Loud, Startling Sounds Can Decrease Parkinson’s Muscle Stiffness, Study Suggests

loud sounds, muscle stiffness

Loud and alarming sounds can reduce muscle stiffness in Parkinson’s disease patients treated with subthalamic nucleus deep brain stimulation (STN-DBS), a study suggests.

The study, “Influence of alarming auditory cues on viscoelastic stiffness of skeletal muscles in patients with Parkinson’s disease,” was published in Clinical Biomechanics.

Almost 100 years ago, a French neurologist described a phenomenon called paradoxical kinesis (meaning “difficult to understand movement”) consisting of a dramatic but temporary reversal of Parkinson’s motor symptoms in the face of startling situations such as an oncoming car or loud sounds.

“The phenomenon of [paradoxical kinesis] suggests the existence of neural systems that can override parkinsonian impairment in certain conditions,” the researchers wrote in this study.

The association between paradoxical kinesis and muscular rigidity has never been described, probably due to the subjective, observer-dependent scoring methodology while performing clinical assessments of “rigidity during the transitory motor alterations” and also due to the “subjective nature of the examinations according to the Unified Parkinson’s Disease Rating Scale (UPDRS),” according to the researchers.

Increased rigidity has been linked to more viscoelastic stiffness of skeletal muscles. Muscles behave like springs, and while something that is elastic immediately returns to its original shape once a stress has been removed, a tissue that is viscous will deform permanently. Therefore, viscoelasticity refers to the muscle having properties of both, allowing it to slowly recover from being stretched or deformed.

Measurement of muscle tone using a myotonometer — a device that measures viscoelastic characteristics of soft tissues — has proved useful in quantifying the effect of therapeutic interventions on rigidity in Parkinson’s patients.

“Thus, evaluation of viscoelastic stiffness could potentially enable quick and reliable measurements of muscular rigidity during the enhancement of motor performance due to external cues in patients with [Parkinson’s disease],” the researchers wrote.

The team from the University of Tartu in Estonia assessed the effect of alarming auditory signals on viscoelastic stiffness of skeletal muscles in patients treated with STN-DBS — a surgical treatment for Parkinson’s disease that involves implanting a device to stimulate targeted regions of the brain with electrical impulses generated by a battery-operated neurostimulator. Patients can use a handheld controller to turn the DBS system on and off.

The team recruited 10 advanced stage Parkinson’s disease patients (three women and seven men) who had been treated with STN-DBS for approximately 4.5 years prior to the study.

Eight subjects had akinetic-rigid (i.e., slowness of movement accompanied by muscle stiffness), and two had the tremor-dominant subtype of Parkinson’s disease. Ten age- and gender-matched healthy individuals were also recruited to use as controls.

Using a myotonometer, the investigators measured the viscoelastic stiffness of the participants’ wrist skeletal muscles, or in other words, the muscle’s resistance to the force that changes its shape, after one night of Parkinson’s medication withdrawal.

Wrist examinations were performed by two different examiners, 10 times each. Measurements were repeated and compared during the DBS-on and DBS-off periods, with and without auditory alarming signals.

Compared with the DBS-off period, muscular stiffness was significantly reduced in the DBS-on phase, supporting the the effectiveness of the stimulation treatment in lessening one of Parkinson’s motor features.

In addition, wrist stiffness was also significantly decreased during the DBS-off period in the presence of alarming auditory signals.

“The mean values of stiffness during the DBS-on phase were lower than during the DBS-off with [alarming auditory] signals phase but the difference was not significant,” the researchers wrote.

Exposure to loud sounds did not change muscle stiffness in the control sample, suggesting that the paradoxical kinesis phenomenon is more pronounced in Parkinson’s patients.

“According to our data, the changes in muscular rigidity due to [alarming auditory] signals are an exclusive characteristic of the patients with [Parkinson’s disease],” the researchers said.

Further larger-scale research is necessary to confirm this study’s findings and assess the efficacy of auditory cueing in Parkinson’s disease.

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Treadmill Incline Training Improves Walking Speed of Parkinson’s Patients, Study Finds

treadmill incline training

Eight weeks of training on a treadmill with continuously varying surface inclines improved gait disturbances, particularly walking speed, in Parkinson’s disease patients, researchers report.

Their finding were published in the study, “Exploring gait adaptations to perturbed and conventional treadmill training in Parkinson’s disease: Time-course, sustainability, and transfer,” in the journal Human Movement Science.

As the disease progresses, Parkinson’s patients experience an increase in gait difficulties and balance problems, lowering their mobility and quality of life.

In addition, studies have shown that Parkinson’s patients take shorter and slower steps, and have high stride-to-stride variability.

Because some gait disturbances are drug-resistant, nonpharmacological treatment options are needed to improve these patients’ quality of life.

“Improved stride length and stride-to-stride variability have been demonstrated following several weeks of treadmill practice for both, overground and treadmill walking, respectively,” the authors wrote.

Researchers had recently demonstrated that eight weeks of treadmill therapy with additional postural perturbations (i.e., varying surface inclines) improved overground gait speed and dynamic balance control in Parkinson’s patients.

Now the same team at Friedrich-Alexander University Erlangen-Nürnberg has analyzed spatiotemporal gait adaptations to treadmill training — with and without an incline — both on and off the machine.

They used data from a randomized controlled Phase 1 trial (NCT01856244) aimed at investigating the effectiveness of a sensorimotor treadmill intervention to improve walking and balance abilities in people in the early stages of Parkinson’s disease.

Sensorimotor treadmill training was conducted on a special machine that challenged the participants through small oscillations, simulating walking on natural, uneven surfaces. This intervention was compared with conventional treadmill training without surface perturbations.

Thirty-eight Parkinson’s patients were randomly assigned to 40 minutes of treadmill training two times per week for eight weeks. Of these patients, 18 performed treadmill training with continuously varying surface inclines, while the other 20 walked on the treadmill without surface perturbations.

Patients were assessed every week during training protocol (prior to the training sessions), within one week after the intervention, and at a three-month follow-up.

Gait variability significantly decreased in both training groups. Nonetheless, longer stride length and time, stance time, and swing time were significantly improved only in the treadmill incline training group.

For reference, one gait cycle consists of two phases: stance, or the period of time that the foot is on the ground, and swing, meaning the period of time that the foot is off the ground moving forward.

Researchers then investigated the sustainability of gait changes over three months.

At the three-month follow-up, there were significant changes between the groups in stance and swing time, which were due to a much higher variability in the conventional treadmill training group. Statistical comparisons within the groups revealed no significant changes in the treadmill incline training group.

Additional statistical analysis also showed decreased step length asymmetry in the conventional treadmill training group.

The team then assessed the extent of transfer effects to overground gait in both training regimes.

“When considering the entire sample, significant changes in overground gait parameters at [week 8] were observed only for stance- and swing time, with a significantly decreased stance time … and a corresponding increase in swing time,” they wrote. However, these findings were statistically significant only in the treadmill incline training regime.

“[Parkinson’s disease] patients demonstrated marked gait adaptations to the eight-week treadmill intervention, which were partially retained after three months follow-up,” they noted.

Treadmill training with small oscillations seemed to reduce gait disturbances, but the transfer of such changes to overground walking was limited in most evaluated variables.

Further research is still necessary to corroborate these findings.

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Intimacy Can Be Challenging with Parkinson’s Disease

intimacy

Sherri Journeying Through

The other day, my husband told me he felt alone. Then he said he felt distanced. How could that be? We are together almost every day, 24/7. But being together and being together are very different, especially when it comes to having Parkinson’s disease.

This disease has many symptoms, of which tremor is the most prominent. Other symptoms are not often discussed, particularly depression. Another that I will discuss in this column is intimacy difficulty. 

Most people with Parkinson’s are aware that intimacy can be an issue for many reasons. One may be an unintentional lack of interest the person with PD may not even be aware of. Another may be pain or discomfort. Yet another may be the inability to “perform.” Any of these reasons can disrupt the relationship, sending messages of rejection or appearing to indicate the partner is undesirable and even unloved. 

First, let me say that, whether you’re the person with PD or the partner, you are not alone. I, too, struggle with this subject for many reasons. I can feel inadequate in many ways, but I didn’t realize I was inadvertently making my husband feel distanced and alone until the other day when we had a heart-to-heart talk.

According to the American Parkinson Disease Foundation, “From lack of sexual desire to low libido to difficulties with orgasmic functioning, this chronic, progressive, neurological disease can impair your sexuality in one way or the other.” The Michael J. Fox Foundation adds that “as many as 70 to 80 percent of those with PD experience sexual dysfunction.”

Dealing with bradykinesia, or slowness of movement, and rigidity can become an issue in a relationship. Symptoms such as tremors and dyskinesia also can contribute to dysfunction and leave one or both partners feeling inadequate.

This also plays out in everyday signs of affection such as hugging, kissing, or holding hands. The person with Parkinson’s can appear aloof to the need for affection and leave a partner feeling more distanced with each day. Before long, both are wondering why the other has stopped finding them attractive and don’t want to be with them sexually anymore. I can’t help but believe that the sad stories I have heard about spouses who have left their partners with Parkinson’s disease are more likely due to a lack of communication than just having the disease.

It’s hard to overcome feelings of inadequacy when they are kept bottled up and aren’t talked about. The first person to talk to about how you’re feeling is your partner or spouse. A frank and honest discussion about the effects of Parkinson’s on intimacy and how to overcome it in everyday life is critical. It might mean an intentional hug in the morning or time set aside only for conversation. (This does not include talking while watching the television.)

Speaking of television, the other day, I was watching a show and at the end, a man proposed to his girlfriend. Of course, she said yes — it was a Hallmark movie, after all. Then the guy said, “I hope the magic never fades.” 

None of us wants the magic to fade, especially if we have Parkinson’s. It’s taken so much already. We need to keep communicating with each other, no matter how hard it may be at times. It’s those times that bind us together more tightly, and the tighter we hold each other, the greater the magic will be. 

***

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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Monitoring with PKG System Helps Change Care in Nearly a Third of Parkinson’s Cases, Real-World Study Reports

PKG recording system

Continuous monitoring of movement symptoms using a wearable device called the Personal KinetiGraph (PKG) may help clinicians make more appropriate treatment choices for their patients with Parkinson’s disease, according to a real-world clinical study.

The study, “Qualitative Evaluation of the Personal KinetiGraphTM Movement Recording System in a Parkinson’s Clinic,” was published at the Journal of Parkinson’s Disease.

Parkinson’s is a progressive disease characterized by the degeneration of dopamine-producing neurons, causing several motor symptoms such as bradykinesia — slowness of movement — muscular rigidity, and tremor.

Although Parkinson’s can cause a range of non-motor symptoms, such as sleep problems, constipation, slurred speech, and mood disorders, management of the disease is mainly focused on reducing the burden of motor symptoms. To do so, clinicians must rely on patients’ reports and one-time clinical assessments to find the most appropriate treatment strategy as well as to make therapy adjustments.

The development of wearable sensors represents a new opportunity to help clinicians more accurately evaluate Parkinson’s patients’ movement patterns.

“New wearable sensors have the advantage of offering continuous objective measurement of patient movement during regular activities of daily living,” the researchers wrote. “[They] have the potential to provide important additional information in a more accurate way to augment day to day clinical care of Parkinson’s patients.”

The PKG system, developed by Global Kinetics Corporation, is a wristwatch-like device worn on the side of the body that is most affected by the disease and continuously collects patients’ movement data — such as tremor, slow or involuntary movements, motor-skills fluctuations, and immobility — providing information to the patient’s doctor.

The PKG system is now commercialized for clinical use in 17 countries, including the U.S. and several European countries. Global Kinetics recently announced that its PKG-Watch was recommended by two separate expert panels to improve clinical management of Parkinson’s disease.

Researchers at the Parkinson’s Institute and Clinical Center in California have now evaluated the impact of using continuous objective movement measurement with the PKG system in the routine clinical care of Parkinson’s patients. The Parkinson’s Institute began using the PKG system in December 2015 as an additional evaluation method on top of clinical visit history and examination.

“The wearable PKG technology provides objective measurements which allow us to further deliver the highly individualized care that a patient deserves,” Carrolee Barlow, MD, PhD, former CEO of the Parkinson’s Institute and Clinical Center and senior author of the study, said in a press release.

In routine care, physicians targeted PKG use to patients they believed could benefit from objective movement measurement — mainly those who were new to the clinic; were experiencing clear symptom fluctuations; were unable to clearly report their symptoms; and were considering or using deep brain stimulation or Duopa (carbidopa/levodopa, marketed by AbbVie).

Between December 2015 and July 2016, 89 patients with Parkinson’s disease were selected to use the PKG system as part of their routine clinical evaluation and follow-up, 81 of whom were included in the final analysis. Forty-five patients had one PKG, and 44 had two PKGs, 10 of whom went on to have three PKGs completed.

Physicians provided their collective views on the impact of the system on patient care in a total of 112 surveys. Of these, 41% indicated that the PKG provided additional information to the physician. However, 59% reported that the system failed to provide additional information.

Of the surveys reporting that the PKG did provide additional information, 78% indicated the data provided by the PKG system resulted in changes in patient care, while 22% revealed “the PKG provided additional information but that no alteration in patient care occurred based on this information,” according to the researchers.

The personalized monitoring system was found to provide new and precise information on daily off time — the period when medication is not working efficiently —  in 50% of the cases.

“Physicians … adjusted treatment nearly a third of the time based on the real-time clinical status captured during objective continuous monitoring outside the clinic setting,” the researchers wrote.

“These results demonstrate the real-world clinical benefits that PKG can provide to patients and clinicians in their continuing effort to optimize Parkinson’s therapy, and manage symptoms effectively,” said John Schellhorn, CEO of Global Kinetics Corporation. “The results of this study support the use of PKG as an important tool for individualizing therapy to best meet each patient’s unique needs.”

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Parkinson Voice Project to Host Lecture on Making the Most of Exercise Routines

PVP exercise lecture

The Parkinson Voice Project (PVP) is hosting a complimentary educational lecture that will focus on optimizing exercise strategies for Parkinson’s disease patients and caregivers.

The presentation “Packing Some ‘Punch’ Into Your Parkinson’s Exercise Routine” will take place at 10:30 a.m. CST Feb. 9 at PVP, in Richardson, Texas. It will be live-streamed on the PVP website and on Facebook. A video of the lecture will be posted online by Feb. 15. (Those who wish to attend in-person may register here, or call (469) 375-6500 for more information.)

The session will address the importance of exercise for those with Parkinson’s in managing symptoms and maximizing function, as well as cutting-edge concepts in exercise strategies. The hope is that participants will better understand how to apply specific training to address specific impairments. The lecture also will explore why boxing training has become a popular way for patients to fight symptom progression.

By lecture’s end, it is hoped participants will be able to describe physical motor challenges associated with Parkinson’s disease, list three physical therapy exercises specifically developed to treat Parkinson’s, and describe three benefits of non-contact boxing for those diagnosed with the disease.

The lecture will be presented by Michael Braitsch — also known as “Dr. Mike”  — a board-licensed doctor of physical therapy, a former amateur boxer, a kinesiology professor, and an internationally certified fight referee. In addition to treating individual patients, Braitsch leads group exercise programs to help people with chronic conditions move and feel better. 

A board member of the Adaptive Martial Arts Association and the University of Texas Southwestern Medical Center Adaptive Sports Expo, he’s also actively researching the effects of non-contact boxing training on Parkinson’s-associated impairments. In addition, Braitsch offers Tai chi and South Paws boxing classes for Parkinson’s patients.

According to PVP’s website, Braitsch hopes to foster community wellness by changing the way physical therapy is structured for people with chronic and progressive conditions.

Held at PVP’s Clark and Brigid Lund Parkinson’s Education Center, the presentation is part of the Parkinson’s Lecture Series featuring disease experts. On Jan. 12, PVP hosted a lecture that emphasized nutritional health and disease management. More lectures this year will include “New and Emerging Therapies in Parkinson’s,” “Dance for Parkinson’s,” and “The Power of Perseverance for Living with Parkinson’s.” Visit this site for a complete listing.

The non-profit PVP aims to preserve the voices of those with Parkinson’s and other neurological diseases through intensive speech therapy, continued support, research, education and community awareness. It hopes to team up with other speech language pathologists to reproduce its SPEAK OUT! and LOUD Crowd therapy programs globally. By marrying speech, voice and cognitive exercises, the programs seek to lessen speech problems related to Parkinson’s.

In a related Parkinson’s News Today story, experts contend that exercise that motivates Parkinson’s patients to push limits can offer a range of benefits. 

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Gene Therapy Preserves Nerve Fibers in Mouse Model of Severe Neurodegeneration

Gene therapy

An investigational gene therapy was able to preserve nerve axons — long projections that connect nerve cells and transport information — in a mouse model of severe axonal degeneration.

Because axon degeneration precedes the death of neurons in several neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis (ALS), the findings support this therapy’s potential as an effective treatment.

The study, “Gene therapy targeting SARM1 blocks pathological axon degeneration in mice,” was published in the Journal of Experimental Medicine.

Axons, or nerve fibers, are the long projections of a nerve cell, which conduct electrical impulses away from the cell body to other nerve cells, muscles, and glands. There is currently no treatment that effectively inhibits axon degeneration.

When an axon is injured, a protein called SARM1 becomes activated and triggers axons to self-destruct. In healthy nerve cells, this protein is switched off. Deleting the gene that codes for this protein, the SARM1 gene, has been shown to have a protective effect against axonal degeneration after injury in both a fruit fly model and a mouse model.

SARM1 acts as an enzyme that destroys metabolic factors needed for axons to work properly. It works by rapidly degrading a metabolite, called NAD+, causing a metabolic failure in neurons that trigger axonal degeneration. When this protein is mutated, it prevents rapid energy loss and subsequent destruction of axons.

SARM1’s multiple components must bind together for the protein to work properly. If one of these components is changed, the protein’s assemblage is faulty and unable to function. As such, scientists only have to alter or mutate a part of the protein to inhibit its function.

Researchers at St. Louis’ Washington University School of Medicine have developed a gene therapy to block the activity of SARM1.

The team introduced single mutations, affecting only one nucleotide — the building blocks of DNA — in the SARM1 gene, which resulted in the production of a faulty SARM1 protein. Similar to neurons without the SARM1 gene, when this gene therapy was inserted into nerve cells grown in the laboratory, no axonal degeneration was observed.

Accordingly, in injured neurons with a normal SARM1 protein, NAD+ levels were reduced. However, upon treatment with the gene therapy, they remained constant.

Researchers then treated neurons with vincristine, a chemotherapy agent, to simulate nerve cell damage. Two days later, the treatment resulted in axonal fragmentation. However, neurons that received the gene therapy remained intact and had normal metabolic activity — proof of how the therapy was able to inhibit SARM1 function.

To test the gene therapy in living organisms, the team used an inactive virus — adeno-associated virus (AAV) — as a vehicle to deliver the therapy into nerve cells of a mouse model of severe axonal degeneration. Researchers had induced a severe nerve injury in the sciatic nerve to trigger axonal degeneration.

Within five weeks, the viral vector containing the altered SARM1 gene was present in several of the affected nerves, including peripheral nerves and spinal cord nerve cells.

In animals treated with the gene therapy, their axons remained intact up to 10 days after nerve injury, and neurons preserved their normal conformation, architecture and myelin — a protective coating around nerve fibers — thickness.

In control (untreated) mice, there was almost a complete (99%) loss of axons at sites of nerve injury.

“With our viral gene therapy, we delivered a mutated form of SARM1 that is not only inactive itself but also blocks normal SARM1 proteins that have become activated in mice with nerve injuries,” senior author Jeffrey D. Milbrandt, MD, PhD, said in a university news release. “For a long time, viral gene therapy was a pipe dream, but there are now a number of ongoing clinical trials in other disorders that suggest we are on a promising track.”

“This has the potential to be transformative because it cuts across so many diseases,” said co-senior author Aaron DiAntonio, MD, PhD. “Rather than addressing a single disease, it is potentially a treatment for a disease process that is shared among many different neurodegenerative disorders.”

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FDA Declines to Approve APL-130277 for Treating ‘Off’ Periods; More Information Requested

APL-130277.

The U.S. Food and Drug Administration (FDA) has told Sunovion Pharmaceuticals that it is unable to approve APL-130277 (apomorphine sublingual film) in its present form for the treatment of Parkinson’s disease “off”  periods.

Sunovion submitted new drug application for APL-130277 in April 2018. Now the FDA has now issued a “complete response letter” in which it requests additional information, but no new clinical trials.

Off periods in Parkinson’s are characterized by the reappearance or worsening of symptoms — such as tremors and dyskinesia (involuntary movements) — due to a gradual decline in levodopa’s effectiveness as a therapy. About half of all patients on levodopa experience off episodes, which, although frequent in the morning after awakening, may occur multiple times throughout the day. These episodes become more frequent and severe as the disease progresses.

Noting the frequency and scarce treatment options for off periods, Antony Loebel, MD, Sunovion’s executive vice president and chief medical officer, said in a press release that “Sunovion remains committed to working with the FDA to address its requests so that we can bring apomorphine sublingual film (APL-130277) to patients as expeditiously as possible.”

Currently, Parkinson’s patients in the U.S. have only apomorphine — brand name Apokyn (apomorphine hydrochloride, US WorldMeds), as an approved medicine for off periods. Apomorphine is able to enter the brain quickly and, similar to levodopa, stimulate dopamine receptors to provide short-term relief. However, Apokyn’s subcutaneous (under-the-skin) delivery may cause pain and injection-site reactions.

In turn, APL-130277 is a sublingual (under the tongue) formulation of apomorphine, intended to provide on-demand and fast-acting lessening of all types of off episodes, meaning those that are unpredictable, and those that occur at the end-of-dose or after awakening in the morning. It was designed  to be taken up to five times a day, no sooner than two hours from the prior dose.

APL-130277 contains a two-layer film, one with apomorphine and the other including an acid neutralizer to improve absorption and reduce oral irritation. Compared to Apokyn, APL-130277 is less likely to induce nausea due to a more gradual absorption, said Loebel, who is also the head of global clinical development for Japan-based Sumitomo Dainippon Pharma Group (which owns Sunovion) in an October 2018 interview with Parkinson’s News Today.

The FDA new drug application for APL-130277 was supported by a 12-week, double-blind Phase 3 trial (NCT02469090). The results showed that, within 30 minutes of dosing, the treatment enabled a clinically meaningful reduction in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part 3 score, a measure of Parkinson’s motor symptoms, in comparison to placebo.

The benefits were seen as early as 15 minutes post-dose and were maintained for 90 minutes, when the last analysis was conducted. Similar improvements were seen at weeks four, eight and 12. A higher percentage of patients achieving a full-on response — or control of motor symptoms — within 30 minutes with APL-130277 also was observed.

The therapy was well-tolerated, with most treatment-related side effects being mild to moderate and reversible.

Most patients took the treatment two or three times each day, though no minimum dose was required. “So that indicates they’re getting a benefit and … it’s not given on a prescribed schedule — they chose to use it two or three times a day,” David Blum MD, Sunovion’s global head of neurology clinical research, said.

The company is still recruiting for a 24-week, open-label extension study (NCT02542696) at multiple locations. A total of 226 participants are expected to use APL-130277 at 10-35 mg. Outcomes focus on the safety and tolerability of longer-term use, including patient response without Tigan (trimethobenzamide), an antiemetic (a medicine against vomiting and nausea) required as pretreatment to Apokyn.

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Parkinson’s Disease Is a Silent Thief

marriage

Sherri Journeying Through

I read somewhere that Parkinson’s disease robs people of who they were, who they have been, and the person others have known. It affects marriages, too. I read this on the tailcoat of writing about Parkinson’s and the role it can play in the intimacy of marriage.

It’s downright hard living with this little monster. One tries to maintain a sense of normalcy, but that is often difficult when medications decide to “turn off” and stop functioning; when tremors won’t cooperate so a person can write their own name; or when fingers won’t move to tie shoes, button a shirt, hook a bra, or buckle a belt. Put all the physical frustrations together with the cognitive ones, and it can produce one frustrated spouse — either the patient or the caregiver, or both.

Parkinson’s is a thief, indeed. It may rob the person who actually has Parkinson’s, but we also need to remember that it robs the caregiver, too.

I have read or been told many times about a partner of someone with PD who decided to leave the relationship and call it quits. Is that fair? No way. Especially if they had repeated those infamous words, “Till death do us part.” But realistically, it’s not fair for either party. It’s not fair for the one with PD or their partner, who finds themselves having to care for a spouse in ways they hadn’t anticipated in the “happily ever after.”

Life can seem unfair. People change with or without a disease. They bottle things up and refuse to talk about whatever is ailing them, eventually making things appear far worse than they really may be. They think the only way to be free from the perceived culprit that vies for their happiness is to turn around so they don’t have to face it anymore. The problem? They often don’t head into anything better. 

A key component of a good marriage is communication. When dealing with a chronic illness, it is even more important. It’s critical for both partners to talk about how they feel and how the disease affects them.

Following are some suggestions on how to do that:

  •  Take time out regularly to talk to each other. Find a neutral spot to do it. 
  •  Turn off the television for one hour a day and read to each other, play a game, or do a puzzle, if possible.
  •  Bring back dating in your relationship. If you are unable to go to a coffee shop or some other place easily, set a regular time each week to gather at the kitchen table for coffee and cookies.
  •  Sit out on the front porch and watch people.
  •  Hold hands.
  •  Try to have a greater understanding of each other. Get some counseling to get through the tough times.

Don’t give up. There will be better days, better moments. Those are the times we live for, the times that make us want to hold on.

When I was married 39 years ago, my pastor told me that when he married couples, God tied a knot in the relationship, and the harder we pulled against one another, the stronger and tighter the knot would become. Parkinson’s is one thing in our marital relationships that can tighten that knot — if we hold on and let it.

***

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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Role of Environmental Factors in Parkinson’s Development Investigated in Review Study

environmental causes

The hallmark presence of Lewy bodies in the pathway related to sense of smell and in the gut years before a Parkinson’s diagnosis, as well as the potential cumulative impact of different triggers, may help researchers understand the environmental factors that contribute to the development of the disease, according to a review study.

The study, “The Search for Environmental Causes of Parkinson’s Disease: Moving Forward,” appeared in the Journal of Parkinson’s Disease.

Environmental factors contribute at least partially to late-onset sporadic Parkinson’s disease. Because neurodegenerative changes are too advanced to be stopped or reversed by the time a diagnosis is reached, understanding modifiable risk factors that can help to identify the disease and allow for an early intervention may lead to more successful treatment of Parkinson’s, the neurological disease with the fastest-growing prevalence.

“The greatest risk factors for [Parkinson’s] are likely environmental and not genetic,” Honglei Chen, MD, PhD, from Michigan State University, and Beate Ritz, MD, PhD, from the University of California Los Angeles, said in a press release. “Yet we know relatively little about environmental causes or triggers. Identifying these and defining ways to reduce their impact will be great research challenges for the coming two decades.”

Environmental factors may trigger Parkinson’s or modify its progression during the prodromal (early) stage, in which early symptoms or signs are present, but clinical diagnosis is not yet possible. Among the reported factors, smoking, coffee, exercise, plasma urate, and use of ibuprofen have been linked to a lower risk of Parkinson’s, while pesticide exposure and traumatic brain injury have been associated with a greater risk.

Apart from two pesticides known as rotenone and paraquat, researchers have had difficulties in providing evidence that other risk factors can cause the disease. Reverse causation — meaning that Parkinson’s changes lifestyle and behavior before a clinical diagnosis rather than the other way around — has been proposed as an explanation for the link between these environmental triggers and Parkinson’s in its early stages.

“This prodromal stage is of major interest for prevention efforts,” the researchers said in the release, adding that the discovery of Lewy bodies — protein aggregates mainly composed of alpha-synuclein that are characteristic of Parkinson’s — in the olfactory pathway and the digestive tract made targeting factors that enter the body via the nose or gut “even more important.”

The Braak hypothesis presents a potential explanation for environmental contributions in Parkinson’s prodromal development. It suggests that Lewy pathology starts in the brain’s olfactory bulb — an area of the brain involved in the sense of smell — or in enteric (gut) nerves (nerve cells that control the function of the gastrointestinal tract) years, if not decades, before reaching the substantia nigra — an area of the brain key in the control of movement that shows progressive loss of dopamine-producing neurons in Parkinson’s disease.

Findings such as a reduced sense of smell and constipation years before a Parkinson’s diagnosis have supported the Braak hypothesis. Pesticides and other environmental toxins such as air pollutants, of which there is growing evidence of harmful effects on cognitive function, organic solvents, and meats cooked at high temperatures may lead to Parkinson’s through these pathways, although a proinflammatory gut microbiome — the community of bacteria, viruses and fungi that lives in the gut — has also been proposed as a potential starting point. Certain genetic factors may also interact with these environmental causes to boost the risk for the disease.

Besides the Braak hypothesis, the scientists also discussed reported epigenetic differences — alterations in gene function but not in the DNA sequence itself — in the blood and saliva of people with Parkinson’s as well as the importance of lifelong exposure to environmental triggers.

The exposome, which refers to all environmental exposures over a lifetime, suggests that multiple environmental stimuli combine to increase the risk of Parkinson’s. This has been shown with traumatic brain injury and paraquat exposure, and with smoking combined with factors such as caffeine intake and physical activity.

“We are at an exciting moment to unveil environmental contributions to [Parkinson’s] development and progression by taking a life-course approach, and utilizing novel tools to assess environmental exposures,” the researchers said.

While they caution that the long duration of the prodromal stage complicates understanding the extent to which environmental factors contribute to Parkinson’s, the investigators “nevertheless believe it will be possible to assess long-term exposures through large-scale environmental monitoring and by using novel biomarkers that reflect the exposome.”

Both the Braak hypothesis and the exposome concept provide “a theoretical framework for scientists to design future studies to decipher the environmental causes of [Parkinson’s] and develop early interventions to halt the progression to the characteristic motor dysfunction in [Parkinson’s],” they concluded.

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Neurocrine, Voyager Team Up to Develop VY-AADC for Parkinson’s Disease

Neurocrine Biosciences

Neurocrine Biosciences and Voyager Therapeutics have joined efforts in a new strategic collaboration to further develop and market Voyager’s gene therapies VY-AADC for Parkinson’s disease and VY-FXN01 for Friedreich’s ataxia.

With this partnership, Neurocrine Biosciences will apply its expertise in neuroscience, drug development, and commercialization to help expedite the development of Voyager’s gene therapy programs.

“We are excited to collaborate with Voyager to advance our shared mission to discover and develop medicines that can benefit the lives of people with serious neurological disorders,” Kevin Gorman, PhD, CEO of Neurocrine, said in a press release.

Neurocrine will have the opportunity to expand its “clinical development pipeline addressing neurological disorders, leverage Voyager’s expertise in [central nervous system]-focused gene therapy, and develop potential treatments for diseases,” he said.

Based on the terms of the agreement, Neurocrine is going to finance the Phase 2-3 pivotal program for VY-AADC for Parkinson’s disease. After the completion of the Phase 2 RESTORE-1 trial (NCT03562494), in which the therapy is currently being evaluated, Voyager will have the option to decide whether it will share commercialization responsibilities or give Neurocrine full rights to the therapy in the U.S. in return for milestone payments and royalties.

A similar plan was established for the future of VY-FXN01 for Friedreich’s ataxia. In addition, Neurocrine also agreed to fund two additional gene therapies programs yet to be determined.

“This is a transformational collaboration for Voyager that greatly enhances our efforts towards becoming the leading, fully-integrated gene therapy company focused on severe neurological diseases while allowing us to continue to invest in our additional pipeline programs and platform,” said Andre Turenne, president and CEO of Voyager.

VY-AADC is an investigational gene therapy that uses a modified and harmless adeno-associated virus to deliver the ADDC gene directly into the putamen brain region, which is involved in movement control.

This gene provides instructions for making an enzyme, called 1-amino acid decarboxylase (AADC), that converts levodopa (the gold standard treatment for Parkinson’s) to dopamine — a signaling molecule that acts as a messenger between brain cells and is present at lower levels in Parkinson’s patients.

Researchers believe that with a single administration of VY-AADC, it may be possible to achieve the sustainable conversion of levodopa to dopamine, enhancing its clinical effects and significantly restoring the motor function of Parkinson’s patients.

The ongoing RESTORE-1 trial is currently recruiting individuals who have been diagnosed with Parkinson’s for four years or more and who are not responding well to oral medications. Eligible patients also need to have at least three hours of daily “off” periods — characterized by the return of motor and non-motor symptoms when levodopa’s effects wear off.

The study will evaluate the impact of VY-AADC on patients’ motor symptom fluctuations, measured by a self-reported patient diary and response to levopoda treatment. Researchers will also evaluate changes in quality of life and global function, as well as changes in non-motor symptoms, upon treatment with VY-AADC compared to placebo.

VY-AADC received the regenerative medicine advanced therapy designation from the U.S. Food and Drug Administration in June 2018 for the treatment of therapy-resistant motor fluctuations in Parkinson’s patients.

The FDA’s decision was supported by positive results of a Phase 1b trial (NCT01973543) in 15 Parkinson’s patients, in which a single administration of the therapy induced robust and durable improvements in patients’ motor function up to three years after treatment.

VY-AADC treatment also effectively increased AADC enzyme activity, allowing patients to reduce their doses of oral levodopa and improving their quality of life.

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