Enjoying a worry-free festive season with Parkinson's (UK)

16 December 2016

For many people, overcooking the turkey is the biggest worry they'll face during the holiday season. For people with Parkinson's, however, Christmas time can present some extra challenges.

Plan ahead to make the festive season as enjoyable as possible.

Queues in shops, difficulty parking the car, a constant flow of visitors, and limited medical support can all increase stress and lead to symptoms appearing worse than normal.

So we've put together a few tips on making the holiday season as stress-free and fun as possible.

Keep these things in mind

It's important to plan ahead to make the festive season an enjoyable time. Here are some handy hints to make your Christmas go smoothly:

• Make sure that you have enough medication to last over the holiday period. If you're running low, remember to check the Christmas opening times of your pharmacist/GP.
• Share any extra workload with family and friends.
• Get your shopping done in advance to avoid extra stress and big queues. Online shopping is a good way to avoid the shops at busy times.
• It's important that if you have home care or live in a residential or nursing home that the carers are aware of your plans and needs over the holiday period.

Managing medication

We all over-indulge during the holiday period. Some people with Parkinson's may find that if they take their levodopa-based medication alongside a high protein meal it's not as effective.

Taking your levodopa-based medication half an hour before you eat can often help.

As long as you don't have any other medical issues, alcohol in moderation is generally not a problem.

Accessing medical services

As with any other time of year, people can become ill over the holiday period and there will always be help available if this happens.

If you become ill, your GP surgery will be running an out-of-hours service.

If you need to speak to somebody urgently, please contact:

We wish you a very happy and peaceful break and send our best wishes for the New Year.

• NHS (England) - 111
• NHS Direct (Wales) - 0845 46 47
• NHS 24 (Scotland) - 111
• If you live in Northern Ireland please dial 999 or your out-of-hours GP service.
• Samaritans (UK-wide) - 116 123

Parkinson's UK helpline Christmas hours

Our free helpline 0808 800 0303 will be open at limited times over the holiday period. 

We can be very busy during this time so our main focus will be on dealing with medical enquiries as these are the greatest priority for people with Parkinson's.

Helpline Christmas opening hours:

Friday 23 December: 9am-7pm

Christmas Eve: 10am-1pm

Christmas Day: Closed

Boxing Day: Closed

Tuesday 27 December: Closed

Wednesday 28 December: 10am-2pm

Thursday 29 December: 10am-2pm

Friday 30 December: 10am-2pm

New Year's Eve: 10am-2pm

New Year's Day: Closed

Monday 2 January: Closed

Tuesday 3 January: 9am-7pm

Is someone with Parkinson's visiting you?

If you're entertaining guests with Parkinson's, you might want to read our Diet and Parkinson's booklet to prepare for their Christmas dinner and our Parkinson's Carer's Guide.

We wish you a very happy and peaceful break and send our best wishes for the New Year.

https://www.parkinsons.org.uk/news/16-december-2016/enjoying-worry-free-festive-season-parkinsons

Caring for Someone with Advanced Parkinson’s

As Parkinson’s advances, there is a shift in overall daily caregiving responsibilities. You will face many challenges, but you can ensure best care with thoughtful planning and knowledge. This video provides an overview of what you need to know as the caregiver of someone with advanced Parkinson’s. Watch the rest of the videos in the series, and refer to them as needed, for more information and tips on a variety of caregiving issues.

The information here offers suggestions and helpful hints, but is not designed to answer all questions. Each person with Parkinson’s is unique, so the suggestions may need to be modified for your particular situation. You are strongly recommended to seek and build a team of professionals in your local area to help you on your caregiving journey. If you have questions or need a referral to a local provider, call the National Parkinson Foundation Helpline at 1-800-4PD-INFO (473-4636).

http://caremap.parkinson.org/caring-for-someone-with-advanced-parkinsons/

Plans and Scheduling

When you care for someone with advanced Parkinson’s, you must live life one day at a time, but being organized and planning for many potential outcomes will decrease future stress. These videos will help you keep yourself organized and set up reliable systems to make life a little easier and more enjoyable for both you and your loved one.

Part 1 offers strategies to stay organized and make a routine so that the actions of the person with Parkinson’s can become comfortable habits rather than a daily challenge. Part 2 reviews how to keep medical information organized, prepare for an emergency, plan for the future and, importantly, take time out to enjoy being with the person with Parkinson’s.

The information here offers suggestions and helpful hints, but is not designed to answer all questions. Each person with Parkinson’s is unique, so the suggestions may need to be modified for your particular situation. You are strongly recommended to seek and build a team of professionals in your local area to help you on your caregiving journey. If you have questions or need a referral to a local provider, call the National Parkinson Foundation Helpline at 1-800-4PD-INFO (473-4636).

http://caremap.parkinson.org/plans-and-scheduling/

***Please see Home Care on my blog dated Dec. 14th and Dec. 16, 2016. Good Information.

Care Map Continues

Movement and Falls

As Parkinson’s advances, movement becomes increasingly difficult. You will likely need to provide greater hands-on assistance and learn safe and effective ways to provide help without injuring yourself or your loved one. The videos on this page will give you strategies for helping the person with Parkinson’s move around so that both you and your loved one stay safe. 

Part 1 provides information on how to help the person with Parkinson’s sit down and stand up safely, including tips on cuing and the best furniture options. Part 2 reviews the major changes to mobility – freezing; short, shuffling steps; instability and falls – and their impact on movement and safety for both you and the person with Parkinson’s. This video also reviews how to help someone up from a fall and how to pick the best assistive device for the person with PD.

Tip

To make sure health care providers understand your loved one’s “on” and “off” periods, it can be helpful to show them a video of your loved one’s movements during those times. If you have a recording device, such as a smartphone or digital camera, use it to film your loved one’s “on” and “off” states, then show it to the doctors. This will help them see what “on” and “off” means for your loved one, and may help them adjust treatment and care recommendations.

The information here offers suggestions and helpful hints, but is not designed to answer all questions. Each person with Parkinson’s is unique, so the suggestions may need to be modified for your particular situation. You are strongly recommended to seek and build a team of professionals in your local area to help you on your caregiving journey. If you have questions or need a referral to a local provider, call the National Parkinson Foundation Helpline at 1-800-4PD-INFO (473-4636).

http://caremap.parkinson.org/movement-and-falls/

Activities at Home

Symptoms of advanced Parkinson’s may decrease your loved one’s ability to participate in leisure activities. This video will help you find ways to engage your loved one physically, mentally and socially to maximize his or her mobility and quality of life. 

The information here offers suggestions and helpful hints, but is not designed to answer all questions. Each person with Parkinson’s is unique, so the suggestions may need to be modified for your particular situation. You are strongly recommended to seek and build a team of professionals in your local area to help you on your caregiving journey. If you have questions or need a referral to a local provider, call the National Parkinson Foundation Helpline at 1-800-4PD-INFO (473-4636).

http://caremap.parkinson.org/activities-at-home/

Travel and Transportation

Are you ready to take your loved one with Parkinson’s out of the home for an appointment, family visit or other activity? Traveling can be a cumbersome process with advanced-stage Parkinson’s, but these outings are sometimes needed, and can even be beneficial to your loved one’s well-being. The videos on this page will help you prepare for your journey, whether you are traveling around the corner or around the globe.

Part 1 gives tips to get ready for outings, including making sure your home and car are accessible. Part 2 helps you complete the preparation for your outings with tips for working with a transport company and traveling by plane.

The information here offers suggestions and helpful hints, but is not designed to answer all questions. Each person with Parkinson’s is unique, so the suggestions may need to be modified for your particular situation. You are strongly recommended to seek and build a team of professionals in your local area to help you on your caregiving journey. If you have questions or need a referral to a local provider, call the National Parkinson Foundation Helpline at 1-800-4PD-INFO (473-4636).

http://caremap.parkinson.org/travel-and-transportation/

Mealtime and Swallowing

Your loved one may need your help to get his or her needed nutrition. The videos on this page will review ways to make mealtime safer, less stressful and more enjoyable while helping the person with Parkinson’s maintain independence in eating. 

Part 1 offers tips for meal set-up and examples of foods that are easy to chew and swallow for people with Parkinson’s. Part 2 addresses ways to combat dehydration, weight loss and problems swallowing medications.

The information here offers suggestions and helpful hints, but is not designed to answer all questions. Each person with Parkinson’s is unique, so the suggestions may need to be modified for your particular situation. You are strongly recommended to seek and build a team of professionals in your local area to help you on your caregiving journey. If you have questions or need a referral to a local provider, call the National Parkinson Foundation Helpline at 1-800-4PD-INFO (473-4636).

http://caremap.parkinson.org/mealtime-and-swallowing/

After delay, ISCO's trial of Parkinson's stem cell therapy gets underway again

December 16, 2016    by  Phil Taylor

Analysts predict a phase 2 study could start in late 2017 or early 2018.

A second patient has now been treated in the first trial of a stem cell therapy for Parkinson's disease developed by California biotech International Stem Cell Corporation (ISCO).

The treatment involves transplants of millions of stem cells delivered by intracranial injection in a bid to replace dopamine-producing cells that have died off. In Parkinson's, that neurodegeneration disrupts the neural pathways that govern muscle movements and causes characteristic symptoms such as limb shaking.

So far, the two patients treated to date are showing no ill effects from the therapy, which is being studied in a phase 1 trial involving 12 Parkinson's disease sufferers conducted by researchers at the Royal Melbourne Hospital in Australia.  

It's too early to see if there is any clinical effect of the ISC-hpNSC therapy just now, but there may not be too long to wait—the team will be checking to see if Parkinson's symptoms improve over the course of the 12-month trial and first data could be available in the first quarter of 2017, say analysts at Edison.

"We currently expect that the company will be able to progress to a phase 2 study in late 2017 or 2018 depending on the safety and efficacy profile discovered in the current trial," they said in a research note.

ISCO's trial got underway earlier this year with the first patient receiving the transplant in July, but additional surgical procedures were delayed by "a supply chain disruption of equipment critical to the operation," according to the firm's chief scientific officer Russell Kern. 

The trial is now resuming and will see the doses gradually increased from a level of 30 million cells in the first two patients to a maximum of 70 million cells. 

If safe and effective, stem cell therapy could be a massive step forward for Parkinson's disease patients, who are still treated mainly with the combination of levodopa and carbidopa, which replace the dopamine lost by the death of neurons.

Most of the clinical development of new therapies to date has focused on the reformulation of dopamine-replacing regimens and, to date, no disease-modifying therapies have been approved to help the 7-10 million people worldwide with the disease.

Other companies with cell- and gene-based therapies for Parkinson's in clinical testing include Living Cell Technologies, uniQure, Voyager Therapeutics and Oxford BioMedica.

http://www.fiercebiotech.com/biotech/after-delay-isco-s-trial-parkinson-s-stem-cell-therapy-gets-underway-again

Being in tune is their therapy

 December 15, 2016  By Sophie Hagen

A DUET: Michele Keir and Janet Morrison are co-founders of the newly formed singing group of patients with Parkinson’s.

Rhode Island artist and designer Michele Keir has spent years singing in choruses. After being diagnosed with Parkinson’s disease, she tried running a singing group for others with Parkinson’s: it fell apart for “lack of participation.” “People got sick,” she says. For years, Keir didn’t try to start another one. But when she crossed paths with Mary Akroyd, whose boyfriend has Parkinson’s, at an art workshop for Parkinson’s patients at Kent Hospital, the two discussed how useful a musical group would be to address symptoms and isolation caused by the illness. A new group was born.

Akroyd, Keir says, takes a dynamic approach to the group, explaining basic musical concepts to those who don’t read music and bringing a sense of fun and camaraderie to what is also an effective therapeutic technique. Akroyd, a retired music teacher, has been a church organist, musical director, and composer for 25 years. She uses the educational resources she’s accumulated over the years to develop exercises for the group, emphasizing dynamics in order to coach softer voices to be louder, and “silly children’s songs,” like “Bibbidi Bobbidi Boo” from Cinderella, to help with pronunciation. Uplifting songs like “Climb Every Mountain” remind the participants that they’re not alone in coping with the disease. Choreography, including arm and body movements that mimic the direction of the melody, helps combat the onset of stiffness.

This work provides potentially vital reinforcement for a set of therapies necessary for those with Parkinson’s disease. Those with Parkinson’s perceive sounds to be louder than they are, which often causes them to speak quietly. The Rhode Island branch of the American Parkinson Disease Association particularly advocates that patients undertake LSVT (Lee Silverman Voice Training) therapy, and specifically a program called LOUD. The therapy requires one hour of work a day, four days a week, for four weeks, and can return the patient to “normal loudness,” as long as they continue to do their exercises.

The self-proclaimed “cruise director on the Love Boat of Parkinson’s,” Mary Ellen Thibodeau is information and referral coordinator at Kent Hospital’s Parkinson’s Center. Her work is funded by the APDA and covers Rhode Island and Southeast Massachusetts. She explains that the singing group can help those who have gone through LOUD to practice the techniques they’ve learned. LOUD includes work with swallowing and facial expressions, as Parkinson’s patients have trouble controlling both.

“I imagine,” said Thibodeau, “that singing would help with that too.”

While the Rhode Island APDA does not run the singing group, which has now met twice and has eight members, it has notified its members about it and publicizes it on its website. The chapter, with 2,400 members, runs 17 support groups; a few more are due to start soon. Thibodeau also manages a hotline; during the holidays, she says, that line will be ringing off the hook.

“Usually at this time of year, some well-meaning relative has told [patients] something horrific about Parkinson’s. I reassure them that what they found on the Internet or what Uncle Joe said is not true.”

There are also three Rhode Island providers of Rock Steady Boxing, a national program for Parkinson’s patients, including Fight2Fitness, a boxing gym in Pawtucket run by New England light heavyweight champion Rich Gingras.

 Rhode Island’s Parkinson’s community, Thibodeau said, “is extremely active and extremely knowledgeable; you can go to any support group and the patients are brimming with information.” In addition to providing as much information as possible, the chapter works to provide opportunities for socializing to people with Parkinson’s who, Thibodeau says, tend to self-isolate, “particularly if they have voice issues or face issues.” More than extra practice with their vocal exercises, then, the singing group gives patients the comfort of community – a chance to see that they are not alone.

The group may encourage other development as well. “Creativity,” reports Keir, “gets enhanced with Parkinson’s.” Thibodeau has not seen research to substantiate this, but reports anecdotally that those with Parkinson’s “seem to get more creative,” embarking on visual art and musical projects. “Patients appear to have an increased interest in the arts” once they’ve been diagnosed, she says.

Akroyd, the group’s teacher, says she’s learning as she goes and enjoying the experience thoroughly. The participants have reported a more positive outlook following group meetings. One exclaimed to Akroyd that the singing was “a lot more fun than the loud exercises!”

The group is currently honing its holiday repertoire for a large group sing-along at Kent Hospital on December 17. Its services may soon be in high demand. Evergreen Nursing Home in East Providence has, according to Keir, requested a performance by the group. While the group’s activities focus on those with Parkinson’s, it is open to all.

The group’s next meeting will be held on December 15 from 1 to 3 p.m. at Oaklawn Community Baptist Church (229 Wilbur Avenue, Cranston). Participants should be advised that there are several steps down to the choir room.

http://warwickonline.com/stories/bein-in-tune-is-their-therapy,120467

Is Obama’s ‘Cures Act’ a gamechanger for Parkinson’s treatment?

Author: Parkinson's Life editorsPublished: 15 December 2016

What does the ‘Cures Act’ mean for people with Parkinson’s?

On December 13, President Barack Obama signed the 21st Century Cures Act into US law. Days earlier the Senate had approved the Act with a 94-5 vote, after Parkinson’s campaigners had put pressure on US policymakers to advocate for a national neurological disease data collection system.

The result is the creation of the ‘National Neurological Conditions Surveillance System’ at the Centers for Disease Control and Prevention. This programme will collect demographic information about people living with neurological diseases such as Parkinson’s, to more accurately profile who is living with these conditions.

Allyse Falce, Research Communications Officer of the Michael J Fox Foundation, said: “The database will provide a foundation for understanding many factors, such as clusters of diagnoses in certain geographic regions, variances in the number of men and women diagnosed with neurological diseases, and differences in health care practices among patients.”

The Cures Act also requires the Food and Drugs Administration (FDA) to consider patient perspectives in the drug approval process and start collecting data on patient experience of living with a disease.

Falce said: “Involving patients in this manner will put government regulators in touch with the community’s experiences and priorities as new drugs and devices enter late-stage clinical testing and move toward FDA approval.”

The Bill also puts in place an accelerated review process for breakthrough medical devices that could benefit patients with debilitating chronic conditions.

The 21st Century Cures Act will allocate:

• $1.5 billion over 10 years to the National Institutes of Health (NIH) for the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, which supports specialist development of unique technologies to help researchers improve understanding and treatments for conditions such as Parkinson’s and Alzheimer’s

• $1.5 billion over 10 years to the NIH for the Precision Medicine Initiative, which aims to develop tailored prevention strategies and treatments to each unique individual’s condition. This could be beneficial for people with Parkinson’s whose symptoms vary from person to person.

• $500 million to the Food and Drug Administration to improve access to care, consider patient perspectives in the drug approval process and start collecting data on patient experience of living with a disease.

• $30 million for clinical research to further the field of regenerative medicine using adult stem cells. Stem cell research in the field of Parkinson’s could lead not only to symptomatic therapies but also a deeper understanding of the disease.

http://parkinsonslife.eu/is-obamas-cures-act-a-gamechanger-for-parkinsons-treatment/

Retired Nacogdoches neurologist doesn't let Parkinson's hold her back

Thursday, December 15th 2016 By Donna McCollum

Retired Nacogdoches neurologist Dr. Maria De Leon of Nacogdoches had an ironic twist in life. Her specialty is Parkinson's Disease.

Retired Nacogdoches neurologist Dr. Maria De Leon of Nacogdoches had an ironic twist in life. Her specialty is Parkinson's Disease. A decade ago she was diagnosed with the degenerative disease at the age of 36. Dr. De Leon no longer practices medicine, but as a survivor she continues to guide and mentor Parkinson patients.

De Leon would never be offended if you called her a "diva."

"Everybody in my family thinks I'm a diva and they just, you know, think I just like to bling this and make sure I'm stylish," De Leon said.

De Leon even titled her new book "Parkinson's Diva:A Woman's Guide to Parkinson's."

De Leon prefers the less used definition of diva.

"Being able to do supernatural things with natural abilities," she said. "You know you're limited by what you have, but yet you're able to accomplish so many things."

Accomplishments came early as a young student at the University of Pennsylvania to Queen's Square in London to residency at University of Texas.

"Things worked out and I went to the right medical school," she said. "I went to the right college and became a neurologist and it's ironic I ended up with Parkinson's."

De Leon had to give up her thriving practice, but quickly was determined to reinvent herself.  The doctor became a patient's adviser and advocate for the Parkinson's Disease Foundation.

"It's given me really good insight to be a better doctor, be a better compassionate person and advocate for what's going on because I can see from both sides," she said.

In the forefront is first-hand knowledge that women with Parkinson's Disease have very different symptoms then men. Even as a neurologist, it took two years for De Leon to find out why she was hurting so much.  

"And no one was thinking Parkinson's because of the pain and being so young," she said.

In addition to her book, De Leon blogs about specific topics helpful to anyone with a chronic disease. There's practical information.

"What clothing are good with people that are chronically disabled that are on wheelchairs," she said.

And the more intimate topics.

"This one is Women's Health and Sexuality," she said.

And learning how to listen to the illness.  

"That they're still themselves," she said. "That' they're not any less just because they have a disease."

De Leon considers herself a survivor, best expressed in a poem she wrote titled, "In My Shoes." This remarkable diva reads its final stanza.  

"In my shoes God is always fair and never gives up on me," she said. "His strength in my shoes makes my journey with Parkinson's more than just a bear."

Tears of hope for this survivor who wants to help so many others.

See Video: http://www.kxxv.com//story/34054864/retired-nacogdoches-neurologist-doesnt-let-parkinsons-hold-her-back#.WFMRV9PAlMY.email

http://www.kxxv.com/story/34054864/retired-nacogdoches-neurologist-doesnt-let-parkinsons-hold-her-back

Alzheimer's: Proteomics gives clues toward alternatives to amyloid

December 15, 2016

Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

In Alzheimer's research, one particular protein looms large: plaque-forming amyloid-beta. Yet doctors now recognize that plaques can accumulate decades before symptoms appear. Recent clinical trials aimed at controlling or removing amyloid-beta have largely been disappointing.

Proteomics—analyzing in an "unbiased" way how all the proteins in the brain accumulate or disappear—could provide clues to alternative mechanisms and even treatment strategies, scientists think.

Researchers at Emory University School of Medicine have performed the first large-scale analysis of post-mortem brain proteins in Alzheimer's, using systems biology tools previously reserved for gene expression data.

Comparing samples from Alzheimer's patients with those from healthy elderly controls and patients with other neurodegenerative diseases, the team identified networks of changing proteins that were specific to Alzheimer's. Putting together protein and gene data, the scientists saw patterns pointing to the importance of inflammation and certain cell types, such as microglia, the brain's scavenger immune cells, which gobble up amyloid plaques.

The results are scheduled for publication in Cell Systems on Dec. 15.

"Our findings make a significant contribution towards understanding the earliest molecular changes at the protein level in human brain, which are linked to Alzheimer's pathogenesis and cognitive decline," says co-lead author Nicholas Seyfried, PhD, assistant professor of biochemistry and neurology at Emory University School of Medicine and director of the Emory Integrated Proteomics Core.

This paper is the first proteomics study emerging from the Accelerating Medicines Partnership for Alzheimer's Disease, a $92 million collaboration between the National Institutes of Health and major pharmaceutical companies.

"The purpose of this project is to employ large-scale unbiased discovery approaches using postmortem human brains to identify changes in protein networks that are most closely linked to cognition and the hallmark neuropathology, especially those changes that occur in the earliest, preclinical stages of disease," says Allan Levey, MD, PhD, chair of neurology at Emory University School of Medicine and director of Emory's Alzheimer's Disease Research Center.

Emory investigators collaborated with the Baltimore Longitudinal Study of Aging, (BLSA), which provided brain tissue from people diagnosed with Alzheimer's disease (AD) and healthy elderly controls, as well as those defined as having "asymptomatic AD"; that is, people with normal cognition, but who at death had pathological signs of AD, including amyloid-beta plaques. By looking at this unique set of brains, researchers could tease out protein signatures involved in preclinical versus symptomatic disease states.

"It's been known for some time that many older people have amyloid buildup without having symptoms of Alzheimer's," Levey says. "This group is particularly important, because this is includes people in the preclinical stages of the disease who likely have developed symptoms if they had lived longer, and thus represents the first stages of disease progression. However, it could also include people who have a cognitive reserve, or have some biological mechanisms of resilience against the negative effects of amyloid."

For almost all of the BLSA cases, comprising 97 individual samples, two regions of the brain's cortex were examined. In addition, the team validated their findings by comparing them against 32 samples from the Emory ADRC brain bank, which included healthy controls and those with AD, Parkinson's disease and ALS (amyotrophic lateral sclerosis). This allowed the team to identify early protein changes in the preclinical stage of AD, as well as those that were AD-specific.

The investigators also compared their findings with previously published data on gene expression (RNA, which shows how genes are turned on and off) in Alzheimer's. While the gene activity data were reflected in the protein modules, most modules altered in Alzheimer's proteins were not seen in the gene data. These included modules associated with microtubule function, RNA/DNA binding, and inflammation.

Some of the "protein-only" modules were enriched with blood proteins that were likely deposited in the brain following breakdown of the blood-brain barrier, the authors write. They also speculate that discrepancies between RNA and protein networks could come from a spatial mismatch between cell bodies (where the genes are) and degenerating axons where proteins are supposed to be produced.

By mapping known genetic risk factors for late onset AD onto both the protein and RNA networks, the scientists saw patterns pointing to the importance of microglia and oligodendrocytes, cells of the brain that produce insulating myelin sheaths around neuronal axons. In contrast, similar analyses using genetic risk factors for autism spectrum disorder and schizophrenia emphasized neuronal rather than glial biology.

"At the systems level, we see a convergence in both the transcriptome and proteome on networks associated with inflammation and glial cells, further highlighting the importance of non-neuronal drivers in Alzheimer's pathogenesis," Seyfried says.

The researchers are now seeking to move their findings into the clinic. Some of the signature proteins seen in AD brain have been previously detected in blood plasma or CSF (cerebrospinal fluid), and could serve as excellent candidate biomarkers, Seyfried says. Measuring these markers in patients' blood or CSF could provide the basis for tests that would help doctors diagnose or even predict AD before the onset of symptoms.

In addition, the proteomics data generated by the Emory team is being used to validate and prioritize new targets and mechanisms in the Accelerating Medicines Partnership consortium. The Emory team is expanding the project to include thousands of new study participants, using more advanced mass spectrometry techniques.

Journal reference: Cell Systems

Provided by: Emory University

http://medicalxpress.com/news/2016-12-alzheimer-proteomics-clues-alternatives-amyloid.html

Timing may be key to understanding cognitive problems in Parkinson's disease

December 15, 2016

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

When a cheetah chases a gazelle, it's not raw speed that predicts the outcome of the contest. Instead, it's the animal that times its movements better that has the advantage. That ability to consciously guide movements over a timeframe of a few seconds is a simple but universal thinking skill in mammals. It also is an ability that is consistently impaired in patients with Parkinson's disease (PD), and for University of Iowa neurologist Nandakumar Narayanan that makes "timing" an ideal tool to study cognitive problems in PD.

Parkinson's disease is caused by loss of the brain signaling chemical dopamineand affects about 1 million people in the United States. It is most commonly thought of as a disease that causes movement problems, but neurologists now know that PD can significantly affect patients' thinking, or cognitive abilities, too.

"The cognitive problems associated with PD are very debilitating," says Narayanan, MD, PhD, UI assistant professor of neurology. "They affect quality of life by causing loss of the ability to work, nursing home placement, falls, and increased health care costs. We have a lot of great treatments for the motor symptoms of Parkinson's disease, but there is very little I can do to treat the cognitive symptoms, and that is very frustrating for me."

Working in the lab and the clinic, Narayanan and his team record brain activityin mice and humans as they do simple timing tasks. The scientists also use various genetic technologies to manipulate and study brain activity in the mice. These experiments help to reveal the neurocircuitry that controls timing ability, and explain how this simple cognitive process is disrupted by a lack of dopamine.

In a new study, published online Dec. 15 in the journal Current Biology, the researchers show for the first time that brain stimulation of specific neurons at a specific frequency can improve timing in mice that are missing dopamine. The findings imply that, at least in theory, it might be possible to use brain stimulation to improve cognitive problems caused by PD, and possibly other cognitive disorders, too.

The team studied 12 patients with PD and showed that their ability to judge a period of time (12 seconds) was much poorer than people without PD. Measurements of brain activity from the frontal cortex using EEG (electroencephalography) showed that PD patients were also missing a specific brain wave known as the delta wave, which cycles at a frequency of about 1-4 times per second (1-4 Hertz), while they were doing the timing task.

As expected, mice that lacked dopamine in their frontal cortex also performed poorly on a timing task. However, the team was excited to discover that the animals were also missing the delta rhythm, suggesting that this specific, dopamine-dependent neural signal might be important for timing abilities.

In the frontal cortex, dopamine normally activates neurons with D1 dopamine receptors. The UI team, including Young-Cho Kim, PhD, first author on the study and a postdoctoral fellow in Narayanan's lab, genetically altered the mice so that the D1 neurons could be artificially activated using pulses of light. When the researchers pulsed the light at the same frequency as the missing delta wave signal—2 Hertz—the mice recovered their ability to perform the timing task.

"This was jaw-dropping," Narayanan says. "For the first time we are able to deliver brain stimulation to improve a cognitive behavior.

"When we stimulated D1 neurons in normal mice, we did not improve their timing'" he adds. "But in mice that have cognitive (timing) impairment due to loss of dopamine, we can make those mice better. The results suggest that, theoretically, delivering targeted, selective, and specific brain stimulation might improve some of the cognitive aspects of losing dopamine in Parkinson's disease."

Brain stimulation is already used to treat some patients with PD, but the therapy targets specific areas of the brain that are important for motor control (not the frontal cortex) and only improves movement problems of PD. The new findings suggest precise stimulation of specific neural networks in the cortex might also form the basis of new therapies that improve cognitive processes that depend on dopamine.

More information: Current Biology, DOI: 10.1016/j.cub.2016.11.029

Journal reference: Current Biology

Provided by: University of Iowa 

http://medicalxpress.com/news/2016-12-key-cognitive-problems-parkinson-disease.html

Re­search­ers cor­rect Par­kin­son's mo­tor symp­toms in mice

December 15, 2016

A research group led by University of Helsinki Docent Timo Myohanen has succeeded in correcting the motor symptoms associated with Parkinson's disease in mice. Credit: Ville Korhonen

Up to two per cent of people over 60 contract Parkinson's. The disease causes severe motor symptoms, as it destroys the nerve cells in the brain's motor areas. The exact cause of the disease is not known, but during the past 15 years research has focused on a protein called alpha-synuclein, which has several functions in the brain areas that regulate motor functions.

This protein is prone to mis-folded forms, which can clump together as aggregates. In Parkinson's disease, aggregated alpha-synuclein proteins accumulate within nerve cells, damaging them. They can also propagate from one cell to the next and spread the impairment of nerve cells in the brain.

Researchers had previously known that the PREP enzyme, which occurs naturally in the body, can increase the formation of such harmful alpha-synuclein aggregates in the brain. Now researchers wanted to determine the connection that the enzyme and protein have to the symptoms of Parkinson's disease by blocking PREP in the brain.

In the study, Myöhänen's group set up a mouse model for Parkinson's disease, in which the brain's motor areas were made to produce large amounts of alpha-synuclein. This led to the accumulation of mis-folded proteins in the brains of the mice as expected, resulting in the associated motor symptoms.

PREP blockers restore motor skills

The researchers began treatment with a PREP blocker only when the mice began manifesting clear motor symptoms. The situation would be similar in a human case of Parkinson's which is typically diagnosed only once the symptoms have appeared. Researchers were astounded by the rapid results.

"After as little as two weeks of treatment, the motor symptoms in the mice had practically disappeared. And they did not reappear until after the experiment was over," explains Myöhänen.

A detailed analysis established that the PREP blocker treatment had stopped the motor areas from becoming further damaged and had cleared the brain of nearly all accumulations of alpha-synuclein.

"We have a long way to go from animal models to human trials, but these results are extremely encouraging in terms of future drug development," says Myöhänen.

The results of Myöhänen's group have been published in the internationally esteemed Journal of Neuroscience.

More information: R. Svarcbahs et al. Inhibition of Prolyl Oligopeptidase Restores Spontaneous Motor Behavior in the -Synuclein Virus Vector-Based Parkinson's Disease Mouse Model by Decreasing -Synuclein Oligomeric Species in Mouse Brain, Journal of Neuroscience (2016). DOI: 10.1523/JNEUROSCI.2309-16.2016 

Journal reference: Journal of Neuroscience

Provided by: University of Helsinki 

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