Stars Come Out For ‘Light Of Day Winterfest’ Benefiting The Fight Against Parkinson’s Disease

January 17, 2019

https://youtu.be/WTunsY9nPXo

Musicians are gathering together this week in NYC and on the Jersey Shore for charity performances to benefit Parkinson’s disease research. (Photo: CBS2)

ASBURY PARK, N.J. (CBSNewYork) — What started off as a private party on the Jersey Shore has become a festival that has raised millions of dollars for Parkinson’s disease.

Many will tell you it’s rock music’s most celebrated charity events. CBS2’s Valerie Castro spoke to the man behind the Light of Day Winterfest on Thursday.

All eyes are glued to the performers on stage, but every year it’s a man and his noble cause the audience truly appreciates.

“I am amazed every day,” Bob Benjamin said.

In 1996, Benjamin was diagnosed with Parkinson’s. Instead of giving up, the band manager decided to do the opposite. He turned his birthday party that year into a charity event for the disease.

“It’s the only way I knew how to fight,” he said.

He had no idea that all these years later his efforts would lead to almost $5.5 million raised for Parkinson’s and a new foundation, Light of Day.

“It’s a disease that isolates. It debilitates. We are always hoping for that breakthrough that is really going to make a significant change in their lives,” said Tony Pallagrosi, the executive director of the foundation.

Every year, rock ‘n’ roll bands have gathered to perform during the 10-day festival. Glen Burtnik from the group The Weeklings brought down the house during a Manhattan kickoff event on Wednesday night.

“You have an audience that comes to see you making music and this is an opportunity to help out people,” Burtnik said.

Bruce Springsteen has performed in the past and the star-studded event has attracted other celebrities like actor Vincent Pastore from “The Sopranos.” But spectators and those diagnosed will tell you it’s Parkinson’s disease, and the fight to end it, that they want to concentrate on.

“It’s more than the music. It’s the cause. So we have to remind people why they’re here and where the money is going and all the good work that they do,” said Alan Jackowitz, who was diagnosed in 2008.

“It’s amazing all the support we get year after year,” Benjamin added.

Amazing support and incredible sounds, all in one place, to beat Parkinson’s.

The concert festival will conclude this weekend in Asbury Park with many acts. For more information on ticket pricing and event details,  January 17-21, 2019.

http://lightofday.org/events

https://health.einnews.com/article_detail/473955481/D2QfaMp6atZ00rYL?n=2&code=lAb0qDE0aV13cmUw&utm_source=NewsletterNews&utm_medium=email&utm_campaign=Parkinson%27s+Disease+News&utm_content=article

Science Says Eating Chocolate Every Day Is Good For Your Brain

JAN 17, 2019 by CAROLINE PICARD 

Forget about an apple a day. If you really want to keep the doctor away, try a piece of chocolate instead. Regularly snacking on cocoa-flavored treats can help protect your brain from cognitive decline, according to a new review from the University of L'Aquila in Italy.

Packed with both antioxidants and iron, dark chocolate has already made a name for itself as a smart choice for dessert lovers. Its potential brain-boosting powers only sweeten the deal. Eating some every day helps improve attention, processing speed, working memory and verbal fluency, based on the recent compilation of past studies. 

"Regular intake of cocoa and chocolate could indeed provide beneficial effects on cognitive functioning over time," said review authors Valentina Socci and Michele Ferrara. Their analysis published in Frontiers in Nutrition found that seniors at risk for memory decline received the biggest perks from eating chocolate. Regularly choosing the treat could help improve vital thinking processes over time.

A quick snack may provide some short-term advantages too. Eating cocoa also helped young and healthy adults perform better on tough cognitive tests almost immediately, although the effect was more subtle.

The powerful benefits come from cocoa flavanols, a compound known for its health benefits. Dark chocolate packs in way more flavanols than its milk counterpart, but you can also find them in apples, pears and grapes, among other foods. 

The special type of flavonoid supports a healthy cardiovascular system and could increase blood flow to a part of the brain particularly affected by aging, Socci and Ferrara say. Both of them indulge in a little dark chocolate every day, but warn against eating too much, especially if the bar's packed with sugar and other additives.

Luckily, choosing chocolate can also stave off cravings for more indulgent desserts later on, says Jaclyn London, M.S., R.D., C.D.N., Nutrition Director at the Good Housekeeping Institute. "Having an ounce of chocolate per day, or about 150 to 200 calories, has a number of different benefits," she says. "While no food is a miracle-worker, I'm a huge proponent of treating yourself with chocolate daily."

While you probably shouldn't give up on apples entirely, adding a little dark chocolate into the mix doesn't hurt. Hey, you don't have to tell us twice! 

[h/t Science Daily

https://www.delish.com/food-news/a25939326/chocolate-brain-benefits/?utm_medium=social-media&utm_campaign=socialflowFBDEL&utm_source=facebook&fbclid=IwAR1etX85Z4j10YoLPQyfL6qeYwQ_48AGU6RKdCk0kvbP7LBjaLRVUsya9Tc

‘Bananas and Beans, not Burgers’: High-Protein Meals and Levodopa

JANUARY 18, 2019 Dr. C

No one told me that breakfast bacon, ham, or sausage would make me feel awful!

I had seen my off-periods worsen after a heavy meat meal, but I shrugged it off as “just a bad off-period.” Now, after being on levodopa for five years, I am positive that animal protein meals are a serious issue. Overlapping a high meat meal with levodopa can result in not just an off-period, but also one that lasts much of the day.

“Bananas and beans, not burgers” is the mantra to remind me that diet is very important in the development of a rehab plan for folks with PD. I am not a nutritionist. I am writing from the perspective of a PD patient warrior and rehab clinician.

Research suggests that changes to your diet could help alleviate some symptoms of your PD. The American Parkinson Disease Association (APDA) notes that levodopa crosses the wall of the small intestine via molecules in the intestinal wall that transport amino acids. When dietary protein (beef, chicken, pork, fish, eggs, nuts, and dairy) is also present in the small intestine, fewer transporters are available for levodopa to use. We may experience the “protein effect” when the medication competes with a high-protein meal.

One of the most compelling statements in a 2014 study published in Frontiers in Aging Neuroscience is that a “growing body of evidence suggests that nutrition may play an important role in PD.”

The study “Irregular gastrointestinal drug absorption in Parkinson’s disease” in the journal Expert Opinion on Drug Metabolism & Toxicology states that levodopa transit time in the small intestine is approximately three hours. Therefore, gastric emptying is a major determining factor for the onset of symptom relief. When PD delays gastric emptying, it has the potential to cause motor fluctuations, known to us as off-periods.

Research also shows that with your microbiome (the microorganisms in your body), a relationship exists between Parkinson’s disease and improved gut health. In “Parkinson’s disease and bacteriophages as its overlooked contributors,” published in the journal Scientific Reports, George Tetz and his colleagues examined the viruses that live in the gut, as well as the role the microbiome may play in Parkinson’s disease. According to Parkinson.org, “this has sparked the idea that we might be able to improve the symptoms if we change the microbiome through diet or other ways. … These bacteria play a role in the processes that produce dopamine and affect the intestine’s ability to absorb.”

Like many aspects of Parkinson’s symptoms, the protein effect is highly variable. Some people do not experience it at all. Others are extremely sensitive to protein’s effect on medication absorption. This diet concern was presented at my local PD support group, and the group’s PD warriors and caregivers agreed almost unanimously with having experienced or witnessed the adverse effects.

It typically becomes more of an issue as PD progresses. The APDA suggests that if someone experiences the protein effect, two potential strategies might help. One is to refrain from eating protein during the day, eating it at night instead, when the medication’s effect is less critical. The second is to distribute protein intake evenly throughout the day so that medication absorption is enhanced during that time.

The solution I have found that works best for me has two parts. First, I space the levodopa dosing so that it occurs between meals to minimize absorption issues. Second, I eat the day’s moderate meat meal at lunch, not dinner or breakfast.

Reducing meat in your diet may be beneficial not just to levapoda absorption. An amazing study on diet and overall health by Thomas Campbell and T. Colin Campbell, called “The China Study,” clearly showed that decreasing meat intake is a good change for all of us. Bananas and beans, not burgers.

What diet changes have you found to be helpful? 

***

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.

https://parkinsonsnewstoday.com/2019/01/18/bananas-beans-not-burgers-high-protein-meals-levodopa/

Mutations in Gene Associated With Hereditary Parkinson’s Disease Lead to Toxic Accumulation of Manganese

JANUARY 18, 2019 BY PATRICIA INACIO, PHD 

Researchers have found that mutations in a gene linked to hereditary forms of Parkinson’s disease — SLC30A10 — cause accumulation of toxic levels of manganese inside cells, which disturbs protein transport and alters nerve cell function, leading to parkinsonian symptoms.

The study “SLC30A10 Mutation Involved in Parkinsonism Results in Manganese Accumulation within Nanovesicles of the Golgi Apparatus” was published in the journal ACS Chemical Neuroscience.

Manganese is an essential metal that helps enzymes carry out their functions in the body. However, too much manganese is toxic, especially for the central nervous system (brain and spinal cord), where its accumulation can lead to parkinsonian-like syndromes.

The SLC30A10 gene encodes an important manganese transport protein, which sits at the membrane of cells and pumps out manganese, to protect cells against this metal’s toxicity. However, mutations in the SLC30A10 gene block the protein’s pumping activity, resulting in manganese accumulation.

Mutations in this gene have been identified as the cause of new forms of hereditary Parkinson’s disease.

“Understanding the means by which mutations in SLC30A10 alter cellular Mn [manganese] homeostasis [manganese equilibrium] is expected to enhance understanding of the principles underlying Mn toxicity itself,” researchers wrote, which may render important information to fight certain forms of familial Parkinson’s disease.

A team of French researchers used advanced imaging techniques to find where manganese accumulates inside cells (cell lines available for laboratory research) carrying disease-causing SLC30A10 mutations versus cells carrying a normal, functional SLC30A10 gene (control cells).

Intracellular manganese levels were undetectable in control cells, confirming cells’ ability to expel the metal and avoid its toxicity. On the contrary, manganese levels were higher in cells carrying disease-causing SLC30A10 mutations.

The team then looked at cells that lacked SLC30A10 and were exposed to increasing levels of manganese. Researchers found that manganese accumulated in an organelle, called the Golgi apparatus, that works as the cell’s dispatching center for proteins. The same was true for cells carrying disease-causing SLC30A10 mutations.

Mutant SLC30A10 proteins lost their ability to expel manganese out of the cells, with cells behaving as if they had no SLC30A10 protein at all.

Using the an imaging technique known as Synchrotron X-ray fluorescence spectrometry, which allows researchers to look deeper into cells and their smaller structures, the team discovered that the main compartment for manganese accumulation in SLC30A10 mutated cells were tiny vesicles released from the Golgi apparatus.

These vesicles are important mediators of communication inside the cell. Researchers believe that disturbing this vesicular trafficking is probably the root of the toxicity induced by the disease-causing mutations of SLC30A10.

“It would be interesting to investigate whether Mn causes defects in Golgi vesicular trafficking and consequently on neurotransmitters,” researchers wrote.

Moreover, these results suggest that small molecules targeting the mutated SLC30A10 protein at the cell surface could become a potential therapeutic strategy.

Future experiments will show if a similar pattern of manganese accumulation is seen in animal models of Parkinson’s disease.

https://parkinsonsnewstoday.com/2019/01/18/mutations-slc30a10-gene-toxic-levels-manganese-hereditary-parkinsons/

Subjective Cognitive Decline Could Help Predict Parkinson’s Dementia, Study Contends

JANUARY 18, 2019 BY CATARINA SILVA IN NEWS.

Subjective cognitive decline in Parkinson’s disease could predict the development of dementia. As such, a suitable cognitive screening test could help provide an accurate diagnosis and prognosis.

The study with those findings, “Subjective cognitive decline and progression to dementia in Parkinson’s disease: a long-term follow-up study,” was published in Journal of Neurology.

Even during the early stages of disease, mild cognitive impairment can affect non-demented Parkinson’s patients, and is considered a risk factor for the development of dementia (PDD).

In fact, the prevalence of PDD increases as the disease progresses: from 28% after five years of evolution to 80% after 20 years of the disease.

Subjective cognitive decline — self-reported acquired difficulties with cognitive functioning — is common in the elderly and can be used as a predictor of dementia. In Alzheimer’s disease, subjective cognitive decline has been linked to disease-related tissue/molecular changes and a higher risk for dementia development. However, the predictive value of this type of cognitive status impairment has not been demonstrated yet in Parkinson’s disease.

Scientists from the University of La Laguna, Spain, investigated the neuropsychological profile of subjective cognitive decline in Parkinson’s disease and explored which components could better predict the development of PDD. The team also compared different screening tests to assess subjective cognitive complaints.

A total of 43 Parkinson’s patients and 20 healthy subjects were subjected to neuropsychological examination using a battery of cognitive tests. All patients were being medicated for Parkinson’s and were evaluated during their “on” state — when they are responding to medication and have reduced symptoms.

Subjective cognitive decline was diagnosed using two distinct approaches. A semi-structured interview in which the patient provided his/her subjective opinion on his/her attention, memory, spoken language, naming, written language, visuospatial skills and executive functions; diagnosis was considered when the patient had at least one cognitive complaint. Additionally, a subjective cognitive decline diagnosis also was established on the basis of the interview question concerning memory complaint.

For a mild cognitive impairment diagnosis, investigators followed the criteria proposed by the Movement Disorder Society (MDS)

Based on the results of the interview and on the MDS Task Force criteria, patients were diagnosed as having either subjective cognitive decline or mild cognitive impairment. Of the 43 patients, 13 (30.2%) were diagnosed with subjective cognitive decline, 22 (51.2%) with mild cognitive impairment and 8 (18.6%) had no subjective cognitive complaints. Difficulties in naming and memory were the most frequent cognitive complaints.

Based on memory complaints alone 10 patients (23.25%) were diagnosed with subjective cognitive decline. Interestingly, 10 of the 22 (45.45%) who had been diagnosed with mild cognitive impairment reported no memory complaints.

Mild cognitive impairment subjects performed poorer in the processing speed (the time it takes a person to do a mental task), executive functions (a set of mental skills that helps with organization and regulation), visuospatial skills, memory, and language domains, compared to the other groups.

There were no significant differences between healthy participants (controls)  and Parkinson’s disease patients with subjective cognitive decline in any of the neuropsychological measures.

The team also assessed how many patients diagnosed with subjective cognitive decline progressed to dementia after a mean follow-up of 7.5 years. Fifty percent of mild cognitive impairment patients, 33.3% of individuals diagnosed with subjective cognitive decline, and 14.3% of patients without subjective cognitive complaints developed dementia, which was found to be associated with a poor performance in verbal and visuospatial memory and naming at the beginning of the study.

Additionally, both the language and memory domains were good predictors of dementia development.

“These results are highly relevant for future investigations and also for clinicians: the [subjective cognitive decline] assessment is frequently the first step of cognitive examination and can influence future decisions (e.g., to administer a screening test or a comprehensive neuropsychological assessment),” researchers wrote.

“Assessments that do not include procedures to adequately explore cognitive complaints may underestimate the proportion of [Parkinson’s-related subjective cognitive decline] and, therefore, [mild cognitive impairment] and thus misclassify patients as [Parkinson’s disease] with normal cognition, especially when brief cognitive examinations are chosen,” they concluded.

https://parkinsonsnewstoday.com/2019/01/18/study-subjective-cognitive-decline-parkinsons-dementia/

Struggles in Managing Iatrogenic Polypharmacy: Case Study

Brandon May      

January 18, 2019

Even the use of as few as 2 concomitant drugs can introduce the risk for drug interactions and subsequent adverse effects.

A case study of an elderly patient receiving polypharmacy and presenting with new neurological-related symptoms raises the concern that iatrogenic polypharmacy may obscure the presence of a disease and delay appropriate diagnoses and treatment. The case study was published in the AMA Journal of Ethics.

In the presented case, an 83-year-old woman who was taking 17 different medications presented to her physician with a newly developed intention tremor, slurring of words, ataxia, and depression. The patient reported fear that she was developing Parkinson's disease, a heavy disease burden considering her other diagnosed health issues (ie, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, diabetes complicated by gastroparesis, and hypertension). The patient also reported feeling unsure as to whether she had a neurodegenerative disorder or whether her medications were causing her symptoms. Her symptoms worsened after recent hospitalizations, all of which corresponded with the prescription of several new medications.

This case suggests that iatrogenesis, or physician-generated illness or injury, caused the woman's neurological symptoms. Further, iatrogenic polypharmacy, if a contributing factor to this case, is suggested to be a disease itself, and 1 in which treatment with further medications may be unsound. Considering as few as 2 concomitant drugs can introduce the risk for drug interactions and subsequent adverse effects, iatrogenic polypharmacy requires additional investigation to determine which steps clinicians should take in identifying, diagnosing, and managing medical-induced iatrogenesis.

In some instances, iatrogenesis resulting from polypharmacy can be managed by clinician-patient discussion regarding which medications are necessary and which medications can be safely discontinued. If possible, this may reduce and potentially eliminate the patient's new symptoms, causing the physician to make a clearer decision as to whether a new disease has truly developed or whether the patient was merely experiencing drug interactions

"More research needs to be done that is responsive to actual prescribing practices so that, in turn, clinicians can make more informed decisions when weighing potential benefits and risks of adding medications to a patient's existing drug regimen," author Christine Wieseler, PhD, from the Department of Philosophy at the University of Louisville in Kentucky, wrote. "While it seems inevitable that clinicians will need to prescribe multiple medications to some patients in order to manage their conditions, better health outcomes are likely when polyprescribing involves careful coordination among clinicians, avoids unnecessary medications, and is informed by an evidence base that takes into consideration the reality that many patients take multiple medications."

Reference

Wieseler C. When should iatrogenic polypharmacy be considered a disease? AMA J Ethics. 2018;20(12):E1133-E1138.

https://www.medicalbag.com/ethics/iatrogenic-polypharmacy-management/article/828258/

Parkinson's Subtypes Predict Prognosis

 Sue Hughes     January 18, 2019

Patients with Parkinson's disease may be stratified on the basis of specific subtypes that progress differently and that are associated with different prognoses, a new study suggests.

"We have found that it is possible to accurately predict prognosis, disability, and survival of patients with Parkinson's disease by classifying them into different clinical subtypes at the time of diagnosis," senior author Thomas Warner, MD, University College London Queen Square Institute of Neurology, United Kingdom, told Medscape Medical News.

"These subtypes may have different underlying problems affecting the nervous system which now need to be identified and which may lead to the development of treatments for specific clinical subtypes," he added.

The study was published online in JAMA Neurology on January 14.

The researchers used life course clinical information from 111 Parkinson's patients who had donated their brains to research after death.

They developed a classification system that is based on the severity of the cardinal movement problems in Parkinson's and key nonmotor symptoms, including cognitive function, autonomic symptoms (control of blood pressure, urinary function), and REM (rapid eye movement) sleep behavior disorder according to the clinical impression of the treating physicians.

"Together with the classical motor features, a simple assessment of relevant nonmotor symptoms can now allow clinicians to provide an accurate estimation of the disease course at the time of diagnosis, allowing better counseling, management of symptoms, and planning care of potential complications," Warner said.

Three main subtypes have been proposed:

1. Mild-motor predominant: Motor and all nonmotor scores less than the 75th percentile
2. Diffuse malignant: Either motor score greater than the 75th percentile and at least one nonmotor score greater than the 75th percentile or all three nonmotor scores greater than the 75th percentile
3. Intermediate: All those individuals not meeting criteria for other subtype.
   Warner explained that in the mild-motor predominant category, patients present with mainly movement problems. It is associated with the best prognosis and survival. In the diffuse malignant subtype, patients have a combination of motor and nonmotor symptoms on presentation. This subtype represents a more aggressive and progressive clinical picture. The intermediate group has an intermediate prognosis.
   He noted that the neurology community has always recognized that patients who present with prominent tremor often have a better prognosis. "These would now be considered as the mild motor predominant group," he said.
   In the current study, 48.7% of patients were categorized as having the mild-motor predominant subtype, 35.1% as having the intermediate subtype, and 16.2% as having the diffuse malignant subtype.
   Patients with the mild-motor predominant subtype were significantly younger at diagnosis, responded better to levodopa, and received a higher levodopa equivalent dose. Patients with the diffuse-malignant subtype were older, were almost all men, responded more poorly to levodopa, and were more frequently misdiagnosed as having an atypical parkinsonian syndrome in life.
   Patients with the diffuse malignant subtype reached all prognostic milestones earlier in the disease course (hazard ratio, 10.90; P < .001) and had the shortest survival from diagnosis (8.1 years vs 15.8 years for the mild-motor predominant group).
   Staging of Lewy pathology and Alzheimer disease–related pathology did not differ between subtypes, although these factors were associated with different rates of progression, and the latter was associated with age at death.
   Warner explained that in the mild-motor predominant category, patients present with mainly movement problems. It is associated with the best prognosis and survival. In the diffuse malignant subtype, patients have a combination of motor and nonmotor symptoms on presentation. This subtype represents a more aggressive and progressive clinical picture. The intermediate group has an intermediate prognosis.
   "Our findings confirm that these subtypes are a reasonable way of classifying patients, add much needed prognostic information, as we have data on the whole disease course and pathology, and we have simplified the information needed at diagnosis to make the classification easier to implement in the clinic," Warner said.
   Their study took into consideration the whole life course of Parkinson's in cases definitively diagnosed by neuropathologic study of the brain, he added. "In life, there is a level of diagnostic error of clinical diagnoses, as other conditions can mimic Parkinson's. It is important to have data over the whole duration of the disease, including pathology information, to accurately define the subtypes and their prognosis."
   He also pointed out the importance of nonmotor symptoms in the diagnosis. "We have shown that the nonmotor features are not just contributors to the clinical burden, but they are also negative prognostic markers, and their evaluation should be part of every routine clinical assessment."
   Warner concluded, "Our results support the idea that different mechanisms and/or modifying factors may drive the clinical heterogeneity in Parkinson's subgroups, including the variable response to available medications seen in our study. It seems that differences in the progression of Lewy pathology and other neuropathologic changes (Alzheimer's disease pathology) are one of the factors contributing to the variability of Parkinson's disease."
   Better understanding of these and other factors will "open up the avenue for more effective individualized treatments based on the underlying pathophysiological mechanisms," he said. "Until target treatments become available, Parkinson's clinical subtyping, including nonmotor features, should be incorporated in clinical research, and the assessment of any future drugs in clinical trials should be stratified by Parkinson's subtypes which may help with the understanding of Parkinson's pathophysiology."
   The research was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center. Dr Warner receives research support from the Reta Lila Weston Medical Trust, the Brain Research Trust, Cure Huntington's Disease Initiative, the Medical Research Council, and Corticobasal Degeneration Solutions. The other authors' relevant financial relationships are listed in the original article.
   JAMA Neurology. Published online January 14, 2019. Abstract
   
   
   https://www.medscape.com/viewarticle/907995?src=rss

A New Way to Help Manage Parkinson's

• By David Blum on January 18, 2019

A broader range of treatments for this disorder offers patients a more personalized approach

The brain of a Parkinson's patient. Credit: Getty Images

Many of us have personally experienced or witnessed the impact of Parkinson’s disease (PD), a movement disorder that affects nearly 10 million people worldwide. This chronic, progressive neurodegenerative disorder leads to disability from motor impairments, such as tremors, rigidity, absence or slowness of movement and impaired balance, as well as from non-motor symptoms including sleep disruption, gastrointestinal issues, sexual dysfunction or loss of sense of smell or taste, to name a few.

The ideal outcome of PD clinical research would be to find a cure. But researchers are also looking at novel ways to administer proven Parkinson’s medicines in order to help people living with the disease better control their symptoms and maintain their regular, daily activities.

THE COMPLEXITY OF TREATMENT THAT EXTENDS OVER DECADES

The brain cells that die from PD are responsible for producing dopamine, a neurotransmitter involved in complex behaviors including motor coordination, addiction and motivation. As a result, treatment typically includes the use of levodopa—a medication that is converted into dopamine in the brain and relieves PD symptoms. For the first few years after diagnosis, many individuals’ symptoms are well controlled by levodopa.

The average age of onset is 60, but some people are diagnosed at 40 or even younger, potentially requiring treatment for decades. Over time, a patient’s response to levodopa changes, and the therapeutic window, or period when levodopa is effective, narrows, often leading to the prescription of additional levodopa or more frequent dosing of levodopa to manage symptoms.

As Parkinson’s disease progresses, a patient’s sensitivity to peak concentrations of levodopa increases. Physicians may prescribe more frequent doses of levodopa or a different formulation. They may also try COMT inhibitors or MAO-B inhibitors to extend the duration of activity for levodopa or add dopamine agonists to provide a constant level of dopaminergic stimulation.

Fluctuation of levodopa levels, either too low or too high, can cause side effects and the reemergence or worsening of symptoms. If levels of levodopa are too high, dyskinesia can result (abnormal, uncontrolled or involuntary movement). If the concentration of levodopa is too low, deterioration of motor functions can occur.

The periods that occur when levodopa concentration drops, and a patient’s motor function subsequently declines, are known as OFF episodes. Patients may experience different types of OFF episodes, such as early morning OFF, unpredictable OFF and end-of-dose wearing OFF.

The reappearance or worsening of PD symptoms during such OFF episodes can severely impact a PD patient’s ability to maintain independence and quality of life. OFF episodes may be characterized, in part, by tremor, stiffness or slow movements, and some patients describe them as a feeling of being “frozen.” OFF episodes can impact a person’s ability to speak, to get up from a bed or chair or to walk stably without assistance. Moreover, these episodes become more prevalent over time—about 40 to 50 percent of PD patients experience OFF episodes within two years of starting levodopa therapy. After nine years this rate grows to approximately 70 percent.

CHANGING THE PARADIGM OF TREATING OFF EPISODES

Treating OFF episodes remains a challenge. While some treatments are available, there are still opportunities to improve the options available for patients with Parkinson’s disease. Currently, there are immediate- and extended-release levodopa tablets, and an inhaled form of levodopa, as well as a surgically implanted tube connected to a pump that delivers levodopa directly to the intestine for up to 16 hours. Extended-release amantadine, taken daily, has been shown to reduce the total daily OFF time but does not convert an OFF episode into ON time.

In addition to the medication itself, it is also crucial to consider the way in which a Parkinson’s disease patient takes the medication. Not only can OFF episodes impact a patient’s ability to administer a therapy requiring complex instructions, but the disease also impacts the gastrointestinal system and can impair consistent absorption of medication taken orally.

Apomorphine is currently FDA-approved in an injectable form as a rescue therapy for OFF episodes. It is a fast-acting dopamine agonist (binds and activates dopamine receptors) that can quickly relieve motor fluctuations for a duration of time. Despite apomorphine working well to address OFF episodes, the injectable administration can be a challenge.

A novel administration of apomorphine is currently under review with the U.S. Food and Drug Administration (FDA). This dissolvable film containing apomorphine is applied under the tongue (sublingual) and could be approved by the FDA to treat OFF episodes in early 2019.Ultimately what’s needed are effective, fast-acting, more tolerable treatments that work for all types of OFF episodes that may occur throughout the day and that patients can use when they are in an OFF state. And just like maintenance levodopa, therapy should be tailored for each patient depending on their needs.

BUILDING TOWARD THE FUTURE OF PD TREATMENT

The primary aim of PD research is a cure, and this is a goal toward which scientists and clinicians continue to strive. Medical advances rely on both small and big leaps to ensure that patients are getting what they need now and to ensure that they can be hopeful for what is to come. PD is a complex disease, and its symptoms have a very real and significant impact on everyday life. Developing medications that truly meet these needs while continuing innovation with the patient in mind is imperative.

https://blogs.scientificamerican.com/observations/a-new-way-to-help-manage-parkinsons/