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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

Parkinson’s Medications May Cause Premature Ejaculation, Case Report Suggests

premature ejaculation

Antiparkinsonian medications may cause premature ejaculation in men with Parkinson’s, according to a case series that followed eight patients.

The study, “Acquired premature ejaculation in Parkinson’s disease and possible mechanisms,” was published in the International Journal of Impotence Research.

Premature ejaculation is a common male sexual dysfunction and can be a source of significant distress in men and their partners.

This dysfunction can be classified into lifelong premature ejaculation (LPE) and acquired, or secondary, premature ejaculation (APE). While with LPE, patients experience early ejaculation independent of sexual partners and starting in their first sexual encounters, those with APE develop early ejaculation after having previous normal ejaculation experiences.

Information on the prevalence of LPE and APE is scarce, and patient self-reports often conflict with clinician diagnosis.

Among the main causes of APE are sexual performance anxiety, psychological or relationship problems, and erectile dysfunction, as well as medical causes such as hyperthyroidism and prostatitis, or prostate inflammation.

Compared with men with LPE, those with APE are typically older, have a higher body mass index, and also have a greater incidence of hypertension and diabetes mellitus, among other conditions.

Sexual dysfunction is common in men with Parkinson’s, affecting 40.6-51.5 percent of them; however, these issues have not been studied in detail. Erectile dysfunction and premature ejaculation are the predominant forms of sexual dysfunction in this patient population.

The case series described eight men followed between 2008 and 2014 who attended a sex therapy specialist due to a new onset of premature ejaculation.

Patients’ mean age at Parkinson’s onset was 57.3 years and 62.6 years at study inclusion. Half had normal ejaculatory function before Parkinson’s diagnosis, while the remaining four experienced ejaculation within two to three minutes, though not regarded as problematic.

All patients reported a significant reduction in intravaginal ejaculation latency time (the time taken for a man to ejaculate during vaginal penetration) after Parkinson’s diagnosis.

Three patients experienced severe premature ejaculation, meaning that ejaculation occurred before penetration, while four reported ejaculation immediately following vaginal penetration. In addition, erectile dysfunction and/or altered sexual desire occurred in some of the patients.

Of note, all patients were taking anti-parkinsonian medications at premature ejaculation onset, including levodopa in two patients, dopamine agonist in three, and both in one patient. Azilect (rasagiline), amantadine, and an anticholinergic medication were also used.

Psychiatric medications included amitriptyline, Remeron (mirtazapine), and Zyprexa (olanzapine), taken by three patients. Four patients had hypertension, while ischemic heart disease, diabetes mellitus, hyperlipidemia (high cholesterol), benign prostate hypertrophy (enlarged prostate gland), and chronic heart failure were also reported.

“In this case series of [Parkinson’s] patients with APE, the ejaculatory dysfunction developed when patients were on antiparkinsonian medications, suggesting a possible medication effect,” the researchers wrote.

However, since premature ejaculation appeared a mean of four years after Parkinson’s onset, the authors also suggested that Parkinson’s progression may be an additional cause of premature ejaculation.

“Further research with a larger cohort is required on premature ejaculation in the constellation of Parkinson’s disease with a focus on the impact of Parkinson’s disease medications on the onset of premature ejaculation and the effect of anti-parkinsonian medication adjustment, as well as effects of available medications for premature ejaculation on the severity of this disorder,” the authors concluded.

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Source: Parkinson's News Today

#AAN2018- Inbrija Reduces Parkinson’s Off Periods, Phase 3 Trial Shows

Phase 3 Inbrija trial

Inbrija reduces Parkinson’s symptoms when standard treatments wear off, and decreases the length of these off periods, a Phase 3 clinical trial shows.

The therapy’s developer, Acorda Therapeutics, will present the results at the American Academy of Neurology annual meeting in Los Angeles, April 21-27. Parkinson’s News Today will be covering the conference.

Acorda’s presentation will be at 4:54 p.m. Pacific time on Tuesday, April 24. The title will be “Long-term Efficacy of Inhaled Levodopa in Parkinson’s Disease Subjects With Motor Fluctuations: a Phase 3 Open-Label Randomized Study.”

Inbrija (CVT-301) is a self-administered, inhaled version of levodopa intended to reduce the time when standard levodopa treatment wears off — periods known as off times.

Acorda conducted the Phase 3 trial (NCT02352363) to evaluate the safety and effectiveness of an 84-mg dose of Inbrija over 12 months in 408 Parkinson’s patients with movement problems.

The Inbrija group consisted of 278 patients. The other 130 were assigned to standard care. Only 204 of the patients who received Inbrija were able to complete the trial.

At the beginning of the study, the Inbrija group had a mean age of 63.6 years, had had Parkinson’s for nine years, were averaging 3.6 off periods a day, and were experiencing total off times of 5.6 hours per day. Patients took an average of 2.3 doses of Inbrija a day.

One of the measures that researchers used to measure Inbrija’s effectiveness was improvements in patients’ UPDRS-III scores, which assess both movement and non-movement symptoms, 10, 20, 30, and 60 minutes after dosing. Another measure was the percentage of patients able to regain control of their symptoms within 60 minutes of treatment.

Still another measure was reductions in patients’ off times. And a fourth was better scores on a scale known as PGIC, which shows whether a patient believes a treatment is effective.

A key finding was improvements in Parkinson’s symptoms at all time points between week 4 and 52 on the UPDRS-III scale.

Another finding was that patients were able to regain control of their symptoms within 60 minutes.

In addition, patients were able to reduced their total daily off times by between 1.32 and 1.42 hours. And 75 percent of patients showed improvements in PGIC scores.

Overall, improvements in UPDRS-III scores, daily off times and PGIC scores “support the efficacy of up to 52 weeks of treatment with CVT-301 (Inbrija) 84 mg in the treatment of off period symptoms,” the researchers wrote.

The results prompted Acorda to seek European Union approval of Inbrija as a treatment for off periods in Parkinson’s.

In addition to data from this Phase 3 trial, Acorda’s application to the EU included results of the Phase 3 SPAN-PD trial (NCT02240030) in 351 participants and the Phase 3 CVT-301-004E trial (NCT02242487) in 325 participants.

The U.S. Food and Drug Administration accepted Acorda’s New Drug Application for Inbrija in February 2018. It is expected to decide whether to approve it by October 5.

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Source: Parkinson's News Today