Bath Middle School student raises money for Parkinson’s through running

 December 26, 2018

Bath Middle School student Lily Wright is raising money for Parkinson’s disease with her passion for running. (Nathan Strout/The Times Record)

BATH – Not many middle schoolers decide to spend their time trying to help cure a disease that affects millions of people. But that’s exactly what Bath Middle School student Lily Wright has done.

The seventh-grade student has gone above and beyond the standard requirements of a class assignment to practice advocacy skills. She has already run one race to raise money for Parkinson’s disease research and plans to run another one on New Year’s Eve. Already she’s raised $580 for the cause.

The impetus for Wright’s fundraising efforts came from an advocacy project assigned by her teacher at Bath Middle School, Maria Newcomb.

“The advocacy project is something I’ve done in the past, but I haven’t done it in the last three years. It’s basically an opportunity for the students to choose any topic related to wellness (and advocate for it), and I always encourage them to choose something they’re passionate about, something they care about,” said Newcomb.

It wasn’t difficult for Wright to think of an area where she had been personally affected by a health issue. Two of Wright’s grandparents have been diagnosed with Parkinson’s.

“It was the first thing that came to my mind,” said Wright. “I was like, ‘You know what? I should do Parkinson’s disease because not everybody knows about that.’”

Parkinson’s is a debilitating disease that affects the central nervous system. Over time, the disease impacts people’s motor skills and can eventually impact their behavior. According to the Parkinson’s Foundation, more than 10 million people are living with the disease worldwide, and 60,000 Americans are diagnosed annually.

“There’s no cure for it,” said Wright. “There’s all these people who don’t have a cure and they’ve lost all their abilities to, like, do all the things they love, like running or working out somewhere.”

Wright said she has already begun to see how the disease has affected her grandparents.

“Over time, I’ve seen their abilities change. A few years ago, my grandmother took me on a trip to the Grand Canyon. She was so able and willing to do that with all of her grandchildren. Then she had a sickness come this August and that kind of made her take a step back,” said Wright. “That kind of made me sad.”

“My grandfather used to play squash. (He doesn’t) have the ability to do that anymore,” she added.

Wright knew what she cared about, but how would she advocate for it?

Students work on their projects one day a week on their project over the course of a semester, explained Newcomb, conducting research on the topic of their choice and developing their approach to advocacy. Some students chose to make a flyer or brochure, while others have written announcements to go out over the intercom. Topics range from raising self-esteem to fundraising for the Midcoast Humane Society.

Wright decided to draw on one of her passions for her advocacy project.

“I love running. I don’t know where I got that from,” said Wright. “I’m not on a track team or anything, (though) I like doing team sports. I do soccer and lacrosse and those involve running a lot.”

In September, Wright ran her first race–a 5K in Camden as part of the Camden Snow Bowl.

With some encouragement from her mother, Wright decided to kick her project up a notch using her love for running. Cutting through the noise of brochures and announcements, Wright set a goal to raise $500 for Parkinson’s research by running a 5K in November. All of the money raised would go to The Michael J. Fox Foundation to be used for Parkinson’s research.

“I thought I was not going to get close to that,” admitted Wright.

Still, Wright was committed to running the race–even though it was pouring rain on race day.

“When my mom told me it was raining, I was like, ‘Eh, whatever,’” said Wright. “She told me I was crazy and I was like, yup.”

Wright finished the race, raising $580 in the process, surpassing her original goal. She even got second place in her age group.

Inspired by that success, Wright has decided to continue running to raise money for Parkinson’s research.

“I immediately went online and asked, ‘What’s the next race I can do? It’s going to be so cold, but I’m doing it!” she said.

On Monday, December 31, she will be participating in the 5K Polar Bear Dip and Dash in Portland. Not only does that race involve running five kilometers in the Maine winter, it culminates in a quick dip into the ice-cold waters of the Atlantic in January. It’s not an activity for the faint-hearted.

“I’m psyched for it,” said Wright.

While that race is ostensibly meant to raise awareness of climate change, Wright will use it as the next step in her journey to raise money for Parkinson’s research.

Those looking to support Wright’s efforts and fund Parkinson’s research can donate at fundraise.michaeljfox.org/tf-2018/LilyfightsPD.

https://www.timesrecord.com/articles/front-page/bath-middle-school-student-raises-money-for-parkinsons-through-running/

Losing neurons is sometimes not all bad

December 27, 2018, Champalimaud Centre for the Unknown

Neurons in red are the unfit neurons that will be killed for the better functioning of the whole brain, marked in blue. Credit: Dina Coelho (CCU)

Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease. But a new study suggests that neuronal death may actually be a protective reaction against the disease. This could lead to a complete rethinking of therapeutic approaches to Alzheimer's.

For the first time, scientists at the Champalimaud Centre for the Unknown (CCU) in Lisbon, Portugal, have shown that neuronal cell death in Alzheimer's disease (AD) may actually not be a bad thing—on the contrary, it may be the result of a cell quality control mechanism trying to protect the brain from the accumulation of malfunctioning neurons. Their results, which were obtained using fruit flies that had been genetically modified to mimic the symptoms of human AD, were published in the journal Cell Reports.

The cell quality control mechanism at play is called cell competition. It leads to the selection of the fittest cells in a tissue by enabling a "fitness comparison" between each cell and its neighbors—with the fitter cells then triggering the suicide of less fit ones.

It has been recently shown that cell competition is a normal, powerful anti-aging mechanism in the body in general and in the brain in particular. "In 2015, we discovered that clearing unfit cells from a tissue was a very important anti-aging mechanism to preserve organ function, says Eduardo Moreno, principal investigator of the Cell Fitness lab at the CCU.

His team reasoned that, if these fitness comparisons happened in normal aging, they could also be involved in neurodegenerative diseases associated with accelerated aging, such as Alzheimer's, Parkinson's disease or Huntington's disease, Moreno explains. "This had never been tested," he says. In collaboration with Christa Rhiner's Stem Cells and Regeneration lab at the CCU, they started by testing AD hallmarks in fruit fly models of the disease.

For this, they bred fruit flies that had been genetically manipulated to express in their brain the human amyloid-beta protein, that forms aggregates in the brains of AD patients. The formation of amyloid-β aggregates in the brain is a crucial step in the development of AD.

The transgenic flies displayed symptoms and pathologies similar to those of AD patients: "they showed loss of long-term memory, accelerated aging of the brain and motor coordination problems, all of which got worse with age", specifies Christa Rhiner, whose team studied the cognitive and motor functions of the flies.

The first thing the scientists wanted to do was to see whether in these flies, neuronal death was indeed activated by the process of fitness comparison—in other words, "that the neurons were not dying on their own but being killed by fitter neighbors," Moreno points out.

"When we started, the current view was that neuronal death must be always detrimental. And much to our surprise, we found that neuronal death actually counteracts the disease," says Dina Coelho, first author of the study. What happened was that when she blocked neuronal death in the flies' brain, the insects developed even worse memory problems, worse motor coordination problems, died earlier and their brain degenerated faster.

However, when she boosted the fitness comparison process, thus accelerating the death of unfit neurons, the flies expressing the AD-associated amyloid-beta proteins showed an impressive recovery. "The flies almost behaved like normal flies with regard to memory formation, locomotive behavior and learning," says Rhiner, and this at a time point where the AD flies were already strongly affected.

This means that the anti-aging mechanism in question keeps working well in Alzheimer's disease and shows that, in fact, "the neuronal death protects the brain from more widespread damage and therefore the neuronal loss is not what is bad, it is worse not to let those neurons die", Moreno emphasizes. "Our most important finding is that we have probably been thinking the wrong way about Alzheimer's disease. Our results suggest that neuronal death is beneficial because it removes neurons that are affected by noxious beta-amyloid aggregates from brain circuits, and having those dysfunctional neurons is worse than losing them" Moreno concludes.

The results could have crucial therapeutical implications. "Some molecules have already been identified as potential inhibitors of cell suicide, and some experimental drugs exist, and are being tested which inhibit those inhibitors of cell death, therefore accelerating neuronal death," says Moreno.

But he cautions: "This work has been done in fruit flies." It will be necessary to see, whether these results on neuronal death in Alzheimer's also hold true for humans.

Journal reference: Cell Reports

Provided by: Champalimaud Centre for the Unknown

https://medicalxpress.com/news/2018-12-neurons-bad.html

Kicking, yelling during sleep? Study finds risk factors for violent sleep disorder

December 26, 2018, American Academy of Neurology

Taking antidepressants for depression, having post-traumatic stress disorder or anxiety diagnosed by a doctor are risk factors for a disruptive and sometimes violent sleep disorder called rapid eye movement (REM) sleep behavior disorder, according to a study published in the December 26, 2018, online issue of Neurology, the medical journal of the American Academy of Neurology. The study also found men are more likely to have the disorder.

REM sleep is the dream state of sleep. During normal REM sleep, your brain sends signals to prevent your muscles from moving. However, for people with REM sleep behavior disorder, those signals are disrupted. A person may act out violent or action-filled dreams by yelling, flailing their arms, punching or kicking, to the point of harming themselves or a sleep partner.

"While much is still unknown about REM sleep behavior disorder, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson's disease, dementia with Lewy bodies or multiple system atrophy," said study author Ronald Postuma, MD, MSc, of McGill University in Montreal, Canada, and a member of the American Academy of Neurology. "Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it."

The study looked at 30,097 people with an average age of 63. Researchers screened participants for a variety of health conditions and asked about lifestyle, behavior, social, economic and psychological factors.

In addition, every participant was asked, "Have you ever been told, or suspected yourself, that you seem to act out your dreams while asleep?"

Researchers then identified 958 people, or 3.2 percent, with possible REM sleep behavior disorder, after excluding participants with Parkinson's disease, dementia, Alzheimer's disease or sleep apnea.

Researchers found those with the disorder were over two-and-a-half times as likely to report taking antidepressants to treat depression, with 13 percent of those with the disorder taking them compared to 6 percent of those without the disorder. People with the disorder were also two-and-a-half times as likely to have post-traumatic stress disorder. They were twice as likely to have mental illness, and over one-and-a-half times as likely to have psychological distress.

Other findings were that men were twice as likely as women to have possible REM sleep behavior disorder; 59 percent of those with the disorder were male, compared to 42 percent of those without the disorder. People with possible REM sleep behavior disorder were 25 percent more likely than those without the disorder to be moderate to heavy drinkers, with 19 percent of those with the disorder moderate to heavy drinkers compared to 14 percent of those without the disorder. They had slightly less education, an average of 13.2 years of education compared to an average of 13.6 years for those without the disorder. They also had lower income and were more likely to have smoked.

"Our research does not show that these risk factors cause REM sleep behavior disorder, it only shows they are linked," said Postuma. "Our hope is that our findings will help guide future research, especially because REM sleep behavior disorder is such a strong sign of future neurodegenerative disease. The more we understand about REM sleep behavior disorder, the better positioned we will be to eventually prevent neurologic conditions like Parkinson's disease."

A limitation of the study was that 96 percent of participants were white, 

meaning the results may not apply to people of other ethnic backgrounds.

Journal reference: Neurology 

Provided by: American Academy of Neurology 

https://medicalxpress.com/news/2018-12-factors-violent-disorder.html

Early Investment from Michael J. Fox Foundation Pushes New Parkinson's Treatment to Market

NEW YORK, Dec. 26, 2018 

The Michael J. Fox Foundation for Parkinson's Research (MJFF) announces the first regulatory approval of a Parkinson's treatment funded by the Foundation. Inbrija from Acorda Therapeutics, Inc. received approval from the U.S. Food and Drug Administration on December 21, 2018, for the treatment of "off" episodes, when Parkinson's symptoms are not well controlled with oral medication. 

"Our strategy of funding high-risk, high-reward projects with a focus on patient impact has paid off," said MJFF CEO Todd Sherer, PhD. "Today people with Parkinson's have a new option to manage life with the disease. Because of our Foundation's investments, many more treatments to manage symptoms and to stop progression are moving closer to pharmacy shelves and patient hands."

The Foundation partially funded Phase I and II trials of Inbrija — an inhaled powder of the gold-standard Parkinson's medication levodopa — by biotechnology company Civitas Therapeutics in 2011 and 2013 with two grants totaling $1.3 million. After multiple rounds of venture capital investment, Acorda Therapeutics acquired Civitas in 2014 and continued the development of Inbrija. 

De-risking Investments for Larger Partners

MJFF provides early-stage therapeutic projects with the capital needed to advance. Grantees use its funding to build evidence of safety and efficacy, which can attract larger partners with resources for later-stage testing, regulatory processes, and commercialization. The Foundation directs its donor-raised funds to the areas of most pressing patient need: from better symptom management to treatments to slow, stop or even prevent Parkinson's progression. 

"The way The Michael J. Fox Foundation does it is really best in class. The lack of bureaucracy and obstacles encourages emerging companies to seek funding and engagement and ultimately advance their projects," said Glenn Batchelder, co-founder and former CEO of Civitas Therapeutics and member of the MJFF Board of Directors. 

This "de-risking" model has advanced dozens of Parkinson's therapies. Treatments with potential to slow or stop the disease are marching through clinical trials with new partners after early MJFF funding. Therapies targeting individual symptoms are experiencing similar momentum, and the Food and Drug Administration is currently reviewing another MJFF-funded Parkinson's treatment for "off" episodes: APL-130277 from Sunovion Pharmaceuticals.

New Option for Unmet Patient Need

The newly approved Inbrija helps quickly alleviate symptoms of tremor, slowness and stiffness. With long-term oral levodopa use and advancing disease, these aspects of the disease can re-emerge between medication doses. These "off" episodes can greatly impact quality of life, bringing uncertainty to one's days and limiting ability to complete daily tasks.

A 2014 MJFF survey of more than 3,000 people with Parkinson's disease found that more than 60 percent of respondents were in an "off" state for two or more hours per day and nearly 50 percent said their "off" episodes caused them to avoid or stop activities.

Acorda Therapeutics CEO Ron Cohen notes, "It was clear thanks to the work of MJFF that 'off' episodes were a serious symptom for many Parkinson's patients. Acorda committed to addressing this, and the FDA approval means patients will soon have a new treatment option."

Acorda and The Michael J. Fox Foundation are collaborating on a number of projects, including a study of how patients, care partners and doctors discuss "off" episodes to identify gaps in communication and thereby optimum care.

About The Michael J. Fox Foundation for Parkinson's Research

As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $800 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. 

For more information, visit www.michaeljfox.org.

SOURCE The Michael J. Fox Foundation for Parkinson's Research

Related Links

http://www.michaeljfox.org

https://www.prnewswire.com/news-releases/early-investment-from-michael-j-fox-foundation-pushes-new-parkinsons-treatment-to-market-300770763.html

FDA Approves Inhaled Levodopa for Parkinson's

• by Judy George, Contributing Writer, MedPage Today 
  December 26, 2018
    Improved motor function when taken during 'off' episodes

The FDA approved levodopa inhalation powder (Inbrija) for on-demand use during "off" episodes in people with Parkinson's disease taking an oral carbidopa-levodopa regimen, Acorda Therapeutics announced.

These "off" periods are defined as the return of Parkinson's symptoms when dopamine levels are low between carbidopa-levodopa doses. For faster action, the levodopa powder bypasses liver metabolism as it moves from the lungs to the bloodstream.

The FDA nod came after the phase III SPAN-PD pivotal efficacy trial showed a significant improvement in motor function at 12 weeks -- as assessed by Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores 30 minutes after dosing -- among patients who used 84 mg of inhaled levodopa compared with placebo (-9.83 vs -5.91, P=0.009). For some patients, onset of action was as early as 10 minutes. The most common adverse reactions were cough, upper respiratory tract infection, nausea, and discolored saliva or spit.

A phase III open-label study also assessed the safety and tolerability of inhaled levodopa (formerly CVT-301) over 12 months and showed that the average reduction in forced expiratory volume in 1 second (FEV1) from baseline was the same for the inhaled levodopa group as an observational control group. Patients with chronic obstructive pulmonary disease (COPD), asthma, or other chronic respiratory diseases within the last 5 years were not included in this study.

An FDA decision about this levodopa inhalation powder was expected in October, but in September, the agency extended its time frame to review additional information about the drug's chemistry and manufacturing.

In an Acorda press release, Todd Sherer, PhD, CEO of the Michael J. Fox Foundation -- which funded early studies of inhaled levodopa -- said "patients told us that 'off' periods were one of their most serious issues. We knew we had to help address this unmet need, and this approval is a significant step forward for the community as it provides a new option to manage these gaps in symptom control."

Inhaled levodopa is not for patients who have used a nonselective monoamine oxidase inhibitor such as phenelzine (Nardil) or tranylcypromine (Parnate) in the last 2 weeks. 

Full prescribing information is online at:

http://www.inbrija.com/prescribing-information.PDF

The drug should be available in the first quarter of 2019.

https://www.medpagetoday.com/neurology/parkinsonsdisease/77104

Preventing the Progression of Parkinson's Disease

Free Educational Conference Tuesday, January 8, 2019 at Parkinson Place. Topics include: Preventing the Progression, Healthy Cooking and Nutrition for Parkinson's! RSVP Reservation@Parkinsonhope.org

FoxFeed Blog: Inhaled Levodopa for 'Off' Time Approved by FDA

Posted by  Rachel Dolhun, MD,    December 22, 2018

On December 21, 2018, the U.S. Food and Drug Administration (FDA) approved Inbrija, an inhaled levodopa powder, for "off" episodes in people with Parkinson's disease treated with levodopa/carbidopa. The Michael J. Fox Foundation funded early clinical trials of this therapy, the first to reach market approval with early de-risking from our Foundation. 

Read more on this therapy below and in a press release from Acorda Therapeutics, Inc.:

https://www.businesswire.com/news/home/20181221005620/en/Acorda-Therapeutics-Announces-FDA-Approval-INBRIJA™-levodopa

 We'll share more in the coming weeks on the impact of this new medication for people with Parkinson's and on our Foundation's role in its development.

---

UPDATE September 13, 2018: Acorda Therapeutics, Inc today announced that the FDA has extended its decision date on inhaled levodopa to January 5, 2019. According to a press release, the extension is related to submission of additional information on the drug’s chemistry and manufacturing that will take additional time for the FDA to review. 

---

POSTED February 20, 2018: Today, Acorda Therapeutics, Inc. announced that the FDA filed its New Drug Application (NDA) for inhaled levodopa. (If approved, the drug will be called Inbrija.) This is the last step in the lengthy drug development and approval process. Now, the FDA reviews everything that is known about inhaled levodopa -- clinical trial data, how the drug works and how it's made. This review process is how the FDA determines whether to approve a new therapy, and Acorda expects a decision no later than October 2018.

Inhaled levodopa is a potential new way to treat "off" times -- periods when Parkinson's symptoms, such as tremor, slowness and stiffness, emerge because medication isn't working well. These "off" times can come on gradually, before it's time to take the next medication dose, or unexpectedly and unpredictably. Inhaled levodopa is an add-on, as needed medication for people who are already taking levodopa drugs, such as Sinemet, but are experiencing "off" times. Some liken inhaled levodopa to the asthma medication inhaler. People with asthma may take a puff from an inhaler when they have trouble breathing. Similarly, some with Parkinson's may soon be able to take a breath of levodopa when they have trouble moving.

"People with Parkinson's and physicians need more options to manage this disease," says Todd Sherer, PhD, CEO of The Michael J. Fox Foundation. "Inhaled delivery of levodopa could help the many people living with Parkinson's facing the complication of 'off' periods as their disease progresses."

The Michael J. Fox Foundation funded Phase I and II studies of inhaled levodopa.

https://www.michaeljfox.org/foundation/news-detail.php?inhaled-levodopa-for-off-time-moves-to-fda-review

Parkinson’s breakthrough – Disease could be treated with stem cells injected into the brain

Joe Mellor    December 20, 2018

Parkinson’s disease really could be treated with stem cells injected into the brain, say Scottish scientists.

They have created cells resistant to the devastating neurological condition – offering hope of restoring normal movement and balance.

Many patients have long pinned hope on the therapy as a potential cure. The first clinical trial started in Japan in August.

Now a University of Edinburgh team have formed stem cells – which have the ability to turn into any cell type – that can’t develop Parkinson’s in the first place. It overcomes a major obstacle in the approach as, over time, transplanted tissue has been able to acquire signs of the disease from nearby cells.

Study leader Dr Tilo Kunath, of the Medical Research Council’s Centre for Regenerative Medicine lab, said: “We know Parkinson’s spreads from neuron to neuron, invading healthy cells.

“This could essentially put a shelf life on the potential of cell replacement therapy. Our exciting discovery has the potential to considerably improve these emerging treatments.”

The study, published in the European Journal of Neuroscience, is a key step towards making stem cell therapy a viable option for Parkinson’s.

It causes progressive loss of neurons that release the vital nerve transmitter chemical dopamine – necessary for controlling body movement.

This leads to symptoms such as tremors and shaking. Sufferers include comic Sir Billy Connolly, Sweet Caroline singer Neil Diamond and actor Michael J Fox whose charity has been funding research for years.

The latest advance could markedly improve stem cell therapy for the condition, which affects around one in 350 people in the UK. It involves transplanting healthy cells into the damaged parts of the brain.

Dr Kunath and colleagues snipped out sections of DNA from human stem cells using the editing technique known as CRISPR where a chemical is used like a pair of ‘molecular scissors’. In doing so, they removed a gene linked to the formation of toxic clumps, known as Lewy bodies, which are typical of Parkinson’s brain cells.

In tests, the cells were transformed into neurons that produce dopamine – the brain chemical lost in Parkinson’s – in a dish.

After treatment with a specific molecule those that had been gene-edited did not form the toxic clumps, while unedited ones displayed signs of Parkinson’s.

The breakthrough may be most beneficial to younger patients living with Parkinson’s and those with an aggressive form of the condition. The next step is human trials.

The Cure Parkinson’s Trust, which part funded the study with the UK Centre for Mammalian Synthetic Biology and the pharmaceutical company UCB Biopharma, said it was “thrilled”.

Deputy director Dr Simon Stott said: “Cell replacement therapy represents one experimental approach to regenerative medicine for people with Parkinson’s.

“This new research by Dr Tilo Kunath and his team at the University of Edinburgh provides another advancement in the development of this treatment. “The Cure Parkinson’s Trust is thrilled to be associated with this inspiring and innovative research.”

Last year the Japanese scientists carrying out the first human trial of stem cell therapy for Parkinson’s successfully restored nerve cells destroyed by a similar condition in monkeys.

The animals, suffering an artificially induced version of the disease, showed significant improvement two years after having precursor dopamine neurons derived from human stem cells transplanted into their brains.

Prof Jun Takahashi, a Parkinson’s neurosurgeon from Kyoto University, who led the research, said at the time: “The monkeys became more active after cell transplantation: moved more rapidly and more smoothly, and showed more various type of movements and less tremor.”

Parkinson’s is the second most common neurodegenerative disease – a chronic, degenerative neurological disorder, mainly affecting the motor system. It is caused by a shortage of dopamine that enables messages to be sent to the parts of the brain that control movement and some forms of thinking.

Parkinson’s, which is currently incurable, affects approximately one in 100 people over the age of 60. Numbers of people living with the disease are estimated to be at least 130,000 in the UK, one million in the US and five to seven million worldwide. Currently, standard medications used to treat Parkinson’s improve early symptoms but as it progresses and dopaminergic neurons continue to be lost, the drugs eventually become ineffective.

Scientists are investigating how regenerative medicine and stem cell science could be used to treat or prevent Parkinson’s.

The disorder’s underlying cause is still unknown, but researchers do know which cells and areas of the brain are involved, and have been experimentally successful in using stem cells to grow dopamine-producing nerve cells in the lab.

By Mark Waghorn

https://www.thelondoneconomic.com/lifestyle/parkinsons-breakthrough-disease-could-be-treated-with-stem-cells-injected-into-the-brain/20/12/

Pain in Parkinson’s Disease: A Spotlight on Women

By Kristin Della Volpe

Practical Pain Management interviewed Jori E. Fleisher, MD, MSCE, assistant professor of neurology and population health at The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Medical Center (New York CIty), a Parkinson’s Foundation Center of Excellence, about the challenges facing women with Parkinson's disease.

Practical Pain Management interviewed Jori E. Fleisher, MD, MSCE, assistant professor of neurology and population health at The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Medical Center (New York CIty), a Parkinson’s Foundation Center of Excellence, about the challenges facing women with Parkinson's disease.

Q. What is the pain experience in PD, and does it differ between genders?

Dr. Fleisher: As with almost everything else in PD, the pain experience is highly individualized, and no 2 people, regardless of gender, will have the same symptoms. Female gender appears to be an independent risk factor for chronic pain in PD, even though PD is more common in men than in women.² Pain intensity also is higher in women than in men with PD.¹

There is a lot of interesting research examining the contributions of hormones to the greater prevalence of PD in men or, conversely, the lower prevalence in women.³Once we better understand the roles of sex hormones in the pathophysiology of PD, we may better understand whether hormones also play a role in the higher incidence of chronic pain in women with PD.

Q. What are the causes of pain in PD?

Dr. Fleisher: There are 4 primary types of pain in PD: musculoskeletal, dystonic, neuropathic, and central pain.²

• Musculoskeletal pain typically is related to involuntary muscle rigidity or bradykinesia, which limits range of motion. For example, it is not uncommon for people with PD to present initially with unilateral shoulder pain (ie, frozen shoulder) for which they have undergone numerous orthopedic and pain management consultations, as well as failed injections and surgeries, before they consult with a neurologist or a movement disorder specialist and are correctly diagnosed with PD.
• Dystonic pain usually manifests as painful curling or bending of the toes/fingers or inversion of one foot but can occur in any area of the body. Sometimes, dystonic pain is a sign of extremely low dopamine levels, especially when it occurs first thing in the morning or late at night.
• Neuropathic pain in PD commonly is related to neuroforaminal compression in the spine resulting from degenerative disc disease, but it also may be related to nerve compression that causes a twisting of the spine in a person with dystonia, or postural deformities related to PD.
• Central pain is relatively rare, occurring in approximately 10% of people with PD at some point.⁴ Symptoms include a vague gnawing, boring, or deep, aching pain that is often hard to describe and may be unrelenting. In some cases, central pain can show up as abdominal pain or a feeling of reflux without a clear etiology. Rarely, people with PD may have perioral/oral pain or genital pain as a manifestation of this central pain syndrome. Because the symptoms of central pain are vague and the syndrome is poorly understood by nonpain specialists, there may be a tendency for physicians and healthcare providers to minimize the symptoms or at least not recognize them as a part of PD.

Q. Are there any gender disparities in the treatment of pain in PD?

Dr. Fleisher: I don’t think there is any literature demonstrating gender disparities in pain treatment among patients with PD, but we do know that there are certainly gender disparities overall in the treatment of women with PD, so it would not be surprising to learn that women with PD-related pain are at a disadvantage and not getting the appropriate care that they need.

Q. What is the role of depression in the pain experience in PD?

Dr. Fleisher: Depression is one of the most overlooked symptoms of PD, and it can affect over 30% of people with the disease at some point in their illness.⁵ I think there is a misconception that depression results from an adjustment disorder following diagnosis. While that may be partially true, patients with PD have alterations in various neurotransmitters—including serotonin and norepinephrine in addition to dopamine—that predispose them to depression.^6,7

Depression is the primary factor related to quality of life in PD and is an independent risk factor for medication nonadherence. A physician could prescribe the most comprehensive regimen to control Parkinson’s symptoms, including pain, but if depression symptoms are not being addressed simultaneously, the likelihood that that person is going to take that regimen is pretty minimal.

Given the link between depression and chronic pain, patients who are depressed should be screened for chronic pain and vice versa. In my practice, we screen every patient with the Unified Parkinson’s Disease rating scale , which has both a patient-reported subjective component that includes questions about depression, pain, and altered sensation, as well as an objective component that includes a physical examination and questions about potential medication adverse effects (AEs). The patient fills out the subjective component every single time they come to the office.

Q. What role does exercise play in pain management in PD?

Dr. Fleisher: Exercise and physical therapy can be tremendously helpful in managing pain in PD, in addition to being important for overall disease management.^4,8 Evidence suggests that exercise is the best option we have to alter the course of PD, and it has been shown to promote neuroplasticity and neurorestoration in PD^.9,10 In addition, research suggests that exercise can activate both dopaminergic and non-dopaminergic inhibitory pain pathways, which may help to modulate the experience of pain in PD.¹⁰

Good exercise options include walking, swimming, dancing, and using a recumbent bike. In particular, forms of dance with smooth movements and those that encourage bigger steps appear to be especially beneficial in helping retrain the brain that the shuffling gait of PD is not the norm. Incredible work has come out of the Mark Morris Dance Company, in New York City, which has started a Dance for PD class that has spread throughout the country. In addition, yoga and tai chi can help with balance and core strength, which are critical for people with PD.

Importantly, there doesn’t appear to be an upper limit for the benefits of exercise on the disease. I encourage patients to aim for at least 30 to 45 minutes a day at least 3 to 4 days a week. Patients who are sedentary should start with 5 minutes per day for a week, and then increase the duration each week.

One way to incentivize exercise is to reserve your favorite television shows only for times that you are exercising. This can be helpful in motivating people to stick with a regimen. If a patient is going to binge watch TV, they should reserve that time for when they are on a recumbent bike, treadmill, or elliptical machine.

Q. Which pharmacotherapies are best for treating pain in PD?

Dr. Fleisher: The first step is to make sure that Parkinson’s medications are optimized. For example, dystonic or musculoskeletal pain may be caused by Parkinson’s motor symptoms (eg, rigidity, bradykinesia, dystonia) when dopamine levels are too low. If the patient is able to keep a pain diary, it may show a clear pattern of pain occurring the hour before each dose or before specific doses, suggesting the need to either increase the dosage preceding the pain episode, increase the frequency of medication dosing, or use adjunctive dopaminergic therapies to achieve more steady dopamine levels throughout the day.

In addition, optimal management of comorbidities (eg, diabetes, osteoarthritis, depression) that may contribute to pain is needed. The choice of pain medication depends on the pain type.

The first lines of treatment for musculoskeletal pain can be heat and cold packs and nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen.  

For dystonic pain, adjustment of dopaminergic medications is particularly critical; however, if dystonia consistently occurs in 1 particular body part, botulinum toxin injections also can be helpful. The goal of botulinum toxin injection is to weaken the muscle enough to stop the abnormal contractions and twisting, but the patient may lose function in the body part as a result (eg, foot drop). Thus, patient counseling is important to manage expectations.

For neuropathic pain, anticonvulsants such as gabapentin (Neurontin, Gralise, others) or pregabalin (Lyrica) can be effective. As second-line therapy, tricyclic antidepressants may be effective. However, in many patients, the adverse effects of those medications, particularly the anticholinergic effects (eg, confusion, dry mouth, urinary retention, or constipation)—which patients already may experience as symptoms of PD—outweigh the benefits.

Central pain is the most difficult type of pain to treat. Antidepressants (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or atypical antidepressants) or anticonvulsants (gabapentin or pregabalin) may be helpful. In select cases, opioids may be necessary. Consultation with a pain management specialist for additional expertise is warranted in these difficult cases.

When treating women of childbearing age, it is important to make sure that medications are appropriate for women who are pregnant or breastfeeding or who want to become pregnant. Consultation with the patient’s OB/GYN may be warranted in some cases to rule out contraindications.

Q. Are there any alternative therapies that are effective for pain in PD?

Dr. Fleisher: Although alternative therapies may be helpful, there is little evidence-based research to support their use. Certainly massage therapy, anecdotally, seems to be helpful for managing pain. Small studies suggest that acupuncture might improve sleep in patients with PD, but data on the effects on pain in PD is lacking. Larger, more well-controlled and reproducible studies of these therapies are needed.

Patients frequently ask about the effects of medical marijuana in managing PD, including pain symptoms. Several studies have looked at efficacy of marijuana in PD and have found that it probably is ineffective for most PD symptoms.¹¹ However, we just don’t have enough evidence to know for sure. The most rigorous study of medical marijuana in PD showed a trend toward worsening tremor.^11,12

For most people, stress and anxiety worsen tremor, and anything that relieves anxiety will improve tremor. Thus, modalities such as yoga, meditation, and mindfulness training will improve tremor. Similarly, medical marijuana may improve tremor in certain people by temporarily reducing anxiety and stress, but the evidence has not borne this out yet.

Q. Is there anything else you would like to tell our readers?

Dr. Fleisher: There are so many symptoms of PD that it can be easy to overlook pain symptoms if a patient doesn’t report them. Remember that pain may be a really prominent symptom for patients, but, given that we have only learned how pain is connected to PD in the past 20 years, patients may not be aware of the association and may not bring up pain symptoms with their neurologist.

Thus, the burden is on us to ask about pain, particularly if the patient is depressed. If a patient with PD has both pain and depression, both of those comorbidities should be targeted, because it can be hard to achieve successful outcomes for either pain or depression if one is treated without the other.

https://www.practicalpainmanagement.com/pain/other/co-morbidities/pain-parkinson-disease-spotlight-women