Dance for people living with Parkinson's

December 22, 2017

Dance can support people living with Parkinson's to develop confidence and strength, and provide the opportunity for creativity and self-expression, whist also temporarily relieving some participants of symptoms in everyday life.

"...I've identified about eight or ten words to describe what we’re doing: imagination, creativity, language, colour, music, rhythm. And I’ve not come across anything, anything in my diverse life, which combines all those things. The breadth and depth of what is going on downstairs [in the studio] is significant.”

“I feel released from the Parkinson’s, in more control of my body and with friends.”

Why dance?

There’s an increasing appetite for dance these days and the broad ways it benefits our health and wellbeing. This is felt by people of all ages and physical abilities. One group that now attaches particular value to taking part in dance is that of people living with Parkinson’s.

A growing body of evidence points to the real physical, mental and social benefits experienced by people living with Parkinson’s when they dance. For example, research into English National Ballet’s (ENB) dance and Parkinson’s programme, published in 2015 by Dr Sara Houston of Roehampton University, concluded that dance as a group activity can:

• Encourage feelings of inclusion and positive social interaction
• Promote a sense of community that is particularly meaningful, motivating and energising for people living with Parkinson’s
• Aid fluency of movement
• Help people with Parkinson’s communicate and express themselves.

https://www.communitydance.org.uk/developing-participation/dance-for-parkinsons

Ladbrokes condemned for tweet about darts presenter who has Parkinson’s

December 22, 2017

Darts presenter Dave Clark condemned a Twitter message sent from the Ldbrokes account Sky Sports

The bookmaker Ladbrokes has been condemned for its tweet mocking the Sky Sports presenter Dave Clark, who has Parkinson’s. The broadcaster, who is anchoring Sky Sports’ coverage of the PDC World Darts Championship at Alexandra Palace, was diagnosed with the disease six years ago.

In a now-deleted tweet Ladbrokes uploaded a photo of him and wrote: “Dave Clark looks like he’s caught the whiff of something nasty & wants to murder the person who’s caused it ... #LoveTheDarts.”

Clark responded on Thursday evening with a screen grab of Ladbrokes’ post alongside the message: “That’ll be the chronic degenerative neurological condition that will eventually rob me of the ability to walk, talk and smile @Ladbrokes #parkinsons”.

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The gambling firm’s tweet caused uproar on social media and the former England and Newcastle striker Alan Shearer was among those expressing outrage. The 47-year-old quoted Clark’s tweet and wrote: “Wow! Two people tweeting. One is a gentleman, who inspires us all. The other a little prat on a keyboard hoping for a cheap laugh. I know who I stand with. You’re an inspiration Dave. Keep doing yourself and everyone else proud. #parkinsons #hero”.

Ladbrokes posted an apology on Friday morning for its “completely ill-judged and inappropriate tweet” and vowed to make a donation to the support and research charity Parkinson’s UK. Joanna Wright, the wife of Peter Wright, the No2 seed at Alexandra Palace, promised to donate the shirt and trousers her husband wore in his first-round victory for auction to raise further funds for the charity.

It is not the first time Ladbrokes has been subjected to a social media backlash over a post from its Twitter account. In September the bookmaker apologised to Burnley for “very poorly conceived tweets” sent about the former Leeds players Chris Wood and Charlie Taylor during a Carabao Cup tie between the two clubs.

Ladbrokes, Burnley’s official UK betting partner, had sent a message addressed to Wood and Taylor, followed by an image of a raised middle finger and the words: “Yours sincerely, Leeds fans #LUFC.”

https://www.theguardian.com/sport/2017/dec/22/ladbrokes-tweet-parkinsons-dave-clark-pdc-world-darts

Study explains how exercise can slow Parkinson's disease

By Sam Howard  |  Dec. 22, 2017

Protein accumulations involved in Parkinson's disease are shown in this photomicrograph. Photo courtesy of Suraj Rajan/Wikimedia Commons

Scientists at the University of Colorado Anschutz Medical Campus conducted a study that suggests why exercise can help Parkinson's patients slow the disease's progression.

The critical components are the DJ-1 protective gene and the alpha-synuclein protein, according to a news release announcing the study.

Humans born with a mutated version of the DJ-1 gene get severe symptoms of Parkinson's disease at a younger age than others. Alpha-synuclein molecules bundle together in the brain to help precipitate neurological decline in Parkinson's patients.

In the study from Colorado research associate professor Wenbo Zhou and professor Dr. Curt Freed, mice with Parkinson's were grouped into two categories: those with exercise wheels and those without.

After three months, the mice with wheels managed to increase the DJ-1 gene's expression in the brain and muscles, the scientists found. Those mice also stopped alpha-synuclein molecules from bunching up in the brain.

"Our results indicate that exercise may slow the progression of Parkinson's disease by turning on the protective gene DJ-1 and thereby preventing abnormal protein accumulation in brain," Freed said in the release.

The exercising mice also enjoyed greater cognitive function than those from the immobile group, the release said.

Freed and Wenbo also examined mice that did not have the DJ-1 gene. Based on the decline of activity in those mice, Freed and Wenbo determined the gene may be necessary for a Parkinson's patient to experience normal movement.

The professors' study was published Friday in the journal PLOS ONE.

https://www.upi.com/Health_News/2017/12/22/Study-explains-how-exercise-can-slow-Parkinsons-disease/9641513972326/?utm_source=sec&utm_campaign=sl&utm_medium=1

Researchers propose new term for the role of microbiota in neurodegeneration

December 21, 2017, University of Louisville

Amyloid produced by commensal bacteria may cause changes in protein folding and neuroinflammation in the central nervous system through the autonomic nervous system (particularly the vagus nerve), the trigeminal nerve in the mouth and nasopharynx, and the gut (including mouth, esophagus, stomach and intestines), as well as via the olfactory receptors in the roof of the nose. Credit: University of Louisville

Research in the past two decades has revealed that microbial organisms in the gut influence health and disease in many ways, particularly related to immune function, metabolism and resistance to infection. Recent studies have shown that gut microbes also may cause or worsen Parkinson's disease, Alzheimer's disease and other neurodegenerative conditions.

University of Louisville neurology professor Robert P. Friedland, M.D., and Matthew R. Chapman, Ph.D., professor at the University of Michigan, have proposed a new term to describe an interaction between gut microbiota and the brain in an article released today in PLOS Pathogens.

Friedland and Chapman propose the term "mapranosis" for the process by which amyloid proteins produced by microbes (bacteria, fungi and others) alter the structure of proteins (proteopathy) and enhance inflammation in the nervous system, thereby initiating or augmenting brain disease. The term is derived from Microbiota Associated Protepathy And Neuroinflammation + osis (a process).

Friedland hopes that giving the process a name will facilitate awareness of the process, as well as research leading to therapeutic opportunities.

"It is critical to define the ways in which gut bacteria and other organisms interact with the host to create disease, as there are many ways in which the microbiota may be altered to influence health," Friedland said.

Research into the multitude of microbes that inhabit the human body has expanded considerably in recent years. Genomic analysis has begun to reveal the full diversity of bacteria, viruses, fungi, archaea and parasites living in and on the body, the majority of them in the gut. Even more recently, researchers have begun to explore how the proteins and other metabolites produced by microbes inhabiting the gut influence functions in other parts of the body, including the brain. However, we do not yet have a full understanding of how these systems work. The relationship between the microbiota and the brain has been called the "gut-brain axis."

It is understood that the clumping of misfolded amyloid proteins, structures produced by neurons in the brain, are associated with neurodegeneration and conditions such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS).

"It is well known that patterns of amyloid misfolding of neuronal proteins are involved in age-related brain diseases. Recent studies suggest that similar protein structures produced by gut bacteria, referred to as bacterial amyloid, may be involved in the initiation of neurodegenerative processes in the brain," Friedland said. "Bacterial amyloids are produced by a wide range of microbes that inhabit the GI tract, including the mouth."

In research published in 2016 in Scientific Reports, Friedland and colleagues showed that when E. coli microbes in the gut of rats and worms (nematodes) produced misfolded amyloids, the amyloids produced in the animals' brains and intestines also misfolded, a process called cross-seeding.

"Our work suggests that our commensal microbial partners make functional extracellular amyloid proteins, which interact with host proteins through cross-seeding of amyloid misfolding and trigger neuroinflammation in the brain," Friedland said.

In today's article, Friedland and Chapman also address other factors related to the microbiota and its products and how they influence neurodegenerative disorders.

1. The microbiota modulates (enhances) immune processes throughout the body, including the central nervous system.
2. The microbiota may induce oxidative toxicity (free radicals) and related inflammation that contributes to neurodegeneration.
3. Metabolites produced by the microbiota may be either beneficial (health sustaining) or damaging (pathogenic).
4. Host genetics influence microbiota populations, illustrating that the gut-brain axis is bidirectional.

Friedland believes further research in this area may lead to therapies for these neurodegenerative diseases, which are increasing in frequency and for which there are few effective treatments.

More information: Robert P. Friedland et al, The role of microbial amyloid in neurodegeneration, PLOS Pathogens (2017).  DOI: 10.1371/journal.ppat.1006654 

Journal reference: PLoS Pathogens 

Provided by: University of Louisville 

https://medicalxpress.com/news/2017-12-term-role-microbiota-neurodegeneration.html

FoxFeed Blog: LRRK2 Drug Trial Shares Promising Results, Company to Begin Second Study

Posted by Maggie McGuire Kuhl,  December 21, 2017

Yesterday Denali Therapeutics announced positive results from its first-in-human LRRK2 inhibitor clinical trial. The experimental treatment is safe, and it lowers LRRK2 protein activity in humans' body cells. This is a meaningful milestone in the clinical development of a drug with potential to slow or stop Parkinson's progression (something no currently available treatment can do).

Denali also shared it is testing a second compound in a separate Phase I trial in control volunteers. Following completion of both trials, one of the two compounds will move into studies in people with Parkinson's carrying a LRRK2 mutation.

Read more below on this project and its treatment potential from our earlier report on Denali's initial public offering.

In a press release, the company announced its first trial showed greater than 90 percent inhibition of LRRK2 activity at peak drug levels. This is a critical early step in testing a drug -- does it do what you want it to do in the cell? Denali used two tests to measure inhibition, including one based on a finding from a Michael J. Fox Foundation-organized consortium linking LRRK2 to another protein.

"Mutations in LRRK2 are a major risk factor for Parkinson's disease. Targeting this degenogene represents a promising approach to develop disease-modifying medicines," said Ryan Watts, PhD, Denali CEO.

https://www.michaeljfox.org/foundation/news-detail.php?first-lrrk2-drug-in-clinical-trials-company-files-public-offering

Information on Findings and next steps:  

http://investors.denalitherapeutics.com/news-releases/news-release-details/denali-therapeutics-announces-advancement-and-expansion-its#ir-pages

DENALI THERAPEUTICS ANNOUNCES ADVANCEMENT AND EXPANSION OF ITS LRRK2 INHIBITOR CLINICAL PROGRAM FOR PARKINSON’S 

SOUTH SAN FRANCISCO, Calif., Dec. 20, 2017 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ:DNLI), a biopharmaceutical company developing a broad portfolio of therapeutic candidates for neurodegenerative diseases, today announced that its small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2), DNL201, achieved, on average, greater than 90% inhibition of LRRK2 kinase activity observed at peak and greater than 50% inhibition at trough drug levels at the highest multiple dose tested in a healthy volunteer Phase 1 study. Based on a full review of the clinical data from this ongoing study, and additional preclinical data, the FDA has removed the previously imposed partial clinical hold.

LRRK2 inhibition was measured by two independent blood-based biomarker assays of LRRK2 activity: phosphorylation of LRRK2 at Serine 935 and phosphorylation of the LRRK2 substrate Rab10. Both markers reflect the function of LRRK2 kinase activity and Rab phosphorylation is linked to lysosomal dysfunction associated with Parkinson’s disease. In addition, robust central nervous system penetration of DNL201 has been achieved as demonstrated by measurement of DNL201 in the cerebrospinal fluid (CSF). These data, in combination with pharmacokinetics/pharmacodynamics (PK/PD) modeling, indicate robust and sustained target engagement of LRRK2 in brain.

Denali also announced that it has commenced dosing of its second small molecule inhibitor of LRRK2, DNL151, in healthy volunteers in the Netherlands. Denali now has two distinct small molecules targeting LRRK2 inhibition in human clinical testing for Parkinson’s disease.

Denali plans to select either DNL201 or DNL151 to move into studies in Parkinson’s disease patients carrying a LRRK2 mutation after completion of Phase 1 healthy volunteer studies for both molecules. In the ongoing studies in healthy volunteers, Denali is investigating safety and tolerability, PK and PD in blood and CSF, and characterizing a biomarker to estimate target engagement in brain.

“Mutations in LRRK2 are a major risk factor for Parkinson’s disease. Targeting this degenogene represents a promising approach to develop disease modifying medicines for patients suffering from this terrible disease,” said Ryan Watts, Ph.D., CEO. “By restoring LRRK2 activity to normal levels, we believe we can reverse lysosomal dysfunction, which could potentially benefit both patients with LRRK2 mutations, as well as idiopathic Parkinson’s disease patients who exhibit lysosomal dysfunction,” said Dr. Watts.

“Our robust biomarker assay allows us to establish and monitor LRRK2 target and pathway engagement, and assess the exposures required to reach desired target inhibition. We have demonstrated significant inhibition of LRRK2 kinase activity with DNL201, which gives us confidence to proceed with further clinical testing,” said Carole Ho, M.D., Chief Medical Officer.

About Denali

Denali is a biopharmaceutical company developing a broad portfolio of therapeutic candidates for neurodegenerative diseases. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com.

Cautionary Note Regarding Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements express or implied in this press release include, but are not limited to, plans to progress either DNL201 or DNL151 into studies in Parkinson’s disease patients following completion of Phase 1 healthy volunteer studies for both molecules, results of targeting mutations of LRRK2 to develop disease modifying medicines for Parkinson’s disease patients, the effects of restoring LRRK2 activity to normal levels and potential benefits to both patients with LRRK2 mutations and idiopathic Parkinson’s disease who exhibit lysosomal dysfunction, and Denali’s plans to conduct further clinical testing in this area. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: Denali’s early stages of clinical drug development; Denali’s ability to complete the development and, if approved, commercialization of its product candidates; Denali’s dependence on successful development of its BBB platform technology and product candidates currently in its core program; Denali’s ability to conduct or complete clinical trials on expected timelines; the uncertainty that any of Denali’s product candidates will receive regulatory approval necessary to be commercialized; Denali’s ability to continue to create a pipeline of product candidates or develop commercially successful products; and other risks, including those described in Denali’s Prospectus filed with the SEC on December 8, 2017. The forward-looking statements in this press release are based on information available to Denali as of the date hereof. Denali disclaims any obligation to update any forward-looking statements, except as required by law.

http://investors.denalitherapeutics.com/news-releases/news-release-details/denali-therapeutics-announces-advancement-and-expansion-its#ir-pages

Stay-Safe Strategies for Bad Weather: Heed our expert advice and you won't have to hibernate this winter.

By Kritz, Fran

Neurology Now: December/January 2017 - Volume 13 - Issue 6 - p 15

doi: 10.1097/01.NNN.0000527838.11415.6c

Departments: The Waiting Room

Cold, snowy, icy, or slushy weather can be stressful for anyone with a neurologic condition who worries about falling. Often it's enough to prevent people from venturing out at all. But staying indoors and waiting for spring to come brings its own dangers, says Peter Y. Kim, MD, PhD, associate professor of neurology at the Columbia University Medical Center in New York City. People may become sedentary and isolated, which can affect the progression of their disease or their mental state, Dr. Kim explains.

To stay as safe as possible in poor conditions, consider these tips.

1. SCHEDULE YOUR TIME OUTSIDE CAREFULLY. Run errands and schedule appointments when you feel strongest or when your medication is most effective, says Linda Pituch, a Helpline specialist with the Parkinson's Foundation.

2. WORK WITH AN OCCUPATIONAL OR PHYSICAL THERAPIST. Ask about the best ways to get in and out of a vehicle when there's ice or snow on the ground, or exercises to keep from slipping. Also ask about what assistive devices, such as canes or walkers, are most practical.

3. KEEP EQUIPMENT DRY. Keep a small dry cloth on hand so you or someone with you can wipe off the end of your cane or walker if the tips get wet or snowy, says Dr. Kim.

4. WEAR SUPPORTIVE SHOES. Choose shoes with soles that grip and laces or straps that keep the shoes secure, says Melissa Armstrong, MD, MSC, FAAN, a movement disorders specialist at the University of Florida Health Center for Movement Disorders and Neurorestoration in Gainesville.

5. KEEP HANDS FREE. Ask for help carrying items or wear a backpack. Keeping your hands free will help you balance if you slip or stumble.

6. DON'T MULTITASK. Stay focused on walking and getting to your destination. Don't try to read a map or talk on your cellphone.

7. TRAVEL WITH OTHERS. Bring along a companion. If that's not possible, let others know your route and check in with them when you arrive or if you have problems en route.

8. CLEAR PATHWAYS. Arrange to have a service or a neighbor or relative remove snow and ice as soon as it accumulates. And stay inside if the path outside your door is icy.

9. TAKE PUBLIC TRANSPORTATION. If family or neighbors can't drive you to a doctor's appointment or to run errands, call 311 and ask the operator if your town offers free transportation for older people and those with disabilities.

10. CONSIDER RIDE SERVICES. You can book a ride from Uber (http://uber.com) or Lyft (http://lyft.com) using an app on your smartphone. Rides through LyftLine or UberPool, which match you with someone going in a similar direction, are 20 percent cheaper, and you get the discount even if you're the only passenger.

11. KEEP IMPORTANT PHONE NUMBERS HANDY. Store emergency numbers in your cellphone under ICE (in case of emergency) in the event that someone has to call for you.

http://journals.lww.com/neurologynow/pages/articleviewer.aspx?article=00012&issue=13060&type=FullText&year=2017

10 top tips for the festive season from people with Parkinson’s

Author: Parkinson's UKPublished: 21 December 2017

The festive period can be a busy time, meaning you may find it harder than usual to manage your symptoms. Parkinson’s UK asked people living with Parkinson’s to give their top tips on how to look after yourself and enjoy the season. We share some of their ideas

Doing your Christmas shopping

1. Theresa, who was diagnosed in 2009, suggests:

“If you’re shopping in a busy town or city and you find carrying purchases difficult, it’s worth asking in-store if you can leave items to collect later, or if they offer a delivery service to disabled customers.

2. Josie, who was diagnosed in 2007, advises: “I find a rucksack-style bag much easier to use, as it leaves both hands free while I’m out in public.”

Writing your cards

3. Diane, who was diagnosed in 2012, says: “Use labels in your Christmas cards instead of handwriting them. It makes it so much easier and saves a lot of time too!”

Getting yourself party ready

4. Doreen, whose husband has Parkinson’s, explains: “My husband had problems with ties and we solved it by buying clip-on ones. They are so easy to use: they just attach near the top button on the shirt and are as smart and fashionable as ordinary ties.”

5. Jill, who was diagnosed in 2009, tells us: “Having spent hours trying to fasten a necklace, I finally bought a pack of eight magnetic jewellery clips. If I fix the magnets to each end of my necklaces and it’s so much easier to put them on. The magnets are quite powerful but can’t cope with anything too heavy – so the crown jewels are out!”

Putting on a tie can often be difficult for people with Parkinson’s. Image credit: Parkinson’s UK

6. Diane, who was diagnosed in 2012, advises: “Pace yourself. Christmas Day is likely to be hectic, so don’t do too much in one go. I prepare my Christmas dinner the day before, by chopping the vegetables and cooking the turkey. Take a step back and ask for help if you need it.”

7. Heidi, who was diagnosed in 2014, says: “If you’re going to someone’s house, take anything you need with you. It’s ok that you have Parkinson’s and need support. If you have difficulties in certain areas, such as dexterity, take along your own specialist cutlery to eat with.”

Eating Christmas fayre

8. Diane recommends: “Make sure you watch what you eat and when you eat it. Too much protein can affect your medication. I try to eat my Christmas dinner in the middle of two doses, to avoid the impact. This is easier to manage when you’re hosting and you can set the times of meals.”

Scaling things back

9. Heidi explains: “This year I’m putting myself first and having Christmas dinner with just my husband, rather than seeing a big group of friends and family. Have the strength to say ‘no’ if you’d prefer to do your own thing.”

Making communication easier

10. Kathryn, whose mum was diagnosed with Parkinson’s in 2005, says: “If a member of your family has Parkinson’s and struggles to communicate, make sure they don’t get isolated. Christmas can be a noisy time, so think about turning the TV down a little or just giving the person a bit more time to speak.”

http://parkinsonslife.eu/10-top-tips-festive-season-people-with-parkinsons/