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24-hour Levodopa-carbidopa Intestinal Gel Lessened Dyskinesia, Parkinson’s Study Finds

dyskinesia, levodopa-carbidopa intestinal gel

A 24-hour treatment with a levodopa-carbidopa intestinal gel (LCIG) lessened the duration and functional effect of dyskinesia — involuntary, jerky movements — in Parkinson’s patients, according to a small study.

The research, “24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson’s disease,” was published in npj Parkinson’s disease.

Continuous intra-jejunal (the middle part of the small intestine) infusion with a LCIG has been shown to efficiently treat Parkinson’s motor fluctuations. The gel normally is administered with a portable pump directly into the duodenum or upper jejunum by a permanent tube inserted surgically.

Currently, it is mainly used as a 16-hour per day continuous infusion, and is licensed for use in this way. However, additional benefits have been observed when used as a continuous 24-hour infusion in the treatment of severe nocturnal akinesia (losing the ability to move muscles voluntarily), daytime falls and freezing of gait (FOG), as well as poor sleep quality.

Clinical trials have shown that a 16-hour treatment with LCIG can effectively reduce levodopa-induced dyskinesia (LID), which typically occurs after long-term therapy, despite an increase in daily levodopa dose. Current treatments options for LID, such as deep brain stimulation and Gocovri (amantadine, by Adamas Pharmaceuticals) are not uniformly available or are not suitable for all patients.

Researchers from Movement Disorder Unit at Westmead Hospital, in Australia, have now described their clinical experience with a 24-hour LCIG infusion to treat dyskinesia in Parkinson’s patients.

Of 74 patients treated with LCIG for motor fluctuations, 12 (10 men) were treated with 24-hour daily infusion intended to control troublesome daytime dyskinesia and with sufficient data pre- and post- initiation of continuous treatment. Patients’ mean age at the start of 24-hour LCIG was 69 years and mean duration of Parkinson’s was 18 years. Two had a mutation in the PRKN gene, whose mutations are associated with the juvenile form of Parkinson disease.

Among these 12 patients, four took 24-hour LCIG infusion due to lack of response to 16-hour therapy; two due to troublesome dyskinesia and levodopa-unresponsive FOG; three due to levodopa-unresponsive FOG with non-troublesome dyskinesia; two more had troublesome dyskinesia and nocturnal akinesia; and one self-initiated 24-hour therapy. Two transitioned from oral levodopa, without an in-between 16-hour infusion.

Patients’ clinical characteristics, as well as dyskinesia severity and incidence, were analyzed before and after therapy using the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) – part 3, part 4 (motor complications) total scores and sub-scores 4.1 (time spent with dyskinesias) and 4.2 (functional impact of dyskinesias). All evaluations were performed at baseline and at six months after starting 16- and 24-hour LCIG.

Daytime dyskinesia was reduced in nine patients (75%) following 24-hour therapy, including seven who were first treated with 16-hour infusion and the two patients who transitioned from oral levodopa.

Of the three patients without decrease in dyskinesia, one could not tolerate 24-hour infusion due to worsening of hallucinations and agitation, and shifted back to 16-hour therapy after two months. After six months, the patient’s neurocognitive function returned to baseline. A second 24-hour therapy was initiated 11 months later, but again led to no benefit. The remaining two patients had no change in dyskinesia despite eased FOG and nocturnal akinesia.

Combining the results from all 12 patients, both the time spent with dyskinesia and its functional impact were reduced during 24-hour LCIG treatment. In contrast, the MDS-UPDRS part 3 “ON” scores — control of motor symptoms — did not change.

Five patients showed lessened dyskinesia despite an overall increase in the total daily levodopa dose. No patient had worsened dyskinesia after a median follow-up of 27.5 months.

A total of three patients had worsening of nocturnal hallucinations, which diminished after lowering the night-time LCIG continuous rate. One patient developed asymptomatic peripheral neuropathy (nerve damage) within six months of 24-hour therapy, which remained stable during 18 months of follow-up.

Ten patients experienced vitamin B6 deficiency requiring supplementation, while seven developed vitamin B12 deficiency during therapy (16- or 24-hour). Two patients had hyperhomocysteinaemia (excess blood level of homocysteine), a condition associated with cardiovascular problems and neuropathy.

Of note, no patient elected to return to 16-hour infusion due to difficulty managing the pump, or technical difficulties with the jejunal tube.

Overall, if future studies confirm these findings, “24-[hour] LCIG may offer a novel approach to the treatment of troublesome dyskinesias which persist despite an adequate trial of 16-[hour] therapy,” researchers wrote.

Although further research is necessary to assess the mechanisms involved, the researchers hypothesized that the benefits with 24-hour treatment in patients not responding to 16-hour infusion may be due to continuous levodopa delivery to the brain.

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Exercise That Motivates Parkinson’s Patients to Push Limits Can Offer Range of Benefits, Experts Say

exercise in Parkinson's

With a treatment not yet within reach that might slow the progression of Parkinson’s disease, much less offer a cure, many — doctors, patients, and researchers alike — are looking to exercise in hopes of fending off a worsening of symptoms.

Interest in exercise-based interventions has risen so much that “the number of publications on exercise studies has increased by a factor of 10 since 2000,” Tanya Simuni, MD, chief of Movement Disorders in the Department of Neurology at Northwestern University, said in a 2016 interview on the International Parkinson and Movement Disorder Society website.

Many consider it common sense that exercise can help to compensate for the motor symptoms that mark Parkinson’s — and research points to this possibility — yet scientists still have few clues as to how exactly it does so.

Work done through the Parkinson’s Outcome Project, an ongoing study involving more than 12,000 patients in five countries, suggests that patients should exercise at least 2.5 hours each week to slow decline and maintain a better quality of life. A similar study advised that patients should begin regular exercise at diagnosis.

Still, this research stops short of recommending a specific exercise regimen as a best strategy.

This has led several enterprises — both for-profit companies and nonprofit groups —  to offer classes ranging from dancing to Parkinson’s-only boxing, and products such as specialized at-home exercise equipment that promise to reduce, reverse, and delay symptoms.

While the literature on exercise in Parkinson’s is “extensive,” Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson’s Disease Association and a practicing neurologist, told Parkinson’s News Today, studies on its effects are typically small. Only recently have they begun to grow in size and in quality — but “translating [their findings] into practical recommendations” is a challenge.

Exercise and the brain

In Parkinson’s, neurons in a brain area called the substantia nigra that are responsible for producing a neurotransmitter called dopamine gradually die off, leading to motor symptoms such as tremor and bradykinesia (slow movement).

Levodopa — which works to increase dopamine levels in the brain but cannot rescue damaged neurons — is currently the front-line treatment for the disease.

Some evidence suggests that, like levodopa, exercise may exert some of its effects by increasing dopamine. A recent study of 17 Parkinson’s patients used positron emission tomography (PET) scans of the brain before and after stationary cycling. Results showed that habitual exercisers in this group — eight patients who exercised more than three hours a week — had higher dopamine levels in the dorsal striatum (the brain area that receives dopamine input from the substantia nigra to help control movement) after stationary cycling than the nine others who were sedentary.

The eight exercisers also performed better on functional tests assessing motor symptoms, including the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 — which measures items such as gait and time to stand — and in tests of non-motor symptoms such as apathy and depression.

Exercise might also go a step further than levodopa by increasing brain-derived-neurotrophic-factor (BDNF), which promotes the survival of neurons that make dopamine — the same neurons that degenerate in Parkinson’s patients.

An analysis of 12 studies of BDNF levels in Parkinson’s patients found lower levels of BDNF in patients’ serum than in healthy individuals (mean difference of 2.99 ng/mL).

Two of these studies showed that patients who completed exercise programs lasting four, eight, or 12 weeks increased both serum levels of BDNF and UPDRS motor scores.

A separate review of 32 studies related to exercise’s effects on BDNF suggested that aerobic exercise increased BDNF serum levels in healthy people. This was seen to be both an acute effect of a single exercise session and a result of consistent exercise. Strength training did not impact BDNF.

Another Phase 2 study (NCT01506479) divided 128 recently diagnosed patients into three groups that either continued not exercising, participated in 30 minutes of gentle treadmill walking four times a week, or were assigned to six months of high-intensity treadmill exercises for 30 minutes four times a week. Those who did the high-intensity workout maintained the same UPDRS motor score at the study’s end as they had at its start, while those in group that did not exercise saw their scores drop by three points, and those who exercised minimally had a two-point drop.

Rock Steady Boxing

Rock Steady Boxing, a nonprofit, non-combat boxing program designed exclusively for Parkinson’s patients, aims to help all — regardless of skill level — take advantage of the benefits of exercise, while building a supportive and understanding community of patients.

Parkinson’s News Today columnist Jean Mellano, an athlete who not only boxes with Rock Steady but also does physical therapy, yoga, weight training, and daily walking to help treat her Parkinson’s, said “the camaraderie is off the charts.”

Joyce Johnson, Rock Steady’s executive director echoed that sentiment, noting “the magic of Rock Steady is the camaraderie and the fact that all of our boxers are fighting back against same disease.”

Founded in 2006, Rock Steady Boxing has grown in popularity and now operates out of more than 700 locations worldwide.

“We’ve actually had neurologists write Rock Steady Boxing on their little prescription pad and sent them to a location,” Johnson said.

Rock Steady allows affiliates to operate for a small fee in boxing gyms, YMCAs, hospitals, and churches. Some programs are free to patients thanks to grants, but most require participants to pay fees similar to that of an average exercise program.

A typical 90-minute class begins with a warm-up, followed by varied exercises designed to mitigate Parkinson’s symptoms through balance and flexibility work, jumping rope, weightlifting, and, of course, boxing.

A case study, listed on the group’s website and published in the journal Physical Therapyof six Rock Steady boxers showed that after 24-36 classes over the course of 12 weeks, all six boxers improved in at least five out of 12 outcome measures, such as the Functional Reach Test, gait speed, cadence, stride length, step width, and other measures of UPDRS part 3, as well as the Parkinson Disease Quality of Life Scale, an assessment of non-motor symptoms. Patients in earlier disease stages did better at 12 weeks, but those with more advanced disease gained benefits with regular classes that ran for 24 and 36 weeks.

Stephanie Combs-Miller, PhD, the case series’ lead author and an associate professor at the Krannert School of Physical Therapy at the University of Indianapolis, published a slightly larger study in 2013 comparing Rock Steady Boxing with a community-based exercise program that included stretching, resistance, aerobic, and balance-based exercises in 31 patients.

Patients again took part in 24-36 sessions of either workout over the course of 12 weeks. The researchers expected that both programs would lead to improvements, but that the boxers’ improvements would be more dramatic than those of patients in the traditional exercise program.

However, Combs-Miller and her team concluded that “both groups demonstrated significant improvements with the balance, mobility, and quality of life,” supporting the idea that any group-based exercise can help Parkinson’s patients, provided they do it consistently.

Still, as Johnson put it: “How much more fun is that for a grandpa to tell his grandkids that he’s going to boxing instead of saying he’s going to therapy?” 

Theracycle and forced exercise

Rock Steady boxers are encouraged by coaches and peers to attempt moves and workout intensities that seem to push the limits of their abilities.

The Theracycle takes this idea a step further, using a motor that forces patients to pedal the stationary bike faster than they could on their own, theoretically maximizing workout effects.

Jay Alberts, PhD, a biomedical engineer at the Cleveland Clinic and an avid cyclist, went on a 200-mile trip in 2003 on a tandem bike with a friend, who also happened to be a Parkinson’s patient. The friend was forced to pedal at Alberts’ pace, which was about 30 revolutions per minute faster than she would have been able to pedal on her own.  According to Alberts, her tremors disappeared during the ride and for a period of time afterward. 

Alberts brought another patient on his tandem bike and noticed similarly striking results. 

But requiring a strong cyclist to take patients out on tandem bike rides regularly is not a practical treatment plan for 10 million patients worldwide.

The Theracycle, a motorized stationary bicycle based on the exercycle invented in 1932, gives patients a safe way to engage in forced exercise — exercise where, in this case, a motor helps them pedal at a speed they wouldn’t be able to reach on their own — at home without a tandem bike or partner.

Alberts conducted a small study in 2009 at the Cleveland Clinic, which appears on the Theracycle website and was published in the journal Neurorehabilitation and Neural Repair, comparing the effects of forced exercise and voluntary exercise (in which patients choose the intensity at which they exercise) on Parkinson’s symptoms.

Ten patients were randomly assigned to complete three one-hour sessions per week of either voluntary cycling or forced exercise using a motorized cycle. After eight weeks, both groups showed improved aerobic capacity, but only the forced exercise group showed improvements (an average of 35%) on the UPDRS part 3.

Mike Studer, president and co-owner of Northwest Rehabilitation Associates, has been using the Theracycle in his Oregon physical therapy clinic since the company reached out to him more than eight years ago, shortly after the Cleveland Clinic study was published. He said he “remained skeptical” of the new research at first, but that the Theracycle “meets and exceeds” expectations.

His clinic also offers the Rock Steady Boxing program, yoga, treadmills, underwater exercises, and more. Studer says “a repetition is not equal to every other repetition.” With the Theracycle, he can control the intensity of a patient’s workout, a crucial factor in its effectiveness.

The main drawback of the machine is its price. It’s not covered by Medicare, and Rich Blumenthal, chief operating officer of Theracycle, admits that the $3,700-$5,900 price tag (depending on the model) can make the equipment difficult to sell. But patients’ lives “are just better when they start using this,” he says.

Both regimens have one thing in common — pushing patients to do more than they may think they are capable of doing.

“There is nothing wrong with people’s bodies. What’s wrong is that neurologically they quit producing dopamine,” Johnson said.

Whether they are encouraged by coaches or by motors, patients often end up doing more than they ever thought they could.

We may never know which exercise regimen is the most effective for preventing Parkinson’s decline, or which is better for any given patients.

“It’s virtually impossible to imagine testing every single modality versus every other modality,” Gilbert said, but “the answer is it’s probably a little of everything.”

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Dopamine May Prevent Movement Impairment in Parkinson’s Patients, Study Suggests

dopamine, movement impairments

Levodopa treatment can prevent movement impairment in patients with Parkinson’s disease by increasing overall sensory attenuation, or the ability to fine-tune information received from the senses before a motor action is performed, a study suggests.

Based on these findings, researchers suggest that dopamine, which increases as a result of levodopa treatment, may be important for regulating brain activity to effectively integrate predictions of action with sensory information — a process required for the control of voluntary movements.

“This may provide a common framework for understanding the role of dopamine in perceptual, cognitive, and motor function,” they wrote.

The study, “Sensory attenuation in Parkinson’s disease is related to disease severity and dopamine dose,” was published at the journal Scientific Reports.

Parkinson’s disease is often characterized by slower movements, which are associated with the impaired ability of patients to plan, initiate, and execute voluntary movements. However, the underlying mechanisms that promote these deficits are still not very well understood.

Researchers evaluated the sensorial and motor response of 18 patients with idiopathic Parkinson’s disease and 175 age and gender-matched healthy volunteers used as controls. All Parkinson’s patients were receiving treatment with levodopa, one of the main therapies used to increase the levels of dopamine.

To quantify participants’ sensorimotor response, researchers used the force matching task, in which a torque motor applies one of four force levels through a lever to the left index finger. Participants are then asked to match the force they just sensed either by pressing the lever with their right index finger (direct condition), or by sliding a linear potentiometer that controls the torque motor (slider condition).

In response to this test, people often apply a stronger force when exposed to the direct condition, while they tend to use a more accurately matched force in the slider condition. The overcompensation of forces that occur in the direct condition has been associated with the integrity of the fronto-striatal network — an area of the brain strongly affected by dopamine deficits in Parkinson’s disease.

Task results revealed that Parkinson’s patients had less sensitivity than controls. Still, the overall force response to matching the applied motor force was similar between patients and controls.

Further analysis showed that overall sensory attenuation was negatively related to Parkinson’s motor severity, but positively linked to individual patient dopamine levels, as measured by levodopa dose equivalent.

In general, patients who were taking higher levodopa doses were also the ones showing greater overcompensation on the direct condition of the task.

“These results support the hypothesis that dopamine alleviates disorders of movement in Parkinson’s disease by restoring the precision and hence the typical reliance on sensorimotor predictions,” the researchers wrote.

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Parkinson’s Patients Carrying Distinct Genetic Polymorphisms Less likely to Experience Levodopa–induced Dyskinesia, Study Shows

Polymorphisms

Parkinson’s patients carrying two types of genetic polymorphisms — a gene that has more than one variant in a given population — in the dopamine transporter gene are less likely to suffer from involuntary muscle movements associated with levodopa therapy, a study shows.

The study, “DAT gene polymorphisms (rs28363170, rs393795) and levodopa-induced dyskinesias in Parkinson’s disease,” was published in Neuroscience Letters.

Levodopa is one of the main therapies used to treat Parkinson’s disease. It works by replacing dopamine, a brain chemical produced by dopaminergic neurons that are destroyed gradually in the course of Parkinson’s.

Although levodopa therapy is often recommended to facilitate Parkinson’s symptoms’ management, the compound can have substantial side effects associated with its long-term use, including wearing-off effect (the medicine wears off before the patient can take the next dose), involuntary muscle movements, also known as levodopa-induced dyskinesia (LID), and changes in behavior (impulsive and compulsive behavior).

LID is one of the most common motor side effects of levodopa therapy — estimated to affect up to 95% of all patients taking levodopa for 15 years — and, at the same time, one of the most disabling.

Previous studies have proposed that Parkinson’s patients who are younger when they experience their first symptoms, have faster disease progression, and take higher doses of levodopa, are more likely to develop LID. However, given patients’ clinical variability to develop LID, these risk factors seem insufficient to explain its incidence, suggesting that genetic factors also may be involved.

Several studies have attempted to identify genetic factors that could increase patients’ susceptibility to LID, but results have been inconsistent so far. One particular gene, called dopamine transporter gene (DAT, also known as SLC6A3), might be an interesting candidate, because different genetic variants have been linked to different effects on dopamine uptake by neurons.

In fact, in Parkinson’s patients, homozygosity (same two copies of a given gene) for a specific form, or allele, of the DAT gene (called 9R) has been associated with an increased risk to develop the disease, whereas homozygosity for another allele, called 10R, has been associated with Parkinson’s protection.

Alleles are variant forms of the same gene (one copy of the gene inherited from each parent) that arise by mutation and are found at the same place on a given chromosome.

In this study, researchers aimed to determine whether different genetic variants of the DAT gene could be associated with patients’ risk to develop LID.

A total of 181 Italian Parkinson’s patients who had been taking at least 300 mg of levodopa daily for three years or more, were recruited. All patients were screened for two different genetic polymorphisms within the DAT gene: the rs28363170 (9R and 10R alleles) and the rs393795 (A and C alleles).

Data failed to reveal any significant difference in LID prevalence among patients who carried the two DAT genetic polymorphisms.

However, patients who possessed two copies of the 10R allele in the rs28363170 region and also carried the A allele in the rs393795 region, were less likely to develop LID in the course of long-term levodopa therapy, compared to patients who did not have these alleles.

“Despite this interesting result, our finding was obtained in an exploratory manner and thus need to be confirmed and replicated in different ethnic background populations and in larger cohorts of patients,” researchers wrote.

“Nevertheless, we believe that the identification of genomic biomarkers involved in drug response variability represents an important step in PD [Parkinson’s disease] treatment and it could be useful to identify patients more prone to better respond to treatments or to develop frequent and disabling conditions as adverse events like LID,” they concluded.

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Finding Balance with Medications

balance

What is my strategy?

I plan to take Parkinson’s disease (PD) medications as prescribed to get me to a point where I can function well and really push hard in my exercise. Then, I hope that a combination of exercise, diet, meditation, yoga, and massage will help me to deal with my PD progression and symptoms.

Currently, I take Sinemet (carbidopa-levodopa) 25/100, two tablets, three times per day. With my doctor’s guidance, I am weaning off a daily 4 mg Neupro patch. Sinemet has alleviated my internal tremors. However, I am still extremely fatigued all of the time.

Do I really believe the medications are helping?

I have never had any “aha!” moments as a result of taking medications. It was never like “wow, I feel so much better now.” I don’t experience the “off time” that some have when the meds are wearing off shortly before the next dosage is due. So, I question how much the medications are really helping me.

Why do I want to reduce or halt my PD medications?

Opioids target the brain’s reward system by flooding the circuit with dopamine. In the late 1990s, pharmaceutical companies reassured the medical community that patients would not become addicted to prescription opioid-based pain relievers. They were wrong — there is currently an opioid overdose crisis in the U.S.

Although opioids get more media attention, abuse of benzodiazepines (benzos) is equally rampant. Benzos create surges of dopamine in the body. Since their introduction in the 1960s, this class of medications, which includes Valium (diazepam), Ativan (lorazepam), and Xanax (alprazolam), have been widely prescribed to treat anxiety and insomnia, alcohol withdrawal, and other conditions. These medications must be prescribed with caution because they can be addictive.

Levodopa, a component of Sinemet, may improve PD symptoms because it causes the body to make more dopamine. Neupro (rotigotine) patches work by delivering the dopamine agonist rotigotine through the skin directly into the bloodstream. Rotigotine stimulates dopamine receptors in the brain. This, in turn, mimics the action of dopamine, which is found in lower-than-normal levels in the brains of Parkinson’s disease patients.

My conclusion

From my simplistic, high-level view, I see a common denominator (dopamine) in the three categories of the medications mentioned above. Even though my brain may not be functioning properly due to PD, taking drugs that impact the brain does not sit well with me.

What will be said about PD medications in the future? I am not sure I want to find out. This is why I am choosing to wean off as many of the PD drugs that I can. I want to continue to seek balance and to pursue my more holistic approach to diet and exercise to tame the PD dragon.

***

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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Eradication of Helicobacter pylori Infections Could Ease Gut Symptoms, Motor Dysfunction in Parkinson’s Patients, Study Suggests

Eradicating Helicobacter pylori infections could improve motor function, ease gut symptoms and increase levodopa’s effectiveness in Parkinson’s patients, according to a review study.
The research, “Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson’s Disease,” was published in the Journal of Parkinson’s Disease.
While a small subset of Parkinson’s cases have genetic causes, most cases are sporadic, with unknown environmental causes. Gastrointestinal symptoms such as constipation precede motor complications, suggesting that the disease might start in the gut and subsequently spread to the brain along the brain-gut axis.
This has been observed in rats, where injection of alpha-synuclein fibrils — the major component of Parkinson’s characteristic Lewy bodies — into the gut induced Parkinson’s-related pathology.
Chronic infections with H. pylori affect half the world’s population and may cause gastritis, ulcers, and stomach cancer, as well as various gastrointestinal symptoms. A greater occurrence of ulcers in patients with Parkinson’s was first reported in 1961. More recently, a link between H. pylori and Parkinson’s has been shown, with consistent reports of higher risk for Parkinson’s in people infected with this type of bacteria.
The research team reviewed all major studies that discussed the possible link between H. pylori and Parkinson’s, which led to four key findings:

Having Parkinson’s increases by 1.5 to 3 times the risk of H. pylori infection.
H. pylori infection worsens motor function in Parkinson’s patients.
Eradication of H. pylori with triple therapy improved motor function in Parkinson’s patients compared to infected patients in clinical studies.
Eradication of H. pylori improved gut absorption and increased plasma levels of Parkinson’s gold-standard treatment levodopa in patients. Research had shown that H. pylori binds to levodopa, preventing it from reaching the brain and reducing its effectiveness

As for pathways linking this bacterial infection with Parkinson’s, the researchers provided three possible explanations besides impaired levodopa effectiveness. One explanation is that bacterial toxins produced by H. pylori or alterations to the body’s own molecules such as cholesterol can damage neurons.
The infection can also cause a massive inflammatory response in the stomach, which would become systemic, cross the blood-brain barrier (BBB) — a semipermeable barrier that protects the brain — and worsen Parkinson’s symptoms and pathology. H. pylori could also reach the brain by colonizing immune cells that cross the BBB themselves.
Finally, H. pylori may disrupt the normal gut microbial population, or microbiota, altering inflammatory mediators that predispose a person to Parkinson’s disease.
“Our conclusion is that there is a strong enough link between the H. pylori and Parkinson’s disease that additional studies are warranted to determine the possible causal relationship,” David J. McGee, PhD, the study’s lead author and a professor at the Department of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, said in a press release.
Although current evidence suggests that “eradication of H. pylori or return of the gut microflora to the proper balance in [Parkinson’s] patients may ameliorate gut symptoms, L-dopa malabsorption, and motor dysfunction,” scientists still have little information on whether H. pylori infection “is a predisposing factor, disease progression modifier, or even a direct cause of [Parkinson’s]”, the authors wrote.
Specifically, future studies should explore the interactions of H. pylori with neurons and levodopa, the role of H. pylori toxins, how inflammatory responses to H. pylori may

Source: Parkinson's News Today

Chinese Compound Helps Reduce Levodopa-induced Dyskinesia, Eases Motor Symptoms in Parkinson’s, Study Finds

traditional Chinese compound

The traditional Chinese compound Zishenpingchan can be used as an add-on treatment to levodopa for improvements in motor symptoms and quality of life in patients with Parkinson’s disease, according to researchers.

The study, “Zishenpingchan granules for the treatment of Parkinson’s disease: a randomized, double-blind, placebo-controlled clinical trial,” was published in the journal Neural Regeneration Research.

Parkinson’s disease is a central nervous system disorder characterized by low levels of dopamine, causing tremors, stiffness, or slowing of movement.

The current standard for treatment is levodopa, which the body uses as a building block to make dopamine. But long-term treatment with levodopa can lead to abnormal, involuntary movements — a condition called dyskinesia — in more than half of treated patients.

As a result, there is a lack of treatments in Western medicine that can effectively and safely treat Parkinson’s in the long-term.

Several researchers have explored traditional Chinese medicine to find remedies that can help improve the quality of patients’ lives.

A Chinese professor, Jian-hua Hu, conducted a thorough clinical investigation into the effects of Zishenpingchan — a mixture of Chinese roots and herbs — in Parkinson’s disease.

In China, Zishenpingchan has been applied clinically to treat the disease and has been shown to improve patients’ dyskinesia and nonmotor symptoms, as well as delay disease worsening.

But to date, no clinical trials have been conducted to address the effects of the compound in a controlled environment.

Chinese researchers set out to evaluate the clinical efficacy and safety of this treatment in a clinical trial (ChiCTR-INR-1701194) in patients with Parkinson’s disease.

Researchers recruited 128 patients from the Department of Neurology of Longhua Hospital and Shuguang Hospital, affiliated with Shanghai University of Traditional Chinese Medicine in China.

Patients were already being treated with levodopa. They were randomized to either receive add-on treatment of Zishenpingchan granules or a placebo for 24 weeks. Researchers then evaluated the effects of the treatment across a variety of factors, including function, sleep, cognition, and quality of life.

First, researchers showed that administration of Zishenpingchan granules was significantly linked to a decrease in unified Parkinson’s disease rating scale (UPDRS) III score compared to patients treated with placebo, which suggests an improvement in dyskinesia and motor symptoms in treated patients.

While cognitive scores and experiences of daily living scores were not significantly different between the groups, depression and anxiety scores were significantly improved in the treatment group.

The UPDRS IV score, which measures motor complications, was significantly higher at 24 weeks compared to baseline in the control group, while the reverse was true in the treatment group. This suggests that Zishenpingchan granules reduces the severity of motor complications.

Additionally, quality of life, which was measured using the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), was significantly improved in the treatment group, suggesting treatment with Zishenpingchan improved patient’s quality of life.

And, the levodopa dosage had significantly increased at 24 weeks in the control group while there was no significant change in levodopa dosage in the treatment group.

Finally, researchers determined that all the adverse reactions to the treatment were mild, and no patients were lost due to the adverse reactions.

“This combination of Chinese and Western medicine has the potential to reduce levodopa dosages, and no obvious side effects were found,” researchers wrote.

These findings indicate that Zishenpingchan granules can help alleviate some of the symptoms of Parkinson’s disease, reduce toxic side effects of levodopa, and improve the quality of life of patients.

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Source: Parkinson's News Today

Ketamine Studied for Relief of Levodopa-associated Involuntary Movements

ketamine study

A Phase 1 trial will test the potential of ketamine — an analgesic medicine used for depression and pain — at reducing the uncontrollable, jerky movements that arise in Parkinson’s disease patients after long-term treatment with levopoda.

Levodopa, probably the most common treatment for Parkinson’s disease, is effective at improving the stiffness and slowness of movement that characterize the disease.

However, up to 40 percent of long-term users eventually experience dyskinesia, which is the uncontrollable and involuntary movements that may be restricted to certain parts of the body, such as head, arms or legs, or affect the whole body.

“The problem is levodopa works great for a few years — we call that the ‘honeymoon’ period — but then you start getting these side effects,” Scott Sherman, MD, PhD, a neurologist at the University of Arizona College of Medicine – Tucson, said in a press release.

The severity of dyskinesia varies among patients, with some experiencing small jerky movements and others being affected by strong, constant bursts. Unfortunately, these side effects go away only after a patient stops taking levodopa.

So, researchers at the University of Arizona will conduct a small Phase 1 clinical trial with 10 Parkinson’s patients to determine the potential of ketamine for rescuing levopoda-induced dyskinesia.

The trial follows earlier work by Sherman and Torsten Falk, PhD, the scientists leading the study. They were using ketamine to relieve pain in Parkinson’s disease patients when they noticed an unexpected effect — the treatment also reduced the patients’ uncontrolled movements. One patient was actually free of the jerky movements for several weeks.

The same results were seen in animal models, where treatment led to a significant reduction in abnormal involuntary movements. The reduction was sustained for three days, and 10 days passed before baseline involuntary movements returned.

Ketamine increases blood pressure, but may cause a sensation of “out-of-body” experience, also known as dissociation, Sherman said. “When people describe it, they have told me that they feel like they are in fish bowl,” said Sherman. Ketamine actually has been used as a psychedelic recreational drug, Sherman said, adding that researchers have established preventive measures and he is hopeful those side effects will not affect the clinical trial.

“We are going to monitor blood pressure closely to make sure it doesn’t get high,” Sherman said. “And we know at what dosage ketamine causes this disassociation; we expect that the dosage needed in Parkinson’s disease will stay well below that level.”

Parallel to the Phase 1 trial, researchers will undertake a rodent study to assess the mechanisms underlying the effects of ketamine in the brain.

“We want to find out exactly what ketamine is doing to have this effect,” Sherman added.

Positive results in both the human trial and the animal study could help researchers establish ketamine as a therapy for patients with Parkinson’s disease.

“Ketamine has been long overlooked. Now it could prove very useful for Parkinson’s patients,” Sherman said.

The Phase 1 human and the animal study are both supported by a $750,000 three-year grant from the Arizona Biomedical Research Commission.

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Source: Parkinson's News Today

Study Outlines Risk Factors for Frequent Falls in Parkinson’s Patients

frequent falls risk

Motor fluctuations, treatment with antidepressants, disease severity, and deep brain stimulation (DBS) are among the risk factors that contribute to frequent falls in patients with Parkinson’s, a large-scale study reports.

According to researchers, identifying predictors that put Parkinson’s patients at the greatest risk for falls can aid in early intervention to prevent these occurrences.

The study, “What predicts falls in Parkinson disease?” appeared in the journal Neurology: Clinical Practice.

Parkinson’s patients may experience falls as a result of their motor symptoms, such as uncontrollable accelerations, impaired balance, and freezing of gait. Approximately 50 percent of these falls require medical care.

Although a history of falling is considered the major risk factor for future falls, research reported that even individuals without any previous occurrences had a considerable risk of future falls. Other risk factors include disease stage and duration, older age, absence of tremor at rest, severity of motor impairment, cognitive dysfunction, taking antidepressants, and DBS — a surgical procedure to treat motor symptoms in Parkinson’s.

Recent studies also pinpointed dopaminergic treatment — intended to restore the reduced level of the neurotransmitter dopamine in Parkinson’s patients — disease severity, and gait characteristics, as well as clinical tests, as predictors of falls among patients without any previous history.

Researchers in this study analyzed longitudinal data from the National Parkinson Foundation Quality Improvement Initiative (NPF-QII) registry (NCT01629043) to discover what factors set apart Parkinson’s patients who are most likely to become frequent fallers.

The study included 3,795 participants from 19 NPF Centers of Excellence. A total of 3,276 (86.3%) patients reported no or rare falls in the three months prior to the first visit, of which 382 (11.7%) became frequent fallers by the annual follow-up visit. This rate is similar to those reported in prior studies, the researchers noted.

Predictors of falls included motor fluctuations, treatment with levodopa and antidepressants, DBS, reduced health-related quality of life, less than 90% of Parkinson’s diagnostic certainty, female sex, and worse semantic fluency (part of verbal fluency).

Another risk factor for falls was being a stage 2 or 3 on the Hoehn and Yahr scale — which is used to describe the progression of Parkinson’s symptoms, where stage 2 refers to bilateral involvement without impaired balance, and 3 to mild to moderate bilateral disease with postural instability but physical independence.

Regarding the association with antidepressants, the investigators said that although they are a known risk factor for falls in older adults and could indicate a greater incidence of depression — also a risk factor — clinicians should consider nonpharmacological alternatives to treat depression in Parkinson’s patients at risk of falling.

Between visits, factors contributing to conversion to “frequent faller status” included the addition of amantadine for involuntary muscle movements, a referral to occupational therapy, diagnoses of cancer or osteoarthritis, newly implemented DBS, and an increased need for social and hospital services, including more emergency visits, which may indicate poorer global health, the researchers said.

As for the correlation between DBS and the risk of falling, according to the authors, this finding is in line with evidence showing that postural instability and falls may worsen within the first year after surgery.

“We have identified a number of associations between disease characteristics, treatments, and comorbidities and emergent falls in [Parkinson’s],” they wrote. “Such identifiers may help target patient subgroups for falls prevention intervention.”

However, the scientists cautioned that although the analysis provides associations between risk factors and falls in Parkinson’s patients, it does not prove causality.

The NPF-QII registry is still recruiting participants for an estimated total of 10,000. It aims to identify the best expert care practices for improved outcomes, including survival and quality of life. The study is being conducted across the U.S., Canada, and in the Netherlands and Israel. More details on locations and contacts can be found here.

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Source: Parkinson's News Today

China Approves Neupro Patches to Treat Early-Stage Parkinson’s

Neupro, UCB, China

Neupro patches (rotigotine) have been approved in China for treating symptoms of early-stage idiopathic (of unknown cause) Parkinson’s disease as a stand-alone therapy or in combination with levodopa.

Patients may benefit from this treatment strategy over the course of the disease, through to late stages, when levodopa’s benefit wears off or becomes inconsistent.

UCB received an Import Drug License (IDL) from the China Food and Drug Administration, which opens a door for the availability of Neupro in the country. UCB now will proceed with launching Neupro so patients in China may benefit from the approval as soon as possible.

The availability of Neupro in China is testament to UCB fulfilling our commitment to provide additional value to patients around the world,” Jeff Wren, executive vice-president, head of UCB’s Neurology Patient Value Unit, said in a press release.

“We know the significant impact Parkinson’s can have on the lives of patients and their family members, and how important it is to effectively manage symptoms to allow patients to keep their independence and maintain their quality of life,” he said.

Wren noted that the company is “very excited” to make Neupro available to Parkinson’s patients in China, providing “a convenient treatment option to help them to manage their condition.

Estimates indicate that Parkinson’s affects approximately 3 million people in China.

Transdermal (through the skin) Neupro patches are designed to provide 24-hour continuous delivery of rotigotine through a once-daily application. After reaching the bloodstream, rotigotine binds to dopamine receptors in the brain, which mimics the effects of the neurotransmitter dopamine, which is found in lower-than-normal levels in the brains of Parkinson’s patients.

Prior studies have shown that Neupro patches improve motor function and the ability to perform daily living activities in Parkinson’s patients. Reported benefits include shorter duration of off periods, which are episodes when levodopa’s effects wear off, in patients with advanced disease.

In 2012, the U.S. Food and Drug Administration approved Neupro patches for the treatment of early- and advanced-stage Parkinson’s disease.

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Source: Parkinson's News Today