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Welcome to Our Parkinson's Place


I copy news articles pertaining to research, news and information for Parkinson's disease, Dementia, the Brain, Depression and Parkinson's with Dystonia. I also post about Fundraising for Parkinson's disease and events. I try to be up-to-date as possible. I have Parkinson's
diseases as well and thought it would be nice to have a place where
updated news is in one place. That is why I began this blog.
I am not responsible for it's contents, I am just a copier of information searched on the computer. Please understand the copies are just that, copies and at times, I am unable to enlarge the wording or keep it uniformed as I wish. This is for you to read and to always keep an open mind.
Please discuss this with your doctor, should you have any questions, or concerns. Never do anything without talking to your doctor. I do not make any money from this website. I volunteer my time to help all of us to be informed. Please no advertisers. This is a free site for all.
Thank you.


Thursday, September 21, 2017

High fat diet displays health benefits in mice

 By AVERY GULINO on September 21, 2017

The study can be applied to human health as mice age similarly to humans.


The Bacon Diet. Believe it or not, there is an actual diet colloquially known as the Bacon Diet, and it may just stave off illness, help you lose weight, help you become stronger, give you more energy and help you live longer.
This eating plan does not consist of only bacon but rather many different high-fat foods with very limited carbs. This drives your body into what is known as ketosis, where the body shifts from using glucose as its main fuel source to burning fat to generate ketones for energy.
Ketogenic diets have been used for almost a hundred years — clinically, for the most part, since the 1920s to treat epilepsy, especially in kids. They have only grown in popularity in the past few years when people began to notice its amazing health benefits: everything from improving symptoms of Alzheimer’s and Parkinson’s disease and protecting the brain in cases of stroke and injury, to improving cardiovascular health and reducing the risk of cancer. 
Most recently, however, studies at the University of California, Davis have found that the ketogenic diet can also help you live longer and retain a better quality of life. 
In this study, a research team observed mice eating very specific diets with varying amounts of fats and carbs over the course of their entire lives, measuring their mental and physical abilities along the way.
The researchers separated mice into three different groups: the control group, which got 65 percent of their daily calories from fat, a low-carb group that ate 70 percent of their calories from fat and a ketogenic group that got 89 percent of daily calories from fat. 
The calorie counts among these diets were kept the same to ensure caloric intake was not a factor in the study. 
The reason for that was while restricted calories have been proven to slow the process of aging in mice, the main focus of this study was to determine if the proportions of macronutrients in a limited calorie diet would have any effect. 
According to ScienceDaily, Jon Ramsey, the senior author of the paper, was surprised by the results they found. 
“We expected some differences, but I was impressed by the magnitude I observed — a 13 percent increase in median life span for the mice on a high-fat vs. high-carb diet,” he said. “In humans, that would be seven to 10 years. But equally important, those mice retained quality of health in later life.” 
The research team tested the mice in the study in a series of tests at 13 months and then again at 26 months to see how the effects of time and the diet changed not only their physical strength but also their mental acuity. 
To test memory, the mice were put through a novel object recognition test. The mice on the ketogenic diet performed better than those on the low-carb and control diet.
To test their physical abilities, the mice had their grip strength evaluated by hanging on wires and by going through speed and rearing tests. In every evaluation, however, the mice on ketogenic diets showed that they retained greater physical fitness later in life. 
One of the most promising inadvertent results of the study was the mice on the ketogenic diet had fewer tumors in their body upon death. 
The link between ketogenic diets and cancer treatments has been somewhat established, and further clinical trials are being called upon to explore the correlation between the two. The ketogenic diet is hypothesized to affect cancer cells through glucose ‘starvation.’ This denies energy molecules to tumor cells which then inhibits their cell division rates.
Because the aging process in humans and mice is not that different at the molecular level, there is hope that the results of increased life span, mental acuity and physical ability will translate to human life as well. 
“In this case, many of the things we’re looking at aren’t much different from humans,” Ramsey said to ScienceDaily. “At a fundamental level, humans follow similar changes and experience a decrease in overall function of organs during aging.” 
Overall, this study indicates that there are multiple positive effects of this ketogenic “bacon” diet, ranging from cancer research to Alzheimer’s and even longevity.

http://www.jhunewsletter.com/2017/09/21/high-fat-diet-displays-health-benefits-in-mice/

Parkinson Association of Alabama boosting statewide footprint

September 21, 2017  

Mary T. Miller


The Parkinson Association of Alabama is launching some key initiatives that could have nationwide impact down the road.

Birmingham’s PAA, which formed its first junior board this week, has partnered with the American Parkinson’s Disease Association to create a resource center that will be a centralized one-stop shop for residents with Parkinson’s as well as their families.

The APDA is contributing initial startup funding of $40,000 over the next year for the initiative, which aims to launch in January, but PAA Executive Director Mary T. Miller said the nonprofit will begin a long-term fundraising campaign to both keep the center going and to establish a greater presence in Birmingham.

“The PAA will be seeking significant funding to develop and maintain the resource center and care navigator position for the next two years,” Miller said. “The amount needed to start the center and the position will exceed $250,000 for the first years.”

PAA currently does not have an office space in Birmingham, and the nonprofit runs a lean budget with employees working from home. The same concept will continue with the resource center and its care navigator.

“We will start off with a care navigator that we will hire by the end of the year,” 

Miller said. “This person will work from home in the beginning, as he/she will be going around Birmingham and the state telling neurologists and others about the PAA and the new center. As it grows, we hope to have office space that will house the coordinator and possibly the executive director as well.”


https://www.bizjournals.com/birmingham/news/2017/09/21/parkinson-association-of-alabama-boosting.html

Stem cell therapy for your health: 4 things you need to know

September 21, 2017     Vernise L. Tantuco

Stem cells can prevent diseases like Parkinson's and Alzheimer's – here's how they work

STEM CELL THERAPY. Doctor Mary Jan Torres stands by the machine that The Zen Institute uses to separate stem cells from fat and blood. Photo by Alecs Ongcal/Rappler

MANILA, Philippines – Stem cell therapy may not be what first comes to mind when the topic of health and wellness is brought up, but it's an option that has made the rounds abroad and is now here in the Philippines.
The treatment, also called regenerative cell therapy (RCT), uses stem cells to restore damaged or weaker cells and tissues – it's often used to treat joints or cancer, through a bone marrow transplant.
But RCT for wellness is a preventive measure, rather than a cure – it's a way of improving the "quality of life," said doctor Mary Jane Torres, owner and medical director of The Zen Institute, a medical spa that offers the treatment for an introductory price of P25,000.
"Stem cells are usually decreased when you age. It cannot cope with the wear and tear of your body," Torres explained, on why people usually get RCT. By extracting your own stem cells and re-injecting them into your body, they're activated once again, initiating cell growth.
But how exactly are stem cells used as an anti-aging treatment? Here are all our questions answered by Dr. Torres. 
How does RCT for wellness work?
When you undergo stem cell therapy for wellness, your own stem cells are collected and injected intravenously back into your body. The treatment is supposed to work the same way as localized RCT – what's used to treat swelling in the knee, for example – but for your entire body, by boosting your immune system and preventing degenerative diseases like Parkinson's and Alzheimer's.
What's the procedure?
At The Zen Institute, stem cells are taken either from your blood or from your fat. Blood is drawn as you would for a blood test, while fat is removed from the abdomen using a needle. Not a lot of fat is needed – 200 cc – but some patients opt to undergo liposuction along with RCT, since their fat is already being removed.
OPERATING ROOM. RCT is a non-invasive procedure, but it's done at The Zen Institute's sterile clinic, rather than one of the spa's other rooms. Photo by Alecs Ongcal/Rappler
The fat or blood goes into a machine to separate the stem cells, which are then injected intravenously to the patient within the same day.
Patients can do the procedure awake and it takes about 4 hours.

Who can get the procedure?

Torres recommends RCT for people over 30 who are not sick but have a family history of cancer or degenerative diseases. Cancer patients in remission can do it as well, or people with controlled diabetes or hypertension. She reiterated that RCT is not a cure – it's a means of prevention.
How do you know it's working and long will the effects last?
According to Torres, the effects of RCT will last for 5 years, though The Zen Institute also gives their patients a "booster" after a few years to make sure their stem cells are at a certain level.
To check if the treatment is effective, The Zen Institute measures the free radicals in their patients' blood before and after the procedure. "Usually there's a dramatic drop in the oxidative stress test," said Torres on the results.
Torres herself had the treatment done two years ago, and said that she did feel an increase in energy, and noticed an increase in metabolism, both of which spurred on her exercise and activities, making her slimmer. Torres also has health reasons for undergoing RCT – her father died of cancer at 60 years old, and her mom was diagnosed with Parkinson's Disease at 65.
Would you consider getting stem cell treatment for your health? Let us know what you think of it in the comments below! – Rappler.com
https://www.rappler.com/life-and-style/wellness/182839-stem-cell-therapy-wellness-rct

Living a good life with YOPD

September 21, 2017

Natasha McCarthy with her husband Aaron and daughters Samantha and Izabelle, as Natasha’s Ninja’s at Parkinson SuperWalk 2016.


Four years ago at the age of 36, Natasha McCarthy of PEI was surprisingly relieved to find out she had young onset Parkinson’s disease (YOPD). It took 15 months for her doctor and specialist in New Brunswick to make the diagnosis. At the time, she was working fulltime, her daughters were five- and two- years- old and her husband was working in Alberta, with extended visits home to the island.
“I actually thanked my specialist for telling me I was not crazy, when he confirmed my diagnosis,” says McCarthy. “The long and stressful process has you doubting yourself,” she adds. McCarthy also had a grandmother and two aunts with multiple sclerosis, so that possibility was first ruled out. Although her diagnosis wasn’t confirmed until September of 2013, she began taking levodopa in March of that year and it helped with her symptoms.
Blair Sigurdson in Winnipeg had his Parkinson’s diagnosis confirmed six years ago, just before his fiftieth birthday. “But, I think I’d had it for at least 13 years by then,” he says. Sigurdson didn’t experience tremors, but more slowness and rigidity in the years before his diagnosis. At one point he took an extended leave from work, and underwent strengthening therapy that enabled him to return to work. “But once I was back at work, and no longer in the gym so much, my symptoms returned.”
Like McCarthy, Sigurdson had a young family when he was formally diagnosed: a 10-year-old daughter and an eight-year-old son. YOPD presents unique challenges since most people are in the midst of raising families and pursuing careers. YOPD is an unexpected and unwelcome intruder into their busy lives, affecting not only the individual, but the daily lives of the entire family.
McCarthy explains her approach to the unique challenges of YOPD this way: “You and Parkinson’s are going to be together for a very long time. It’s going to be a long, hard road, if you decide to lie down and give up. It’s best to take charge and concentrate on what you can do, not what you can’t.”
Both Sigurdson and McCarthy are proponents of physical activity as part of their self-care. McCarthy horseback rides, and recently completed a five-day, 273 km. cycling event across PEI in support of Parkinson Canada. “It was the hardest thing I have ever done physically, and a lot more emotional that I ever thought it would be. I cried a lot. Not just from the exhaustion of cycling in both heat and torrential rain, but from what I was feeling and the support we received.”  The event raised almost $7,000 and garnered plenty of media attention and public awareness.
Sigurdson has also climbed a few mountains – literally. In the last few years, he has tackled trails rising more than 14,000 feet in the mountains of Colorado, with another fellow living with Parkinson’s. “When I was diagnosed, my doctor told me to take my medication and not exert myself. These days we know that physical activity can help alleviate symptoms, so I push myself because it works for me.”
While these two have completed some exceptional feats, they encourage others with YOPD to simply pursue an activity they love and focus on the positive aspects of their lives. They also recommend seeking out a support network beyond family and friends and venture into the Parkinson’s community. “No one knows better than someone with Parkinson’s what you are going through,” says McCarthy.
Blair and Natasha were discouraged when they attended their first support group meetings. Everyone was much older, with more noticeable symptoms. “It was actually terrifying at first to see your future in the flesh,” says McCarthy. Since then, they both came to appreciate the groups and to see their value. And now, both are involved with Parkinson Canada support groups especially for people with YOPD.
In the Maritimes, a group of about 25 people with YOPD or newly diagnosed with PD, meets monthly via videoconference and in Winnipeg the YOPD support group of about 35 members meets in person each month. “Even members who don’t come out often, tell me they feel better just knowing it is there,” says Sigurdson, who is the group facilitator.
He sets up guest speakers for most meetings, often health professionals such as a speech language pathologist, a neurologist and a physiotherapist, to help people live their best life with YOPD. There is also time to share and ask questions of one another. “It helps to know you are not alone,” he says. He also keeps the group informed about other Parkinson Canada resources, like webinars and educational events, that they might find helpful.
McCarthy says the PEI chapter of Parkinson Canada works hard to provide support for people in the area living with Parkinson’s. In addition to a monthly support group meeting, they provide three activity classes each week, including movement, boxing and singing.
Natasha has also been active as a Parkinson Ambassador, meeting with MPs about genetic fairness legislation, which recently passed in the House of Commons. In addition, she was an official blogger for the World Parkinson Congress 2016 in Portland, Oregon. She attended the Congress and was surprised when other participants wanted to have their picture taken with her. “You’re the girl with the blog,” they’d say. Today her blog has almost 140,000 readers and she gets plenty of emails. Natasha finds writing the blog is therapeutic and brings her comfort.
Blair Sigurdson (front row, far right), Marc Pittet, Blair’s daughter Jenna, his wife Karren and his son Tyler at Parkinson SuperWalk in Winnipeg, earlier this month.
Both Blair and Natasha still face challenges. Natasha admits that giving up work was harder than learning her diagnosis. And when both her daughters boarded the school bus last fall, she felt she could no longer claim to be a stay-at-home Mom. “I felt I’d lost my identity when I had to stop working and then again, I was depressed when both my daughters were at school.” She saw a therapist to help her establish a new routine and get past the crisis. Anxiety and depression are common symptoms of Parkinson’s.
Blair also decided to stop working two years ago. “It got to the point where I could barely function at work and couldn’t do anything with the family. I was in really bad shape.” Now, he drives the kids to school and their activities, exercises, rests, and does his best to avoid stress. “Stress really affects people living with Parkinson’s,” says Blair. “And no amount of medication seems to work when you are stressed.” And both Sigurdson and McCarthy experience sleep difficulties.
This past weekend, both Natasha and Blair took part in Parkinson SuperWalk in their communities in support of Parkinson Canada. They credit their connections to Parkinson Canada with enriching their lives, providing support, education and information and a wide network of friends who understand life with Parkinson’s.
If you or someone you know has YOPD, or is newly diagnosed with Parkinson’s disease, be sure to visit Parkinson.ca for more information. In particular, check out our Young Onset Parkinson’s Disease – Advice for Those Newly Diagnosed, (2nd edition). This booklet was developed from a Parkinson Canada funded research project led by Dr. Mike Ravenek, contains advice directly from individuals currently living with YOPD.  There is also a version for health care professionals.
http://parkinsonpost.com/living-a-good-life-with-yopd/

Using electrical activity in the brain to overcome freezing

September 21, 2017

Assistant Professor Caroline Paquette


Although most of us take it for granted, turning while we walk is a complicated job. Our brains must calculate where to place our feet, and how to adjust and maintain our balance when we shift direction – all in a split second.
For some people with Parkinson’s disease, turning often results in freezing. Without warning, they find themselves rooted in place. They cannot simply will themselves to move forward.
At McGill University, Caroline Paquette, an assistant professor in the Department of Kinesiology and Physical Education, is trying to determine what regions of the brain are affected in people with Parkinson’s disease who experience freezing. She’s using Positron Emission Tomography (PET) to scan the brains of people with Parkinson’s after they have walked through a series of obstacles that require turns. Her research is being funded by a two-year, $90,000 New Investigator Award from the Parkinson Canada Research Program.
“We know that turning is complex walking, and it’s a huge trigger for freezing,” Paquette says. “It’s quite a big problem in people with Parkinson’s disease, because if your mobility is affected, it affects your quality of life and independence.”
To discover how to overcome freezing, Paquette must first understand what mechanisms in the brain are involved. Before the people in her study begin walking, Paquette and her team inject them with a small radioactive tracer. After they have completed their walking and turning task, technicians scan their brains to see what areas the tracer has lit up, indicating increased activity.
By studying those brain scans of people with Parkinson’s who freeze while walking, as well as the scans of people with Parkinson’s who are not affected by freezing, and comparing those images to scans from people without Parkinson’s disease, Paquette hopes to identify the specific areas of the brain that turning activates.
Paquette will then use another non-invasive technology, called Transcranial Magnetic Stimulation, to stimulate those areas of the brain that seem under-utilized in people who are experiencing freezing.
Coupling TMS, which involves using magnets to create electrical activity in the brain, with current rehabilitation regimes might reduce or eliminate freezing, Paquette believes.
Rehabilitation is already somewhat effective in reducing incidents of freezing, Paquette noted.
“With training, we know that you can get people to have fewer debilitating freezing events, to use other cues on their own and to rely less on the environment. If you are able to use Transcranial Magnetic Stimulation on top of that you could get results faster and maybe have longer-lasting effects,” Paquette says.
If Paquette can prove her theory, her research would open up new areas of treatment and reduce the isolation, anxiety and fear of falling that plague those people with Parkinson’s disease who never know when they will find themselves stuck and unable to move.
For Paquette, this Parkinson Canada grant comes at a critical time because the study will help launch her reputation and her research.
“This is the key for me to build the basis for my lab and my research program so we can get funding to make better treatment interventions available for people with Parkinson’s disease, to improve their mobility.” Paquette says.
Read about other researchers recently funded by the Parkinson Canada Research Program by visiting the research section of www.parkinson.ca.

http://parkinsonpost.com/using-electrical-activity-in-the-brain-to-overcome-freezing/

You should be dancing!

September 21, 2017


Take a cue from the Bee Gees’ hit song and consider taking a dance class especially designed for people living with Parkinson’s disease (PD). No need to mimic John Travolta in Saturday Night Fever, these dance classes are modified to be safe and effective for their participants with PD, as well as their spouses or care partners, while offering the joy of dance and all the benefits of moving to music.
AB (Alice Betty) Rustin has been taking a Sharing Dance for People with Parkinson’s class at Canada’s National Ballet School for three years now and a Dancing with Parkinson’s class in the city as well. “It’s always great to spend time with others with Parkinson’s,” says AB. “And I feel better after a class. The movements are not as strenuous as in an exercise class. They are much more fluid. And, you’ve got the wonderful music.” (Watch CBC TV segment on dancing and Parkinson’s here.)
Research indicates that dance is an effective, complementary therapy, for those living with Parkinson’s disease, according to Rachel Bar, Manager, Health and Research Initiatives, at Canada’s National Ballet School, in Toronto. “More than 40 research studies have established its benefits,” she says.
Indeed, several Parkinson’s researchers funded by the Parkinson Canada Research Program, have studied the benefits of dancing for people with Parkinson’s, from symptom relief to improved mood and quality of life. One of these researchers Joseph DeSouzaconducts studies with participants at the Sharing Dance for People with Parkinson’s class and Dancing with Parkinson’s classes.
Research on dancing and Parkinson’s shows that improvements in balance and gait last long after dance classes end. DeSouza also wants people to know that dancing has other positive benefits. “All the other dance classes that take place all over the world show that people feel better – they’re happier,” DeSouza says. “It’s almost like a supplemental therapy that helps them cope with whatever they’re dealing with.”
Across the country, dance classes for people with Parkinson’s are gaining in popularity and several Parkinson Canada local offices and support groups are coordinating such offerings with local dance education instructors and partners.
In Saskatchewan, the Parkinson Canada Regina support group now offers a Creative Dance Movement for Parkinson’s class with dance instructor Fran Gilboy, who completed initial specialty training with Sarah Robichaud of Dancing with Parkinson’s in Toronto this past May. The support group first approached Gilboy last spring to offer a 30-minute dance class and then had her return for another session.
“After the first class, I was inspired by this group. After the second class, I was on my phone in the parking lot, trying to find a way to get funding to offer classes in an ongoing way,” she says. The Regina support group applied for a grant from the Saskatchewan Arts Board and was awarded a $9,400 grant to offer a program about twice a month from September through to April 2018.
“My heart strings were really pulled by this group,” says Gilboy, who has long taught creative dance to both children and adults. “There is a whole different level of pleasure in teaching this Parkinson’s group. There is the simple essence of joy in dance and other things just fall away. It’s now my favourite class,” she says.
Another outcome of the Saskatchewan grant is the production of a short documentary video to use to fundraise for further grants and support and future marketing of the program. The video will be shown at a Parkinson Canada gathering of support group facilitators in Saskatchewan and accompany a lecture and demonstration at a Parkinson Canada education conference in Saskatoon in April.
No experience is necessary and participants are encouraged to do what is possible for them on any given day.  Offered this first year free of charge, the classes take place at the Sunrise branch of the Regina Public Library at 3130 Woodhams Drive. The class is open to people with Parkinson’s, care partners, family members and friends. For more information, contact Rosemary Oddie at 306-585-0087 or email parkinsonsregina@gmail.com or John Dawes at 306-584-3267 or email john.dawes@sasktel.net.
In the Greater Toronto Area, Dancing with Parkinson’s classes are offered in more than a dozen locations, including each Monday from noon to 1 p.m. in the conference centre at the Parkinson Canada Toronto office at 4211 Yonge St. north of York Mills.  Contact Naseem Jamal at 416-227-3377 or Naseem.jamal@parkinson.ca to register.
Across the country, check with your local Parkinson Canada office for similar offerings or visit your local area’s Parkinson Canada event calendar, accessed here.
Canada’s National Ballet School offers Sharing Dance for People with Parkinson’s classes on Tuesdays and Fridays. You can find information about their program and other organizations offering dancing classes for people with Parkinson’s at www.dancepdnetwork.ca.
http://parkinsonpost.com/you-should-be-dancing/

Changes in brain connectivity correlates with Parkinson’s symptoms

Sep 21, 2017 | Milly Dawson




By using functional magnetic resonance imaging (fMRI) to study the organization of the brain’s connectome, researchers have shown certain alterations in the brain’s connectivity correlate with symptoms of Parkinson’s Disease (PD), such as motor disturbances.
The study—led by Xueling Suo with the Huaxi MR Research Center at the West China Hospital in Sichuan, China—was published online Sept. 4 in Radiology.
“We used resting-state fMRI imaging and graph theory approaches to investigate the topologic organization of the brain functional connectome and possible disease severity-related alterations in patients with PD,” wrote the researchers. “We found that patients with PD had topological functional disorganizations of brain networks.”
As compared to healthy controls, the connectomes of people with PD showed reduced local specialization and reduced global integration.
The study included 170 right-handed PD patients who were recruited between September 2013 and January 2016. They were compared with 81 right-handed, age- and sex-matched healthy controls.
“The configurations of brain functional connectome in patients with PD were perturbed and correlated with disease severity, notably with those responsible for motor functions,” according to Suo et al.
They found that decreases in the nodal centralities in the right precentral gyrus, left postcentral gyrus and left superior temporal gyrus, which were correlated with a higher Hoehn and Yahr stage, were observed in default-mode network regions.
“Decreased nodal centralities in the sensorimotor cortex were in accordance with the classic motor symptoms of PD,” they stated.
The researchers foresee their work furthering the understanding of the underlying neurobiology of this disease and advancing the development of new biomarkers for the progression of Parkinson’s disease.

http://www.healthimaging.com/topics/molecular-imaging/neuroimaging/changes-brain-connectivity-correlates-parkinson’s-symptoms

Back to basics: striving to stall Parkinson’s disease progression

 The Pharmaceutical Journal  21 SEP 2017    By Michele Solis

First described 200 years ago, Parkinson’s disease remains without a cure. After many failed clinical trials, researchers are getting back to basics to try to gain a better understanding of the challenges, and a new generation of treatment ideas are now in clinical trials, some of which aim to stall progression of the disease.

Source: DNA Illustrations / Science Photo Library

For seven years, 51-year-old Alison Ottaway managed to hide her Parkinson’s disease (PD). A low dose of levodopa, a drug that resupplies the brain with dopamine, which dwindles in the disease, kept her “cracking on [with] life as normal,” says Ottaway, who lives in Haslemere, Surrey. This meant working long hours in her busy career as an events planner.
Eventually this pace became physically difficult for Ottaway, and she scaled back her work. Then in 2016, her rigidity and freezing symptoms returned with a vengeance. This made it difficult for her to get out of bed, and sometimes she would have to drag herself across the floor to get through the house. Luckily, an increase in her levodopa dose got her back on track. This, along with exercise and self-care, keeps her symptoms at bay.
But the episode raises questions about how long levodopa will work for Ottaway. Her father also had early onset PD, and Ottaway watched him deteriorate over 23 years despite taking levodopa.
“I don’t know what the future brings,” she says. “When I need the next uplift [in dosage], will that work successfully? Or by then, would my body have got so used to the drug that it will have no effect at all?”

It is common for people with PD to have a levodopa “honeymoon” before its effectiveness declines. Other drugs that activate dopamine receptors may help, but these risk addiction or psychosis. Deep brain stimulation (DBS), in which an electrode is placed within the brain to activate neurons, has become routine for those unresponsive to drugs. But none of these options slow or stop the disease process, and PD, which was first described 200 years ago, remains without a cure.

In the past 20 years researchers have won important insights into the nature of the disease, but there are no new treatments to show for it. Many failed clinical trials later, pharmaceutical company investment has withered as PD is deemed too high risk. In response, researchers are getting back to basics: re-examining their animal models; monitoring PD symptoms over years to better understand the different ways the disease unfolds; looking for early signs of the disease; and refining clinical trials so that effective therapies will not be missed. With a better understanding of the challenges, a new generation of treatment ideas is now in clinical trials, some of which aim to stall progression of the disease.


Courtesy of David Dexter
David Dexter, deputy research director at Parkinson’s UK, says it has been a long time since effective drug therapies like levodopa have been developed for Parkinson’s disease

It’s been ages since real effective drug therapies have been developed like levodopa,” says David Dexter, deputy research director at Parkinson’s UK, a charity that funds PD research. “So we’re trying to get rid of all the roadblocks in drug design and testing. What we want is not only to get new molecules, but also to make the whole process more seamless and effective.”

The shaking palsy

PD was first described in 1817 by English doctor James Parkinson in an essay about six cases of “shaking palsy”. Now PD is known to affect 6.2 million people worldwide; in the UK, this is one person in 500[1]
A recognisable movement disorder, PD has symptoms that include rigidity, a shuffling walk and tremors. Less noticeable, but still debilitating, are non-motor symptoms such as cognitive impairment, and autonomic disruptions such as dizziness and heart rate problems. As the disease progresses, people become more unsteady and vulnerable to falls, which can lead to injuries and more illness. Unless prevention and treatments improve, PD’s toll will only increase as ageing populations grow.

Courtesy of Lorraine Kalia
Lorraine Kalia, a neurologist at University of Toronto, Canada, says the emerging complexity of Parkinson’s disease biology suggests that future treatment may involve multiple targets

“Parkinson’s disease is a disease you can live with for decades,” says Lorraine Kalia, a neurologist at University of Toronto, Canada. “So it’s a huge personal burden on people who have the disease and on their families, but also a huge social burden because of the costs for managing patients with this disease.”

PD is driven by the loss of dopamine-containing neurons in the brain, particularly those in the substantia nigra. For decades, researchers mimicked this pattern of cell death in animals using toxins, but the insights gleaned did not translate to humans, leading to a raft of failed clinical trials[2].
Focusing on why the cells die in the first place may be more fruitful. Researchers have zeroed in on a protein called alpha-synuclein, which becomes misshapen in PD and forms clumps called Lewy bodies inside the neurons. Though how exactly Lewy bodies are linked to cell death remains unclear, some suggest that alpha-synuclein misfolding is contagious between neurons, which may cause the disease to progress. Other signs of an ailing brain include worn out mitochondria, the energy sources for cells, and inflammation, which creates an unhealthy environment for neurons. A new study casts PD as an autoimmune disorder, with evidence that the immune system mistakenly attacks neurons and the alpha-synuclein protein[3].
The emerging complexity of PD biology suggests that future treatment may involve multiple targets. “Maybe you’re going to need three or four different things with a multitude of different actions to keep everything at bay,” says Kalia, who studies alpha-synuclein’s biology in multiple animal models. “Maybe you will take a drug that inhibits disease spread, and another drug to keep up mitochondria health, and another that keeps alpha-synuclein low.”
Figure 1: Proposed pathological roles of alpha-synuclein in Parkinson’s disease
Source: Nature Reviews Neuroscience
Alpha-synuclein becomes misshapen in Parkinson’s disease and forms clumps called Lewy bodies. These clumps may be toxic to neurons or may serve as reservoirs for toxic alpha-synuclein

Clearing clumps

Two research efforts are deploying antibodies to clear Lewy bodies from the brain, or at least prevent new protein clumps from forming. Prothena Biosciences, in South San Francisco, California, has partnered with Swiss multinational healthcare company Hoffmann-La Roche to test its antibody, PRX002, which binds preferentially to the aggregated form of alpha-synuclein. They reported in 2016 that high doses of PRX002 were safe and well-tolerated in people with PD; now a phase 2 study is under way to test whether this translates into a clinical benefit. Biogen, in Cambridge, Massachusetts, is also testing a similar antibody, while AFFiRiS AG in Vienna, Austria, is developing a vaccine to induce a person to produce their own alpha-synuclein antibodies.
However, missing from all of these studies is a brain imaging biomarker that would enable researchers to see Lewy bodies in the brain of a living person. Without one, it is impossible to monitor how well the antibodies are clearing alpha-synuclein. The need for a biomarker is so acute that the Michael J. Fox Foundation for Parkinson’s Research has offered a US$2m prize to the first group to develop one.
“While having this biomarker would be a valuable advance, even without it we are able to run studies based on well-defined endpoints that evaluate disease progression,” says Sarah Noonberg, chief medical officer at Prothena. Prothena’s study, which runs for two years, will rely on an assessment of motor symptoms.
Courtesy of Sarah Noonberg
Sarah Noonberg, chief medical officer at Prothena, says that having a biomarker for Lewy bodies would be a valuable advance

Similar immunotherapy has not fared well so far in Alzheimer’s studies, but PD researchers hope to sidestep any similar problems. The Alzheimer’s trials use antibodies to target beta-amyloid, the pathological protein in this disease, but they have been limited to low doses because of the potential oedema that comes from removing the protein from brain vessels. This side effect has not emerged as an issue for the alpha-synuclein trials.

Repurposed remedies

Rather than starting from scratch, some researchers are looking to established drugs as a shortcut to PD treatments. Already proven to be safe in humans, these include anti-diabetes medicines that quell inflammation, a blood pressure medicine that may stave off toxic calcium surges into dopamine neurons, and a supplement that may have antioxidant powers[2].
The rationale for one diabetes drug, pioglitazone, came from a study by Dexter and colleagues that found a 28% lower incidence of PD in those taking the drug compared with those taking other diabetes drugs[4]. Whether it makes a difference in people with PD is being tested; new results from a different diabetes drug, exenatide, look promising, since those on the drug for 48 weeks had reduced symptoms compared with those on placebo[5]. But there may be limits to what these drugs can do. By the time a person is diagnosed, they have already lost about 60–70% of dopaminergic neurons in the substantia nigra, Dexter says.
“So you’re trying to shut the stable door after the horse has bolted really,” he adds.
This difficult reality has researchers straining to identify early signs of PD. One predictor may be a condition called idiopathic rapid-eye movement (REM) sleep behaviour disorder, in which a person acts out their dreams[6]. Another early clue is loss of smell; though not specific to PD, this loss may pinpoint those at risk when considered in combination with other factors, such as dopamine deficits revealed by brain scans[7].
Another problem with drug trial design is that trials may miss subsets of people who would see positive results from an experimental treatment. For example, people with a rapidly deteriorating form of PD may benefit from a drug, but this effect may be washed out by no effect in those with a slowly progressing form. So far, studies lump all individuals with PD together.
To get a handle on the different types of PD progression, Parkinson’s UK and other funders have embarked upon longitudinal studies to follow people with PD over several years. With £11m sunk into these studies, the charity hopes to fundamentally change how PD trials are run and speed up therapeutic discoveries. For example, the results may reveal early signs that discriminate people with a rapid type of progression from those with slower deterioration, which could give way to more homogeneous patient groups and clearer conclusions in clinical trials. Also, this basic data combined with clinical trial data will be used by the Critical Path for Parkinson’s project to build computational models that simulate disease progression and clinical trial outcomes, which could help avoid expensive drug trial failures.

Cell therapy

Another avenue for new treatments lies in cell therapies, which are designed to revive or replace sickly dopamine neurons. This involves surgery to introduce either growth factors or new dopamine neurons into the brain. Despite sounding drastic, in reality, it is a relatively straightforward process, and similar to the procedure patients undergo if they opt for DBS.
“People are nervous about putting needles in the brain and having cells injected there. But neurosurgically, it’s not that big a challenge,” explains Stefan Irion, programme manager of the New York Stem Cell Science Consortia, based at Memorial Sloan Kettering Cancer Center in New York.
Experiments in the 1990s implanted brain tissue from human foetuses into the brains of people with PD, but had mixed success. These trials, which likely differed in the types of cells implanted, left researchers uncertain as to what worked and what didn’t. Today, researchers are working towards implanting homogenous dopamine neurons grown in the lab in unlimited quantities from stem cells. If successful, a single injection could provide a life-long fix for motor symptoms.
Courtesy of Stefan Irion
Stefan Irion (second from left), program manager of the New York Stem Cell Science Consortia, based at Memorial Sloan Kettering Cancer Center in New York, and his team are working on cell theapy for Parkinson’s disease

Getting to successful cell therapy may still be years off, but Irion predicts his group will begin human trials next year. To expedite the process, his group belongs to an international consortium called GForce-PD that provides a forum for researchers to evaluate each other’s ideas and data, and to come up with some standards for cell therapy.
“It is unique because essentially competing parties are sitting together at the same table and agreeing on certain standards that we set on ourselves,” Irion says.
Human trials of stem cells in PD have already begun in China and Australia. None of the procedures used to develop the cells for implantation in these studies have been published in peer-reviewed journals, however.
Other trials are seeking to supplement the brain with a growth factor that supports cell survival. One trial of glial cell line-derived neurotrophic factor (GDNF) in 41 people with PD has been completed by researchers at the University of Bristol. The final results are pending, but one issue that has emerged in this and other PD trials is the potential for a placebo response: some who received a “sham” procedure or sugar pill may report and show improvements. Dexter says the intensive attention a person gets during a PD trial may well stimulate the brain’s reward circuitry, including its dopamine neurons.
Using a mobile phone app that periodically prompts a person to answer questions about their symptoms as they go about their daily activities may lessen the placebo response.
“You might get much more of an even picture of how they’re doing [with a mobile app] because a neurologist isn’t standing over them doing the assessment,” Dexter says.
Such a platform has been used to compile health data from people with PD and healthy controls in a global “people-centred project” called 100 for Parkinson’s.
Attention to the day-to-day realities matters to people with PD, such as Ottaway. When levodopa’s help waned, she realised she had to let go of full-time employment and spend more time on exercise and self-care. She urges people at a similar point to find other ways of remaining engaged with life.
“As soon as my father’s brain stopped, his body stopped. As soon as his body stopped, he became a recluse in his own home and in his own body,” Ottaway says. “We must continue to be active in both body and mind as best we can.”

NICE updates Parkinson’s guideline

In July 2017, the National Institute for Health and Care Excellence (NICE) released new guidance on Parkinson’s disease, which hadn’t been updated since 2006[8]. Of note was the official elevation of levodopa to a first-line treatment for those whose motor symptoms start to interfere with their quality of life, says Janine Barnes, a neurology specialist pharmacist in Dudley, West Midlands, who helped draft the new guideline.
Courtesy of Janine Barnes
Janine Barnes, a neurology specialist pharmacist in Dudley, West Midlands, helped draft the new guidance on Parkinson’s disease published by the National Institute for Health and Care Excellence

“The old idea was to wait with the levodopa, because it was only going to work for seven to ten years,” she says. “But the current thinking is to give it now, when people are more mobile and their quality of life can be improved more.”

Other highlights:

  • A larger group of medicines, including levodopa, MAO-B inhibitors and dopamine agonists, can be selected to treat Parkinson’s symptoms when motor symptoms do not impact on quality of life;
  • Choose a non-ergot-derived dopamine agonist in most cases in view of the monitoring required for ergot-derived dopamine agonists;
  • Consider deep brain stimulation for advanced PD when symptoms cannot be adequately controlled by best medical therapy;
  • Be aware that dopamine therapies for PD, particularly dopamine agonists, raise the risk of impulse control disorders, such as compulsive gambling, hypersexuality or binge eating;
  • It is important to manage the non-motor symptoms of PD, including daytime sleepiness, postural hypotension, depression, psychosis and dementia, as these often affect quality of life more than the motor symptoms.

References:

[1] GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1545–1602. doi: 10.1016/S0140-6736(16)31678-6
[2] Kalia LV, Kalia SK & Lang AE. Disease-modifying strategies for Parkinson’s disease. Mov Disord 2015;30: 442–1450. doi: 10.1002/mds.26354
[3] Sulzer D, Alcalay RN, Garretti F et al. T cells from patients with Parkinson’s disease recognize alpha-synuclein peptides. Nature 2017;546:656–661. doi: 10.1038/nature22815
[4] Brauer R, Bhaskaran K, Chaturvedi N et al. Glitazone treatment and incidence of Parkinson’s disease among people with diabetes: a retrospective cohort study. PLoS Med 2015;12:e1001854. doi: 10.1371/journal.pmed.1001854
[5] Athauda D, Maclagan K, Skene SS et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet 2017; pii:S0140–6736(17)31585–4. doi: 10.1016/S0140-6736(17)31585-4
[6] Iranzo A, Santamaria J & Tolosa E. Idiopathic rapid eye movement sleep behavior disorder: diagnosis, management, and the need for neuroprotective interventions. The Lancet Neurol2016;15:405–419. doi: 10.1016/S1474-4422(16)00057-0
[7] Jennings D, Siderowf A, Stern M et al. Conversion to Parkinson disease in the PARS hyposmic and dopamine transporter-deficit prodromal cohort. JAMA Neurol 2017; 74;933–940. doi: 10.1001/jamaneurol.2017.0985
[8] National Institute for Health and Clinical Excellence. Parkinson’s disease in adults. NICE guideline (NG71). Available at https://www.nice.org.uk/guidance/ng71 (accessed September 2017).
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