Useful Fitness and Informational Resources for Parkinson’s Patients

internet resources

More than 10 million people are living with Parkinson’s disease around the world. While this number seems shocking, it also means that we have a lot of people fighting for change, relief, a cure, or a solution to some of the difficulties that Parkinson’s yields. Research and interest in Parkinson’s are making connections easier, and more and more gyms are offering Parkinson’s fitness programs. Whether you’re looking for fitness resources, a good book or blog, or educational platforms, the following internet links might offer some inspiration.

Fitness resources

Exercise is healthy for everyone, but there’s evidence that it helps Parkinson’s patients manage certain symptoms of the disease. Parkinson’s specific exercise classes are popping up all across the country. How do you find a group that fits your interests? What if you don’t have access to a Rock Steady Boxing location? Or what if boxing isn’t the right fit for you?

Adaptive Training Foundation

The Adaptive Training Foundation aims to empower its participants through high-intensity athletics and community building. Its programs — Redefine, Reignite, Redeploy — help adaptive athletes push themselves to new levels of fitness, compete successfully, and challenge themselves physically. The facility is located in Texas.

PD Movement Lab (New York)

Pamela Quinn opened the first PD Movement Lab in 2006 to explore Parkinson’s through dance. A patient herself, Quinn uses her background in dance to experiment with a variety of techniques in order to help her students find solutions to mobility issues. PD Movement Lab is a New York company with branches in Manhattan and Brooklyn, but the organization is expanding its online presence to make dance accessible to anyone with Parkinson’s.

Parkinson’s Cycling Coach

There’s evidence that pedaling really fast can help reduce Parkinson’s symptoms by up to 35 percent. The people at Parkinson’s Cycling Coach aim to train people to lead indoor cycling classes, which will help patients benefit year-round. Cycling can be done at home or with a group, indoors or outdoors. And if you’re looking for a goal, Pedaling 4 Parkinson’s is an annual race that takes place in Colorado. The proceeds are donated entirely to Parkinson’s research. Having an event to train for might give you a bit of inspiration.

Informational resources

As Parkinson’s progresses, it becomes more difficult to leave the house. Physical developments make transportation tricky, and sometimes you just don’t want to be seen struggling. Resources are out there. Whether you’re seeking information or a way to exercise on your own, the internet is full of incredible platforms.

American Parkinson Disease Association

The American Parkinson Disease Association (APDA) is a grassroots organization dedicated to fighting Parkinson’s by way of fundraising, education, and public elevation. ADPA provides current news that’s related to developments in the disease and offers a location finder to help you get in touch with Parkinson’s resources near you. Its website includes information that’s tailored to specialized communities, like veterans, first responders, bilingual patients, and early-onset patients (those diagnosed before the age of 50).

Stanford Medicine

Standford Medicine, in partnership with APDA, has an incredible community outreach webpage. It includes information on local support groups and exercise classes, and offers resources like fact sheets, books, exercise videos, and live-streaming fitness classes for a wider internet audience. The “Living with PD” category touches on topics like the effect of Parkinson’s on driving ability and shares the stories of individuals’ experiences with deep brain stimulation surgery. This is a terrific resource for those who want credible information about Parkinson’s.

The right stuff

Navigating change can easily become overwhelming, and everyone’s experience with the progression of Parkinson’s is different. This can make it hard to find resources that are relevant to your situation. With a click of the mouse, however, you can access a range of information sources and fitness programs that might help you manage your disease. These websites are good places to start.

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Panic Attacks Can Go Hand-in-Hand with Parkinson’s Disease

panic attacks

Twice in the past month I have had what I am calling panic (anxiety) attacks, which are something I had never experienced before. I had shortness of breath and my heart was beating much faster than normal. Since the only activity I was involved in at the time was trying to go to sleep, it concerned me. It scared me enough that I told my husband about it the following day.

I consulted Dr. Google and here’s what I found:

A study showed that panic attacks in Parkinson’s disease could possibly be a long-term complication of levodopa therapy. The keyword here is “possibly,” which isn’t definitive enough for me, plus the study is from 1993. I skipped that one and continued my search.

Dr. Google led me to the Parkinson’s Foundation, which stated, “Anxiety is a common non-motor symptom of PD. It is important to note that anxiety is not simply a reaction to the diagnosis of Parkinson’s, but is instead a part of the disease itself, caused by changes in the brain chemistry of the brain.”

It went on to say that, “Anxiety (or panic) attacks usually start suddenly with a sense of severe physical and emotional distress. Individuals may feel as if they cannot breathe or are having a heart attack. They may feel they are experiencing a medical emergency. These episodes usually last a few minutes to an hour, particularly when associated with ‘off’ periods, though they can last for longer periods of time.” 

Several different sources agree that some of the symptoms of a panic attack can be trouble sleeping, heart palpitations, hyperventilating, uncontrollable worry, chest pain, dizziness, tunnel vision, and hot or cold flashes.

Bingo. They hit that nail on the head.

The list goes on and it can be hard to diagnose what is happening, as the symptoms mimic other possibilities of what could be going on. 

When I identified what I believed to be the culprit (a panic attack), I made a note to bring it up at my upcoming appointment with my neurologist. Until then, I decided to rely on the hope and faith I had within me. I forced myself to breathe normally and drew deep upon that faith. The attack finally subsided and I was able to quit worrying about getting the porch fixed and the gate repaired and the shower installed and the sink replaced and …

Here I go again … 

This time I’m diving deep into that faith before the panic kicks in. 

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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IL-17A Accelerates Brain Inflammation and Degeneration in Animal Models of Parkinson’s, Study Finds

Parkinson's and IL-17A

Interleukin-17A (IL-17A) — a molecule that is involved in immune and inflammatory responses — accelerates brain inflammation and degeneration in animal models of Parkinson’s disease, a study has found.

The research, “IL-17A exacerbates neuroinflammation and neurodegeneration by activating microglia in rodent models of Parkinson’s disease,” was published in Brain, Behavior and Immunity.

Parkinson’s disease is characterized by the gradual loss of dopaminergic neurons in the substantia nigra — a region of the brain responsible for movement control — together with brain inflammation caused by the over-activation of microglia, which are cells that support and protect neuronal cells, and are more reactive and proliferative than neurons.

“Our recent results show that Th17 cells contribute to PD [Parkinson’s disease] neuroinflammation and neurodegeneration. In revealing the mechanism by which Th17 cells injure dopaminergic neurons, we found that Th17 cells directly contact and kill neuronal cells by an interaction between two adhesion molecules expressed on membrane of these cells,” the investigators explained.

“Nevertheless, it needs clarification whether IL-17A … can directly damage dopaminergic neurons,” they added.

Of note, Th17 are the subtype of T-cells that produces IL-17 and have been associated with several inflammatory processes; a cytokine is a molecule that mediates and regulates immune and inflammatory responses.

In this study, a group of researchers from Nantong University in China set out to investigate how IL-17A might contribute to the development and progression of Parkinson’s in two different animal models of disease.

To trigger the onset of Parkinson’s, researchers treated mice with MPTP, a neurotoxin that induces brain inflammation, loss of dopaminergic neurons, and motor impairments, as seen in patients with the disease.

In parallel, rats were treated with MPP+, another neurotoxin closely related to MPTP, that also induces the onset of symptoms similar to those experienced by patients with Parkinson’s disease.

Results showed that treatment with both neurotoxins led to a disruption of the blood-brain barrier (BBB, a semipermeable membrane that isolates the brain from the blood that circulates in the body) and to a significant increase in the levels of IL-17A in the substantia nigra of both animal models.

To examine if BBB disruption in response to neurotoxins was sufficient to allow immune cells to enter into the animals’ brains, researchers injected them with T-effector cells that had been activated in a lab dish and measured their level of penetrance into the brain.

Of note, T-effector cells are T-cells that are immediately prepared to fight a pathogen because they have a “memory” of previously encountering it; these cells also include the Th17 subgroup.

Findings revealed that when injected into animals that had been treated with neurotoxins, T-effector cells were able to travel and enter into the animals’ brains. However, when injected into healthy animals that had never been treated with neurotoxins, T-effector cells failed to infiltrate the brain.

In addition, researchers found that when T-effector cells infiltrated the brain, they worsened animals’ symptoms; dopaminergic neurons were destroyed faster, microglia became over-activated faster and motor impairments were more severe.

Conversely, when researchers blocked the activity of IL-17A in rats’ brains (by injecting an anti-IL-17A antibody) they found that all Parkinson-like symptoms the animals experienced were significantly reduced. Likewise, when they performed a similar analysis in mice that had been genetically modified to lack IL-17A, they found that neuron degeneration, microglia activation and motor deficits were decreased greatly.

Additional in vitro experiments revealed that IL-17A had a direct impact on microglia activation, but not on neuron survival. According to the team, IL-17A requires the presence of microglia to accelerate neuronal loss.

Moreover, they discovered this effect was stronger in the presence of tumor necrosis factor alpha (TNF-a), a signaling molecule involved in immune and inflammatory responses, produced and released by activated microglia.

“[These] findings suggest that IL-17A accelerates neurodegeneration in PD [by inducing the] activation [of microglia] and at least partly [by promoting the release of other pro-inflammatory molecules, such as TNF-a],” the researchers wrote.

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Alpha-Synuclein Protein Works to Repair Damage to Cell’s DNA, Study Suggests

alpha-synuclein and DNA repair

Contrary to current knowledge, alpha-synuclein protein — whose toxic form is responsible for the formation of Lewy bodies — may play a crucial role in preventing cell death by repairing damaged DNA, a study has found.

This critical function of the protein may also be lost in Parkinson’s patients, its researchers said.

The study, “Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders,” was published in Scientific Reports.

Parkinson’s is marked by a buildup in the brain of the alpha-synuclein protein, which forms clumps known as Lewy bodies that damage and kill neurons (nerve cells). These protein inclusions are found in the cell’s cytoplasm — the jelly-like fluid that fills a cell.

Although it remains unclear how cytoplasmic aggregation of alpha-synuclein into Lewy bodies contributes to neuronal death, alpha-synuclein has also been found in the cell’s nucleus, where DNA is located and where important DNA repair mechanisms take place.

Researchers at the Oregon Health & Science University had previously shown that the formation of Lewy bodies coincided with the loss of soluble alpha-synuclein from both the cytoplasm and nucleus of mouse neurons with aggregates (clumps) in them.

“This suggests that cytoplasmic alpha-synuclein aggregation may decrease the amount of protein available for any nuclear or cytoplasmic role it may play,” the researchers wrote.

The same team now investigated whether alpha-synuclein could be involved in the DNA damage response.

Alpha-synuclein was found in the same cellular sites as DNA damage response components in both human and mouse brain cells.

DNA damage was then chemically induced in human cells that lacked alpha-synuclein. Researchers reported finding higher rates of DNA damage (what they called “double-strand breaks”) compared to alpha-synuclein-bearing cells. Likewise, mice without alpha-synuclein had increased neuronal DNA damage, which was rescued by reintroducing the human form of alpha-synuclein.

Importantly, mouse and human neurons with Lewy bodies had increased levels of DNA damage.

Scientists also observed that normal (i.e., non-toxic) alpha-synuclein is rapidly recruited to DNA damage sites and helps to repair harm by binding to the DNA molecule and facilitating a repairing reaction; more specifically, this process is called the non-homologous end-joining reaction.

Besides its known toxic role in Parkinson’s, findings suggest alpha-synuclein may have an important function in the cell nucleus, that of regulating DNA repair. They also suggest that such function is compromised in Lewy inclusion-bearing neurons, which, in turn, contributes to cell death.

“This is the first time that anyone has discovered one of its [alpha-synuclein’s] functions is DNA repair,” Vivek Unni, MD, PhD, an associate professor of neurology in the OHSU School of Medicine and senior author of the study, said in a news release.

“That’s critical for cell survival, and it appears to be a function that’s lost in Parkinson’s disease,” Unni added.

“Based on these data, we propose a model whereby cytoplasmic aggregation of alpha-synuclein reduces its nuclear levels, increases DSBs [double-strand breaks], and may contribute to programmed cell death via nuclear loss-of-function. This model could inform development of new treatments for Lewy body disorders by targeting alpha-synuclein-mediated DNA repair mechanisms,” the team concluded.

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Inflammatory Molecules in Blood May Help Predict Parkinson’s Progression, Study Suggests

machine learning, cytokines

Inflammatory molecules called cytokines may be a peripheral biomarker of Parkinson’s progression, especially of its characteristic changes in motor abilities, according to new research using machine learning.

The study, “Parkinson’s progression prediction using machine learning and serum cytokines,” appeared in the journal npj Parkinson’s Disease.

Besides altered immune responses and distinct populations of immune cells, increased levels of cytokines — small proteins secreted by cells of the immune system — may link inflammation with Parkinson’s. This has been seen in asymptomatic carriers of the G2019S mutation in the LRRK2 gene, which accounts for 1–5% of all Parkinson’s cases. Still, the extent to which peripheral cytokines may trigger the disease remains unclear.

Increasing evidence suggests that Parkinson’s may start in the periphery (for example, in the gut), possibly enabling the identification of markers of disease progression that could improve outcomes for patients and lead to better trial design.

Researchers at The University of Sydney, Australia, used machine learning to further assess the correlation between peripheral inflammatory cytokines and Parkinson’s symptoms. They analyzed serum samples from 160 patients (mean age 68–69, ages 57–58 at diagnosis), 80 of whom (40 men) had the G2019S mutation and 80 who did not (54 men), all followed within the Michael J Fox Foundation Parkinson’s Progression Markers Initiative. They then used machine learning models to predict clinical outcomes at two years.

Comparing the two groups, patients who carried the G2019S mutation had milder motor disease and less severe hyposmia — a reduced sense of smell — as assessed with the Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III) and the University of Pennsylvania smell identification test. At baseline (study start), mutation carriers also had higher levels of the cytokines PDGF and MCP1 than those in the group of idiopathic (of unknown cause) Parkinson’s disease.

One year later, the scientists assessed blood serum samples from 126 of these patients. Results revealed that two cytokines, GCSF and interleukin (IL)-5, had the greatest variation. However, only the levels of one cytokine, IL-1RA, differed between the two groups.

Clinically, the patients showed more severe motor symptoms and depression, which were associated with a significantly decreased (worse) score in the Schwab and England activities of daily living (ADL) scale.

A subsequent analysis showed that, among a subset of 76 patients, higher baseline levels of 14 cytokines correlated with greater (worse) findings on the geriatric depression scale over two years. A similar link was found between seven cytokines and motor function. IL-5 and GCSF were among the cytokines whose levels correlated with both scales.

Using machine learning, researchers observed that two cytokines, MIP1 alpha and MCP1, made the biggest peripheral contribution to predicting motor symptom severity using the Hoehn and Yahr and UPDRS III scales, respectively.

As such, higher levels of these molecules were associated with faster motor deterioration.

In turn, the cytokines IL-6 and IL-4 were the primary contributors to predicting geriatric depression. All top cytokine contributors were also good predictors of the Schwab and England ADL scale scores.

Using cytokines improved predictions by 20% over clinical data alone. As for other analyzed variables, age and gender were among the top 10 contributors to predicting ADL and UPDRS-III scores, respectively.

“These results provide information on the longitudinal assessment of peripheral inflammatory cytokines in [Parkinson’s] and give evidence that peripheral cytokines may have utility for aiding prediction of [Parkinson’s] progression,” the scientists wrote.

Future studies should use a larger and more diverse group of patients, and assess the potential impact of medications on both clinical outcomes and cytokines levels, the researchers added.

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Depression and Psychosis Are Markers of More Severe Disease, Database Study Says

mental illness and Parkinson's

Mental illness in people with Parkinson’s disease, more frequently found in female and older patients, appears to associate with more severe disease, a new study reports.

Titled, “Comorbid Depression and Psychosis in Parkinson’s Disease: A Report of 62,783 Hospitalizations in the United States,” the study was published in the journal Cureus.

Although Parkinson’s disease is best known for its motor symptoms, non-motor symptoms can play an impactful role too. Depression and psychosis (difficulty discerning what’s real and what isn’t) are both psychiatric disturbances known to occur in Parkinson’s patients, and these conditions can, understandably, seriously impact their quality of life.

Researchers across the U.S. set out to examine the interplay between these mental illnesses in Parkinson’s and disease severity, patient demographics, and hospital outcomes.

They analyzed data from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) covering 2010–14; this included information on 62,783 people with Parkinson’s, of whom 11,358 (18.1%) were diagnosed with depression and 2,475 (3.9%) experienced psychosis.

Both mental health conditions were significantly more common in female patients; women made up 37.2% of the total population, but 44.9% of those with depression and 41.8% of those with psychosis.

Depression was more common among white patients (84.9% with depression were white, compared to 80.6% white in the total population), whereas a disproportionate percentage of people with psychosis were black (8.7% vs. 6.5% of total population) and were in the lowest quartile of household income (28.6% vs. 22.4% in the total population).

Older patients were also more likely to experience mental illness, with those older than 80 years at a 5.3-fold greater risk than patients in their 40s and 50s.

Having psychosis was associated with more severe disease: 78.8% of Parkinson’s patients with psychosis had moderate or severe disease compared to 66.2% of the total population, meaning patients with psychosis were 1.38 times more likely to have more severe disease. In those with depression, 67.9% had moderate or severe disease, a similar rate as seen in the total population.

Additionally, around a quarter of the total population received deep brain stimulation (DBS) as part of their treatment. A similar proportion of patients with depression were given DBS, but only 3.9% of patients with psychosis did.

Patients with psychosis also tended to have longer average hospital stays (7.3 vs. 4.1 days in the psychosis and total cohorts, respectively), but, interestingly, lower average total hospital charges ($31,240 vs. $39,688 in the total cohort). Both average length of hospital stay and average costs were similar for the total population and those with depression.

These results are all only associations; the study was not designed to find cause-and-effect relationships, and regardless, such relationships are likely affected by the combination of many factors. More research will be needed to better understand the interplay between these factors, but this work does highlight the impact of mental health in Parkinson’s disease.

“The results of our study suggest that healthcare providers should actively screen for psychiatric comorbidities like depression and psychosis in patients with PD [Parkinson’s disease],” the researchers concluded, adding, “[p]sychiatric comorbidities in PD should be considered an integral part of the disease, and a multidisciplinary approach to managing this disease is crucial to improve the overall outcome and the health-related quality of life of PD patients.”

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Exercising with Parkinson’s Disease: Try It and See the Benefits

panic attacks

I began taking Rock Steady Boxing classes about nine months ago. The exercise program is tailored for those with Parkinson’s disease, and if you’re like me, you’ve dragged your feet and refused to go for any number of reasons or excuses. Maybe there isn’t a class near you. Or perhaps you feel too tired and don’t think you’ll have enough energy to do what’s required. Maybe money or time is the issue.

Do me a favor. 

Just consider it

I was reluctant to go. Mostly because I’m an introvert — yes, I really am. I have to push myself to get out there. And so I did. I forced myself to check it out almost nine months ago, and I am still going. 

I recently read a discussion in a Parkinson’s Facebook group I belong to. Someone asked what decision others had made in their lives since their diagnosis that had made the most positive difference to their health. I was surprised by the number of answers about exercise. It seems logical to me now, but before attending boxing classes, I may have had a different response, such as increasing my chocolate intake.

We are meant to be active

A 2018 study looked at the reduction of movement in neurological diseases. Commenting on the research, one of its authors, Dr. Raffaella Adami, told the journal Frontiers that we are meant to “walk, run, crouch to sit, and use our leg muscles to lift things.”

According to the article, “Cutting back on exercise makes it difficult for the body to produce new nerve cells — some of the very building blocks that allow us to handle stress and adapt to challenge in our lives.”

When I joined my boxing class, I was surprised by the number and variety of exercises we had to do. I had figured that activities would be specifically related to boxing. We spend the first half of the class on exercises such as jumping jacks, squats, leg raises, jump-rope, stair steps, balance beam, ladder steps, box steps, pushups, lunges, planks, and various activities using punching bags, jelly bags, and speed bags. Then we practice punches with our coaches. We close out our session with a game or competition — my favorite part.

Many participants in the Facebook group discussion agreed that their decision to join a Rock Steady Boxing class had been beneficial. The next two most popular activities were walking and yoga. I don’t think that it matters which form of exercise you choose as long as you are doing something.

See the benefits

May I encourage you to start an exercise routine if you haven’t already. You’ll soon realize that you can do more than you could before, and you may find that your overall well-being has improved.

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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CHMP Favors EU Approval of Inbrija to Treat Parkinson’s Off Periods

CHMP recommendation

The Committee for Medicinal Products for Human Use (CHMP) — an arm of the European Medicines Agency (EMA) — is recommending that Inbrija, by Acorda Therapeutics, be approved to treat off periods in Parkinson’s patients on a carbidopa/levodopa regimen.

The European Commission will review CHMP’s positive opinion, with a decision expected before year’s end.

“We are delighted that Inbrija has achieved this important milestone, and look forward to the EC’s final decision later this year. There are approximately 1.2 million people in the EU living with Parkinson’s. We estimate that 40% of these individuals experience off periods, which are considered extremely disruptive,” Ron Cohen, MD, president and CEO of Acorda, said in a press release.

Inbrija is a self-administered, inhaled formulation of levodopa developed to treat off episodes. These periods, when levopoda wears off before a new dose can be taken, are characterized by the re-emergence of Parkinson’s motor symptoms, and are typically more common as the disease progresses.

Inbrija delivers a precise dose of levodopa to patients’ brains that, because it is inhaled, bypasses the need to be absorbed in the digestive system. As such, it can deliver a higher and more consistent levodopa dose to the brain.

Inbrija is approved by the U.S. Food and Drug Administration (FDA) to treat Parkinson’s symptoms during off episodes. 

CHMP’s decision was based on clinical data from the Phase 3 SPAN-PD clinical trial (NCT02240030). The study evaluated the safety and effectiveness of two doses of Inbrija — 84 mg and 60 mg — or a placebo taken up to five times a day in 351 Parkinson’s patients experiencing off periods. Treatment was maintained for 12 weeks.

Results showed that Inbrija significantly improved patients’ motor function compared to placebo. Researchers found no safety concerns. The most common adverse events were cough, upper respiratory tract infection, and throat irritation.

Trial outcomes were published in The Lancet Neurology, in the study “Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled phase 3 trial.”

Inbrija was also studied in two long-term Phase 3 trials — the CVT-301-005 trial (NCT02352363) and the CVT-301-004E study (NCT02242487) – that evaluated Inbrija used up to five times daily for 12 months.

Researchers found no changes in treated patients’ lung function compared with standard levodopa treatment, supporting Inbrija’s safety as an off-period medication.

Efficacy data from the CVT-301-005 trial also confirmed that Inbrija eases problems with motor function that emerge in off periods. Treatment was found to enable symptom control within 60 minutes of the dose and lowered the length of patients’ off times.

Acorda’s European application covers all European Union countries, as well as Norway, Liechtenstein, and Iceland.

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Boosting Levels of Molecule in Brain Slows Parkinson’s Progression and Eases Symptoms, Animal Study Finds

animal model study

A molecule called GM1 ganglioside may protect the brain against the molecular changes associated with Parkinson’s disease progression, and may one day directly treat its neurodegenerative processes, according to an early study.

The study, “GM1 Ganglioside Modifies α-Synuclein Toxicity and is Neuroprotective in a Rat α-Synuclein Model of Parkinson’s Disease,” was published in Scientific Reports.

GM1 ganglioside is a component of the cell membrane and has long been considered a master modulator of the nervous system because of the many functions it regulates.

Parkinson’s patients have lower-than-usual levels of GM1 ganglioside within the substantia nigra, a brain region that’s severely damaged in Parkinson’s.

In lab experiments, GM1 ganglioside was found to protect against the aggregation of alpha-synuclein protein, the main component of Parkinson’s hallmark Lewy bodies. Specifically, GM1 ganglioside did not allow acetylated alpha-synuclein to form harmful clumps or aggregates within the cells. Acetylated (with an added acetyl group) alpha-synuclein has been shown to more effectively induce intracellular clustering in nerve cells, compared to the unchanged form of alpha-synuclein.

This suggests that problems with GM1 may somehow contribute to the vulnerability and degeneration of dopamine-producing neurons seen in Parkinson’s disease.

Using a rat model of Parkinson’s, researchers for this study investigated the extent to which GM1 ganglioside could protect against alpha-synuclein toxicity and the development of Parkinson’s-related molecular and behavioral changes.

A single injection of an adeno-associated viral vector (AAV) carrying a copy of human mutant alpha-synuclein was administered into the substantia nigra of rats, leading to protein aggregation and the degeneration of dopaminergic neurons, a decrease in dopamine levels within the striatum (another motor control brain center that’s affected by Parkinson’s), and behavioral problems.

Some rats were then randomly assigned to daily GM1 ganglioside injections (30 mg/kg) beginning 24 hours after AAV-alpha-synuclein administration and lasting for six weeks (early start group). Others were given the daily GM1 ganglioside injections (30 mg/kg) three weeks after the AAV-alpha-synuclein, and lasting for five weeks (delayed start group).

Results showed that GM1 ganglioside protected against loss of substantia nigra dopamine-releasing neurons and striatal dopamine levels, and reduced alpha-synuclein clumping. Importantly, the delayed start of GM1 ganglioside reversed motor deficits that had appeared in this animal group, suggesting the therapy was able to restore their motor function.

“When we looked in the brains of these animals, not only did we find we could partially protect their dopamine neurons from the toxic effects of alpha synuclein accumulation, we had some evidence that these animals had smaller and fewer aggregates of alpha-synuclein than animals that received saline injection instead of GM1,” Jay Schneider, PhD, a professor in the department of pathology, anatomy and cell biology at Thomas Jefferson University and first author of the study, said in a press release.

Scientists believe the low brain levels of GM1 ganglioside seen in Parkinson’s may facilitate the formation of harmful alpha-synuclein clumps.

“By increasing GM1 levels in the brains of these patients, it would make sense that we could potentially provide a slowing of that pathological process and a slowing of the disease progression, which is what we found previously in a clinical trial of GM1 in Parkinson’s disease patients,” Schneider said. Results of that university-sponsored trial (NCT00037830) in 77 patients, concluded in 2010, supported its potential as a disease-modifying treatment.

Schneider’s team is now focused on finding out what other effects GM1 ganglioside might have on alpha-synuclein.

“It’s important to understand how GM1 is working because there might be other ways we could manipulate GM1 levels in the brain to have a beneficial effect,” he added.

According to the researchers, GM1 has the potential to be a treatment that directly impacts “the underlying disease processes in [Parkinson’s disease] and that can slow neuronal cell death and symptom progression,” protecting dopamine neurons from dying “as well as rescue and restore function to damaged but viable neurons.”

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Managing Chronic Pain, Part 1: Understanding a Shift in Perspective

Dr. C

Pain and suffering are not the same. An internet search for “difference between pain and suffering” yields dozens of sites for writers and practitioners, like Ashley Pennewill and Ann Marie Gaudon, who extol the benefits to be gained from this conceptualization. The repeated message is that pain is the physical experience connected to insult and injury, while suffering is the “story” we tell ourselves about the pain experience. Our total pain experience is the sum of physical pain and suffering, with each affecting the other.

Shifting my perspective on chronic pain to one that understands the role of suffering in the total pain experience has helped me to better manage my chronic pain (including discontinuing opioid treatment), decrease the occurrence of dysregulated emotions, and achieve an overall improvement in well-being.

The difference between pain and suffering is an encyclopedic topic that has been the focus of writings since at least the time of the Buddha. A focus on the mind-body link examines how we can use that information to reduce suffering so that we can better manage chronic pain.

The mind/body link as an attention-to-stimulus process was partially described in my column on irritability. The process of pain stimulus creates the need for attention to the stimulus. The feelings and thoughts associated with the stimulus escalate. It is a feedback loop that helps us in the face of danger, but as the feedback cycles out of control, emotions often become unregulated and out of control. The spiraling loop can become a barrier to well-being. The experience of emotion dysregulation (see figure) is one link between the pain, feedback, attention processes, and suffering.

(Graphic by Dr. C)

The figure illustrates emotion dysregulation as an experience connected to exceeding one’s emotion dysregulation threshold (EDT) due to increasing emotional intensity over time (dysregulation delay, or DD). Once the threshold is crossed, we experience emotional dysregulation (EDE). This is followed by a cooling of the emotion intensity (CD). The goal is to reduce the intensity and duration of the emotional dysregulation. This is where the shift in perception is applied.

It is a shift from feeling like we can’t do anything to keep our emotions from getting out of control to an understanding and belief that we can change the escalation. It is adopting the perception that we have some control over this dysregulation and that, given the nature of neural plasticity, there is the possibility of reducing the intensity of dysregulation experiences and lengthening dysregulation delay times. This success can lead to less suffering and make it easier to manage chronic pain.

Pain is reported by many Parkinson’s patients. “Among the different forms of PD-related pain, musculoskeletal pain is the most common form, accounting for 40%–90% of reported pain in PD patients,” according to a paper by Orjan Skogar and Johan Lokk.

“Individuals with Parkinson disease (PD) frequently suffer from pain that interferes with their quality of life but may remain under-recognized and inadequately treated,” reports Neurology Times, citing a study published in the Journal of Neurology. I am one of these individuals. I have good days and very bad days — the ugly days.

The Neurology Times article continues, “’We found pain to be highly frequent, quality of life-impairing but insufficiently and unsystematically treated,’ wrote first author Carsten Buhmann, MD, of the University Medical Center, Hamburg-Eppendorf (Hamburg, Germany) and colleagues.”

When we live with Parkinson’s and experience pain, we are not alone. The Parkinson’s Foundation says, “Chronic pain is twice as common among people with PD as it is in people without it. In fact, more than 80 percent of people with PD report experiencing pain and say it’s their most troubling non-motor symptom.”

I am in pain most of the time. I cross the threshold when I am having difficulty managing the pain and the connected feedback loop. If I add some additional stressor — emotional, physical, or situational — that feeds the emotional turmoil, and I cross the threshold sooner. Accepting that I can do something about it (and have the skills) is the shift in perspective. It is a shift from being a servant to the whims of my emotions and their consequences to presenting as a calm, centered being who seeks continued progress on his wellness map.

I am still learning and practicing techniques to help me shift my perspective so that I can manage my chronic pain more successfully. I will discuss some of these techniques in Part 2 of this series. Attempts to change human practices are only as effective as the intent behind them. The shift in perspective allows us to firmly establish this proper intent.

What are your thoughts about emotion dysregulation and human suffering? Please share in the comments below.

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