrary to common belief that Parkinson's disease (PD)  attacks only the elderly, young people are also at risk, says Malaysian  Parkinson's Disease Association  (MPDA) president Sara Lew.  She said in Malaysia, the disease could affect anyone, regardless of age and  gender, including those in their 20's and 30s, and that men suffered more than  women.  "However, one per cent of individuals over 60 years of age and three per cent  older than 80 have PD," she said at a news conference after announcing a  collaboration between Quest Group of Companies and the MPDA to raise up  to RM30,000 for the association here Monday.  Lew said based on unofficial statistics, the progressive disease had affected  about 50,000 people in Malaysia and the number was growing.  She said the most common symptoms of PD included uncontrolled tremors  in the hands or feet, stiffness of the limbs, slowness of movement and  difficulty with balance.  "The problem may become worse if left untreated or incorrectly treated.  Therefore, it is important to be diagnosed carefully by a neurologist to  ensure that it is Parkinson's," added Lew, whose father had PD for 21 years  before he passed away, four years ago. –  Bernama http://health.einnews.com/article/239847260/h8FuhQDA9dt69oFe

Living Cell Technologies : LCT completes patient implants in Parkinson's trial

Microsoft Word - 141215 141204 Fourth patient implanted Living Cell Technologies Limited ACN: 104 028 042 ASX: LCT OTCQX: LVCLYASX ANNOUNCEMENT

LCT completes patient implants in Parkinson's trial

15 December 2014 - Sydney, Australia & Auckland, New Zealand - Living Cell Technologies Limited today announced that the final patient has been successfully implanted in its Phase I/IIa clinical trial of regenerative cell therapy NTCELL® for Parkinson's disease. The operation took place at Auckland City Hospital last week.

The Phase I/IIa clinical trial, led by Dr Barry Snow, is an open-label investigation of the safety and clinical effects of NTCELL in patients who no longer respond to current therapy. Dr Snow MBChB, FRACP, FRCPC, leads the Auckland Movement Disorders Clinic at the Auckland District Health Board and is an internationally recognised clinician and researcher in Parkinson's disease.

LCT anticipates presenting the results of the 26-week trial at the 19th International Congress of

Parkinson's Disease and Movement Disorders in San Diego in June 2015.

Dr Ken Taylor, chief executive, notes that the success of the implant procedure means that LCT's clinical programme remains on track.

"The treatment phase of the trial has been completed on schedule. We believe NTCELL has the potential to be the first disease-modifying treatment for patients who are failing the current conventional treatment for Parkinson's disease," said Dr Taylor.

- Ends - For further information: www.lctglobal.com At the company:

Ken Taylor

Chief Executive

Tel: +64 9 276 2690

Mobile: +64 21 796000 ktaylor@lctglobal.com

Media enquires:

Rachael Joel

Botica Butler Raudon Partners

Tel: +64 9 303 3862

Mobile: +64 21 403 504 rachaelj@botica.co.nz

About Living Cell Technologies

Living Cell Technologies (LCT) is an Australasian biotechnology company researching and developing cell therapies to treat diseases with high unmet clinical need. LCT's lead product NTCELL® is an

alginate coated capsule containing clusters of neonatal porcine choroid plexus cells. After transplantation NTCELL functions as a biological factory producing factors to promote new central nervous system growth and repair disease induced nerve degeneration.

NTCELL is in Phase I/IIa clinical trial in New Zealand for the treatment of Parkinson's disease. It has the potential to be used in a number of other central nervous system indications such as Huntington's, Alzheimer's and motor neurone diseases.

LCT's proprietary encapsulation technology, IMMUPEL™, allows cell therapies to be used without the need for co-treatment with drugs that suppress the immune system.

LCT holds a 50% interest in Diatranz Otsuka Limited which is developing a cell therapy for type 1 diabetes.

LCT is listed on the Australian (ASX: LCT) and US (OTCQX: LVCLY) stock exchanges. The company is incorporated in Australia, with its operations based in New Zealand.

For more information visit www.lctglobal.com or follow @lctglobal on Twitter

LCT disclaimer

This document contains certain forward-looking statements, relating to LCT's business, which can be identified by the use of forward-looking terminology such as "promising," "plans," "anticipated," "will," "project," "believe," "forecast," "expected," "estimated," "targeting," "aiming," "set to," "potential", "seeking to," "goal," "could "provide," "intends," "is being developed," "could be," "on track," or
similar expressions, or by express or implied discussions regarding potential filings or marketing approvals, or potential future sales of product candidates. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no assurance that any existing or future regulatory filings will satisfy the FDA's and other health authorities' requirements regarding any one or more product candidates nor can there be any assurance that such product candidates will be approved by any health authorities for sale in any market or that they will reach any particular level of sales. In particular, management's expectations regarding the approval and commercialization of the product candidates could be affected by, among other things, unexpected clinical trial results, including additional analysis of existing clinical data, and new clinical data; unexpected regulatory actions or delays, or government regulation generally; our ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures; and additional factors that involve significant risks and uncertainties about our products, product candidates, financial results and business prospects. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results
may vary materially from those described herein as anticipated, believed, estimated or expected. LCT is providing this information and does not assume any obligation to update any forward-looking statements contained in this document as a result of new information, future events or developments
or otherwise.

Study Detects Parkinson’s Symptoms Years Before Diagnosis

- Dec 09 2014

A new study based on the medical records of more than 8,000 people with Parkinson’s disease (PD) from the United Kingdom reports that, compared with healthy individuals, people with PD were more likely to experience symptoms such as tremor and constipation as many as ten years before their diagnosis. The results appear in the November 27 online edition of The Lancet Neurology. 

Doctors diagnose PD based on movement symptoms. But by the time difficulties such as tremor or rigidity become troublesome, more than half of the brain’s dopamine neurons that help control movement, may be lost. Much research is devoted to discovering therapies to slow or stop this brain cell death, and such neuroprotective therapies are most likely to be effective if given as early as possible.  

Knowing that symptoms like depression can appear before movement difficulties develop, researchers led by Anette Schrag, M.D., at University College London, looked for early PD symptoms in the medical records of more than 50,000 people in the United Kingdom. They identified 8,166 individuals diagnosed with PD at age 50 or more, between 1996 and 2012, and analyzed the symptoms recorded by their primary care physicians beginning ten years before the PD diagnosis. The researchers then compared the records with those of 46,755 healthy individuals of similar age and background. 

Results

• Ten years before a diagnosis of Parkinson’s, the incidence of tremor and constipation was more than double in those who went on to develop PD than in those who did not.
• Five years before diagnosis, people who later would develop PD, complained of more tremor, balance problems, constipation, low blood pressure, erectile dysfunction, urinary problems, dizziness, fatigue, depression and anxiety than those who did not develop PD.
• Two years before diagnosis, these people also had more rigidity and memory problems than those who did not develop PD.

What Does It Mean?

This study is the largest ever to chart the first occurrence of a large number of PD symptoms, prior to diagnosis, in a consistent group of people over time. The results support the current scientific understanding that PD affects movement, the digestive system, and other bodily functions well before a diagnosis is made by a neurologist.   

The major limitation of the study is that the participants were not necessarily examined by a neurologist when they first reported tremor, gait difficulty or change in memory, so it is unclear whether diagnosis could have been made earlier. Also, participants were not examined by the researchers conducting this study, so PD diagnosis is based on their medical records only. It is also important to note that while those who complained of nonmotor symptoms — constipation, low blood pressure, erectile dysfunction, urinary problems, dizziness, fatigue, depression and anxiety — were more likely to develop PD than those who did not complain, most of those who complained did not develop PD. 

However, this study and others can eventually lead to a way of screening for a wide range of symptoms, to identify those at risk for PD earlier on. Also, the results could eventually help scientists looking to develop neuroprotective therapies, which need to be tested in early-stage PD. With a better understanding of how common the early symptoms of PD are, researchers may be able to identify clinicaltrial participants at risk for PD who may be more likely to benefit from neuroprotective treatments. But first, more research is needed.  This study was not able to combine the frequencies of several symptoms together to help develop a reliable tool to predict early PD.

Commenting on the study, Anthony E. Lang, M.D., of the University of Toronto, points out that Parkinson’s remains notoriously difficult to diagnose. There is no definitive blood test, scan or other “biomarker,” and indeed, some people included in this study may have had an incorrect diagnosis. Ultimately, the study makes a valuable contribution to understanding early PD symptoms, while underscoring the need for reliable means of diagnosing the disease.

Reference: Schrag A, Horsfall L, Walters K, Noyce A, Petersen I (2014) Prediagnostic Presentations of Parkinson’s Disease in Primary Care: A Case-Control Study. The Lancet Neurology DOI: 10.1016/S1474-4422(14)70287-X

Published online November 27, 2014 

The full text is available for free at: http://dx.doi.org/10.1016/S1474-4422(14)70287-X

Parkinson's patients identify balance, anxiety among top 10 research priorities

Date:

December 15, 2014

Source

University of East Anglia

Summary:

Patients with Parkinson's, medics and carers have identified the top ten priorities for research into the management of the condition. People with personal experience of the condition worked together to identify crucial gaps in the existing evidence to address everyday practicalities in managing Parkinson's. 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.

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:

1. What treatments are helpful for reducing balance problems and falls in people with Parkinson's? 

2. What approaches are helpful for reducing stress and anxiety in people with Parkinson's? 

3. What treatments are helpful for reducing dyskinesias (involuntary movements, which are a side effect of some medications) in people with Parkinson's? 

4. Is it possible to identify different types of Parkinson's, eg, tremor dominant? And can we develop treatments to address these different types? 

5. What best treats dementia in people with Parkinson's? 

6. What best treats mild cognitive problems such as memory loss, lack of concentration, indecision and slowed thinking in people with Parkinson's? 

7. What is the best method of monitoring a person with Parkinson's response to treatments? 

8. What is helpful for improving the quality of sleep in people with Parkinson's? 

9. 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? 

10. What treatments are helpful in reducing urinary problems (urgency, irritable bladder, incontinence) in people with Parkinson's?

---

Story Source:

The above story is based on materials provided by University of East Anglia. Note: Materials may be edited for content and length.

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Journal Reference:

1. K. H. O. Deane, H. Flaherty, D. J. Daley, R. Pascoe, B. Penhale, C. E. Clarke, C. Sackley, S. Storey. Priority setting partnership to identify the top 10 research priorities for the management of Parkinson's disease. BMJ Open, 2014; 4 (12): e006434 DOI: 10.1136/bmjopen-2014-006434

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University of East Anglia. "Parkinson's patients identify balance, anxiety among top 10 research priorities." ScienceDaily. ScienceDaily, 15 December 2014. <www.sciencedaily.com/releases/2014/12/141215094318.htm>.

Yeast are first cells known to cure themselves of prions

Yeast cells can sometimes reverse the protein misfolding and clumping associated with diseases such as Alzheimer's, according to new research from the University of Arizona.

When colonies of baker's yeast cells that contain clumped prion proteins (colonies of white cells on left) are stressed by high temperatures, some can convert the aggregated prion proteins to the non-clumping form of the protein (red cells in the colonies the right).
Credit: Serio laboratory/ University of Arizona molecular and cellular biology

The new finding contradicts the idea that once prion proteins have changed into the shape that aggregates, the change is irreversible.

"It's believed that when these aggregates arise that cells cannot get rid of them," said Tricia Serio, UA professor and head of the department of molecular and cellular biology. "We've shown that's not the case. Cells can clear themselves of these aggregates."

Prions are proteins that change into a shape that triggers their neighbors to change, also. In that new form, the proteins cluster. The aggregates, called amyloids, are associated with diseases including Alzheimer's, Huntington's and Parkinson's.

"The prion protein is kind of like Dr. Jekyll and Mr. Hyde," said Serio, senior author of the paper published in the open-access journal eLife. "When you get Hyde, all the prion protein that gets made after that is folded in that bad way."

For yeast, having clumps of amyloid is not fatal. Serio and her students exposed amyloid-containing cells of baker's yeast to 104 F (40 C), a temperature that would be a high fever in a human. When exposed to that environment, the cells activated a stress response that changed the clumping proteins back to the no-clumping shape.

The finding suggests artificially inducing stress responses may one day help develop treatments for diseases associated with misfolded prion proteins, Serio said.

"People are trying to develop therapeutics that will artificially induce stress responses," she said. "Our work serves as a proof of principal that it's a fruitful path to follow." 

These yeast cells contain a prion protein that can change shape from a non-clumping form to one that aggregates into clumps called amyloids. Proteins in these cells have the non-clumping shape and are tagged with a marker that fluoresces green under UV light.
Credit: Serio laboratory/ University of Arizona molecular and cellular biology

First author on the paper "Spatial quality control bypasses cell-based limitations on proteostasis to promote prion curing" is Serio's former graduate student Courtney Klaips, now at the Max Planck Institute for Biochemistry in Munich. The other authors are Serio's students Megan Hochstrasser, now at the University of California, Berkeley, and Christine Langlois of Brown University. 

National Institute of Health grants R01 GM069802001, F31 AG034754 and F31 GM099383 funded the research.

To accomplish their jobs inside cells, proteins must fold into specific shapes. Cells have quality-control mechanisms that usually keep proteins from misfolding. However, under some environmental stresses, those mechanisms break down and proteins do misfold, sometimes forming amyloids.

Cells respond to environmental stress by making specific proteins, known as heat-shock proteins, which are known to help prevent protein misfolding.

Serio and her students wanted to know whether particular heat-shock proteins could make amyloids revert to the normal shape. To that end, the team studied yeast cells that seemed unable to clear themselves of the amyloid form of the prion protein Sup35.

The researchers were testing one heat-shock protein at a time in an attempt to figure out which particular proteins were needed to clear the amyloids. However, the results weren't making sense, she said.

So she and Klaips decided to stress yeast cells by exposing them to a range of elevated temperatures - as much as 104 F (40 C) - and let the cells do what comes naturally.

As a result, the cells made a battery of heat-shock proteins. The researchers found at one specific stage of the cell's reproductive cycle, the yeast could turn aggregates of Sup35 back into the non-clumping form of the protein.

Yeast cells reproduce by budding. The mother cell partitions off a bit of itself into a much smaller daughter cell, which separates and then grows up. 

The fluorescent green chunks in these yeast cells are prion proteins that have assumed the shape that aggregates into clumps called amyloids. The prion proteins in these cells are tagged with a marker that fluoresces green under UV light.
Credit: Serio laboratory/ University of Arizona molecular and cellular biology

The researchers found in the heat-stressed yeast, just when the daughter was being formed, the mother cell retained most of the heat-shock proteins called chaperones, especially Hsp-104. As a result, the mother had a particularly high concentration of Hsp-104 because little of the protein was shared with the daughter.

The mother cells ended up "curing" themselves of the Sup35 amyloid, although the daughters did not. The degree of curing was correlated with the concentration of Hsp-104 in the cell, and the higher the temperature the more Hsp-104 the cells had.

The Hsp-104 takes the protein in the amyloid and refolds it, Serio said. But she and her colleagues found that just inducing high levels of Hsp-104 in cells by itself does not change the amyloid protein back to the non-clumping form.

"Clearly the heat-shock proteins are collaborating in some way that we don't understand," she said.

Having the amyloid-forming version of the protein is not automatically bad, she said. It may be that shape is good under some environmental conditions, whereas the non-aggregating form is good under others.

Even in humans, amyloid forms of a protein can be helpful, she said. Amyloid proteins are associated with skin pigmentation and with hormone storage.

To clear the amyloid from yeast cells, these experiments triggered cells to make many different heat-shock proteins.

Serio now wants to figure out the minimal system necessary to clear amyloids from a cell. Knowing that may help the development of drug therapies for amyloid-related human diseases, she said. 

Adapted by MNT 

http://www.medicalnewstoday.com/releases/286781.php