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Parkinson’s Foundation Opens Fellowship Program for Nurses Seeking Specialty

nurses

The Parkinson’s Foundation has established a first Parkinson’s Nurse Fellowship program in the U.S., offering one year of training and support to working nurses who want to specialize in treating people with this progressive disease.

Applications are being accepted through Feb. 20 for the fellowship, worth up to $95,000 each, from registered nurses or those with a bachelor of science in nursing who have at least five years of experience and are interested in a career in Parkinson’s disease (PD) care and research.

The four fellows selected will be notified by March 10, the foundation announced in a press release.

They will undergo a yearlong training and mentoring at one of two sites: Oregon Health & Science University in Portland,  and the Struther’s Parkinson’s Center in Minneapolis.  Each is a Parkinson’s Centers of Excellence, a global network of 48 clinical centers recognized for their high quality of care for those with this disease.

“We recognize the crucial role that nurses play in caring for people with Parkinson’s disease,” said John L. Lehr, president and CEO of the Parkinson’s Foundation. “From ensuring medications are administered on time to supporting the transitions of care, they are consistently on the front lines of the PD community.

“This fellowship provides them with a unique training opportunity to enter the Parkinson’s space equipped with knowledge and first-hand research experience.”

Each fellow will be assigned a mentor to guide their learning about Parkinson’s. Awardees will also receive clinical training, and be expected to identify and design a research project.

Following the fellowship, fellows will be given a $50,000 grant to pursue and complete their research project.

Applicants should expect to work in the United States after finishing their fellowship.

“With this fellowship opportunity, we want to build a community of Parkinson’s nurse experts who not only know how to offer the best treatment possible for people with Parkinson’s, but also contribute to research on Parkinson’s and the roles nurses play,” said Eli Pollard, the foundation’s vice president, and chief training and education officer.

More information about this fellowship program is available here.

An estimated 1 million people in the United States are living with PD.

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VCP, Enzyme in Protein Degradation, May Be Blood Biomarker of Early Stages of Parkinson’s, Study Suggests

VCP enzyme

Blood levels of valosin-containing protein (VCP) — an enzyme involved in protein degradation — may be used as a biomarker of preclinical and early clinical stages of Parkinson’s disease (PD), a study suggests.

Reduced levels of VCP in the blood were found in both animal models of the disease and untreated patients at preclinical and early clinical stages of Parkinson’s.

The study, “VCP expression decrease as a biomarker of preclinical and early clinical stages of Parkinson’s disease,” was published in the journal Scientific Reports.

Parkinson’s neurodegeneration begins many years before the emergence of its hallmark motor symptoms. It is thus crucial to identify biomarkers of presymptomatic, or preclinical, stages of the disease so that patients can benefit more from neuroprotective treatments, potentially preventing further damage.

The VCP enzyme, also known as p97 in mammals, has several cellular functions, including the maintenance of protein balance and quality. It is involved in the degradation of faulty proteins in several cellular compartments, including the mitochondria, known as the cells’ powerhouses.

Increasing evidence suggests that changes in VCP activity may contribute to the development of several neurodegenerative diseases.

Mutations in the VCP gene are responsible for the development of inclusion body myopathy with early-onset Paget disease and frontotemporal dementia, a condition that can affect the muscles, bones, and brain. VCP mutations also have been identified in people with other neurodegenerative disorders, such as Charcot–Marie–Tooth disease and amyotrophic lateral sclerosis (ALS).

Moreover, patients with neurodegenerative diseases and VCP mutations have been reported to show signs of Parkinson’s-like symptoms, including rigidity, tremor, and slowness of movements.

Together, the potential association of impaired VCP function with abnormalities in faulty proteins break-down, neurodegenerative conditions, and Parkinson’s-like symptoms suggest that changes in the enzyme may play a role in Parkinson’s development.

However, no studies have analyzed VCP levels during the early stages of idiopathic (sporadic) Parkinson’s — which is not caused by any mutations and is the most common form of the disease.

To learn more, a team of Russian researchers now evaluated the levels of VCP in a mouse model and in patients at the earliest stages of Parkinson’s.

The team analyzed VCP levels at different time points in both the blood and brain of mice injected with MPTP — a neurotoxin commonly used to induce the death of dopamine-producing neurons and create Parkinson’s models — that mimic early symptomatic stages of PD.

VCP levels also were measured in blood samples of 38 untreated and 14 treated patients with newly diagnosed Parkinson’s — considered to be early clinical stages — and in nine individuals with “predicted” Parkinson’s, considered late preclinical stages.

People with “predicted” Parkinson’s were those with an estimated PD diagnosis based on the presence of known predictors of the disease and who had a confirmed diagnosis two years later.

The researchers also analyzed blood samples of 23 people with neurological disorders other than Parkinson’s and 44 age-matched healthy individuals.

Data showed that VCP levels were similarly reduced in both mice and untreated patients at preclinical and early clinical stages of Parkinson’s disease.

The most significant changes in VCP levels observed in these mice were in the striatum and substantia nigra, two brain regions involved in Parkinson’s. Notably, after a significant reduction in VCP levels in these regions, there was an increase of VCP levels during the late presymptomatic stages, which the researchers hypothesized may be associated with compensatory mechanisms.

Changes in the enzyme levels in the substantia nigra were accompanied by similar alterations in the blood, suggesting that VCP blood levels “can be considered as biomarkers of the neurodegeneration of PD,” the researchers said.

In addition, untreated patients and people with “predicted” Parkinson’s had significantly lower VCP levels — by nearly two-fold — than healthy people. No significant differences were found between treated patients, people with other neurological diseases, and healthy volunteers.

These findings highlighted that a reduction in VCP levels is associated specifically with the development of Parkinson’s, and occurs in late preclinical and early clinical stages of the disease. It also showed that treatment influences the enzyme levels in Parkinson’s patients.

“These data suggest that a decrease in the relative levels of [VCP] might serve as a biomarker for the development of [disease] at the early clinical and preclinical stages of human PD [Parkinson’s disease],” the researchers said.

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Data in Online Fox Insight Surveys Similar to Traditional Efforts in Parkinson’s, Study Finds

Fox Insight study

People with Parkinson’s disease taking part in the Fox Insight study, where they self-report details about their illness, share similar clinical and demographic features with patients brought through more traditional ways into large data studies, researchers found.

This finding suggests that groups recruited exclusively online can be useful to Parkinson’s research — although they may have drawbacks that need to be addressed.

The study, “Comparison of an Online-Only Parkinson’s Disease Research Cohort to Cohorts Assessed In Person,” was published in the Journal of Parkinson’s Disease

The Fox Insight (FI) study, launched by the Michael J. Fox Foundation, aims to collect large amounts of self-reported data about the health experiences of adults with and without Parkinson’s. Healthy people are serving as a control group.

This study’s recruitment is done online — a departure from more traditional models that usually require participants to travel to a hospital or academic center for interviews and/or exams.

As such, meaningful differences might exist between those willing or able to participate in online and in-person trials.

Researchers compared individuals with a self-reported Parkinson’s diagnosis in the FI study to those taking part in three other traditional (in-person) studies: the Parkinson’s Progression Markers Initiative (PPMI), the Parkinson’s Disease Biomarker Program (PDBM), and the idiopathic PD LRRK2 Consortium (iPDLC). With this last study group, only individuals without LRRK2 mutations — one of the most common genetic causes of Parkinson’s — were included.

Comparisons were done involving a total of 12,654 people participating in FI study, 422 in PPMI, 700 in PDBP, and 508 in iPDLC. (To date, more than 43,450 people are enrolled in Fox Insight. Researchers here looked at those whose data seemed consistent with an established diagnosis, including reporting of results from tests like the Movement Disorders Society-Unified Parkinson’s Disease Rating scale (MDS-UPDRS) II.)

“In general,” wrote the researchers, “we found that the FI cohort is comparable to the other cohorts.”

For example, no significant differences in any recorded motor symptoms were seen between the FI and the PDBP or iPDLC patient groups (cohorts).

Some motor symptoms, however, were more common among people in the FI than PPMI studies. These included difficulty turning in bed (47.22% vs. 25.59%), problems with walking and balance (59.45% vs. 36.73%), and freezing of gait (19.28% vs. 4.74%). The researchers noted that comparisons here were limited to 4,072 people from Fox Insight, all diagnosed in two or fewer years, because the PPMI study only included people diagnosed within two years of enrollment.

Non-motor symptoms also tended to be similar between the FI and other cohorts. Again, however, there were a few differences.

For instance, the groups reported differences in the frequency of REM sleep behavior disorder, but these frequencies also varied depending on what metric was used in the different datasets. As such, it’s not clear to what extent this reflects actual differences and to what extent it’s just differences in the taking of measurements.

Indeed, FI’s reliance on self-reporting was a consistently addressed limitation. For example, in terms of assessed cardiovascular risk factors, the FI cohort reported significantly higher rates of high blood pressure (43.3% vs. 27.49%) and high cholesterol (47.28% vs. 21.8%) than was seen among people in the PPMI cohort.

“Self-reported medical history, and especially cardiovascular history, is particularly prone to inaccurate reporting,” the researchers wrote, adding “the accuracy of self-reported PD” is an issue “we are currently not able to directly assess.”

But, “it is [also] possible that the FI cohort allows for participation of individuals with medical comorbidities that might otherwise be excluded from other, in-person observational studies” or because of more advanced disease states.

In other words, such differences in data collected might be due to inaccurate self-reporting, or it might be reflective of actual differences between these patient populations. Future studies may be necessary to know for sure.

Likewise, a similar frequency in the use of medications like levodopa — a mainstay of Parkinson’s treatment — was seen among these various study cohorts, but use of other medications — like dopamine agonists — were significantly more common in the PDBP than FI cohorts (49.07% vs. 32.08%).

This finding “could indicate either differences in prescribing trends, or rather an under-reporting of use of non-levodopa agents in FI,” the researchers wrote.

It should also be noted that, in some regards, the similarities seen between the FI and other patient groups weren’t necessarily ideal. “PD research studies are lacking in gender, ethnic, and racial diversity, with a significant over-representation of males and whites,” the researchers said.

Although the proportion of females was comparatively high in the FI cohort (45.56%), the vast majority (96.85%) were white, as were more than 90% of people taking part in the other Parkinson’s data studies. Most, more than four-fifths, had also completed at least some schooling beyond high school.

This suggests a continued need for efforts to increase diversity, particularly ethnic and socioeconomic diversity, in these studies, since a representative sample is by definition necessary to get a realistic understanding of the disease. Efforts aimed at increasing diversity are underway in the FI study.

Despite potential limitations, this study suggests that the online recruitment and self-reported data of FI patient group is collecting information of relevance to Parkinson’s  that is reasonably similar to data on patients who participated in in-person studies.

“The results of this analysis indicate that research utilizing data from an online-only self-reported PD cohort is feasible, and that a cohort assembled in this way has features that are broadly similar to cohorts recruited in person,” the researchers wrote.

“By following a PD population unprecedented in size and scope, the FI cohort can therefore serve to further our understanding of the frequency, severity, and progression of symptoms and quality of life in PD,” they concluded.

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Number of Dopaminergic Neurons at Birth Could Affect Lifetime Parkinson’s Risk, Report Suggests

Dopaminergic neurons at birth

The number of dopamine-producing (dopaminergic) neurons at birth could influence a person’s lifetime risk of developing Parkinson’s disease, according to a group of experts.

Because these nerve cells die over the course of the disease, having fewer of them to begin with could translate to a higher risk, the scientists said.

Their report, “Does Developmental Variability in the Number of Midbrain Dopamine Neurons Affect Individual Risk for Sporadic Parkinson’s Disease?” is a review of scientific literature on the topic. It was published in the Journal of Parkinson’s Disease.

Parkinson’s is a progressive neurodegenerative disease, meaning that it steadily worsens as neurons die over time. The hallmark of Parkinson’s is the loss of dopamine — a neurotransmitter crucial for coordinating movement and regulating mood — that occurs when dopaminergic neurons in a brain structure called the substantia nigra malfunction and die.

The substantia nigra communicates with a neighboring brain structure called the striatum and it is believed that the loss of dopamine and dopaminergic neurons in these structures must cross a certain threshold before the symptoms of Parkinson’s become noticeable. The number of dopaminergic neurons an individual is born with, therefore, might influence how soon this threshold is reached.

Precisely how many of these neurons must die before symptoms appear remains an open question. No datasets of nigral (belonging to the substantia nigra) dopaminergic neuron counts are available for individuals with recent onset of Parkinson’s symptoms.

Nor is there a strong scientific consensus regarding the number of dopaminergic neurons in normal substantia nigra. Different methods for marking both dopaminergic neurons and age-related changes that can limit the number of functional neurons within the brain hinder precise counts.

To estimate the variation in dopaminergic neuron numbers across people, a team of scientists now examined the data in four previous studies. Each study followed strict exclusion criteria, such as not admitting patients with histories of neuropsychiatric disease and/or other neurological damage.

The studies are: Ageing of substantia nigra in humans: cell loss may be compensated by hypertrophy, published in 2002; The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson’s disease estimated with an unbiased stereological method, published in 1991; Unbiased morphometrical measurements show loss of pigmented nigral neurones with ageing, published in 2002; and Morphometry of the human substantia nigra in ageing and Parkinson’s disease, published in 2008.

In the review, the researchers focused on individuals who died before their 51st birthday, to minimize the risk that any observed variation was due to age-related effects, or to undiagnosed progressive disorders.

The studies showed a wide variation between individuals — ranging from 147% to 433% — in terms of the difference between those with the most and the fewest dopaminergic neurons. Such variation must be better understood to properly understand its significance, the researchers said.

Many of the genes implicated in rare developmental abnormalities in humans also are involved in determining the location, formation, and size of the dopaminergic neuron population. Based on past studies, the researchers suggest that subtle changes in how active these genes are throughout development likely determine the variation witnessed between individuals.

Although clearly defining these changes poses a significant challenge, some clues are emerging.

One recent study, for example, linked Parkinson’s risk to single nucleotide polymorphisms (SNPs) — changes of one single letter of the genetic code — that affected gene regulatory elements involved in early nervous system development. This, in turn, affects the number of neurons an organism has.

Other studies have shown that Parkinson’s-related mutations also can reduce the number of dopaminergic neurons capable of being grown in the lab.

The alpha-synuclein protein plays a well-documented role in Parkinson’s progression. Its role in early development is less understood. One mouse study showed that the expression of the alpha-synuclein gene could affect the number of dopaminergic neurons in the substantia nigra. This suggests that, beyond the pathogenic role it plays in Parkinson’s, alpha-synuclein may help determine the early development and survival of dopaminergic neurons.

Non-genetic factors also appear to impact dopaminergic neurons by affecting critical periods of brain development. These factors include viral infection, exposure to environmental toxins, and hypoxia (low oxygen) at birth.

Based on the information collected throughout their review, the researchers propose that the number of nigral dopaminergic neurons individuals are born with and that survive immediately following birth affects their lifetime risk of developing Parkinson’s disease.

However, the researchers note that current knowledge of the factors influencing the development and survival of dopaminergic neurons is incomplete.

Therefore, “we need to explore the changes that occur both during development and during adulthood and aging when we seek to understand the full landscape of [Parkinson’s] risk,” they said.

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Help Us Improve Our Site!

We are always trying to provide a better, more relevant website to meet the needs of our readers. The best way to do that is to hear from people like you.

We’ve partnered with Think Company, a research and design firm, to schedule one-one-one phone interviews with patients and caregivers starting the week of January 27th. Participants will receive $75 gift cards for an hour of their time. We are looking specifically for rare disease patients and caregivers. 

If you’re interested, please take this quick, secure survey (1-2 minutes) and tell us about yourself so that we can reach out to you to schedule your session. We hope you participate!

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This is the link to the survey: https://www.surveymonkey.com/r/LZQ7K7V

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Stimulating Blood Vessel Growth in Brain with FGF1 May Hold Promise as PD Treatment, Company Says

FGF1

Stimulating the growth of blood vessels in the brain through the use of fibroblast growth factor 1 (FGF1) may hold promise as a strategy for treating Parkinson’s disease, according to a white paper released by Zhittya Genesis Medicine (ZGM). Clinical trials testing this theory are being planned.

The white paper is titled “Parkinson’s Disease: Therapeutic Angiogenesis as a Disease Modifying, Breakthrough Therapy?”

The exact cause of Parkinson’s (PD) has long been unclear. One hypothesis that has gained traction in recent years is that the neurodegenerative disease could be, in essence, a disorder of blood flow.

Cells in the brain require a lot of nutrients and oxygen; as such, getting proper blood supply into the brain is necessary for these cells to function and survive. In Parkinson’s, dopamine-producing neurons in the brain die off. This hypothesis posits that the reason for this is limited blood flow to these neurons.

Studies using functional magnetic resonance imaging (fMRI) — which detects changes in blood flow — have suggested that blood flow in people with Parkinson’s is indeed restricted, by as much as half, in areas of the brain that are damaged by the disease. Such studies have lent credence to this theory.

If this hypothesis is correct, “then it would make sense that if you could restore blood flow to the brain by re-establishing the microvasculature, progression of the disease could be halted or even reversed,” the researchers said.

As a therapeutic strategy, this idea is called therapeutic angiogenesis. Angiogenesis refers to the growth of new blood vessels.

“Over the last three years, we have continually uncovered data which strengthens our theory that Therapeutic Angiogenesis might be a viable breakthrough treatment for Parkinson’s disease,” Daniel C. Montano, ZGM’s CEO, said in a press release. “If, as we believe, Parkinson’s disease is caused by micro-vascular disruption in the brain, we are hopeful that our molecule can do in the brain, what it has already demonstrated it can do in prior US FDA clinical trials in heart disease patients, namely, grow new blood vessels.”

The molecule noted by Montano is FGF1, a signaling protein that plays a number of roles in the normal functioning of the body. Critically, FGF1 is a powerful stimulator of angiogenesis — but only in tissue that has been damaged or oxygen-starved.

Cells in such tissues increase their expression of the receptor for FGF1 by as much as 100-fold. This makes such tissue more sensitive to the angiogenesis-inducing signals from FGF1. Because of this, applying a therapeutic dose of the molecule to such damaged tissue would be “like throwing a match in a dry stack of hay,” the researchers said.

Importantly, this also means that the effects of FGF1 on healthy tissue elsewhere in the body are expected to be minimal.

Preclinical studies have supported the potential efficacy of FGF1 in Parkinson’s. For instance, monkeys with modeled Parkinson’s demonstrated improvements in motor function following infusions of FGF1. Evidence also showed the growth of new dopamine-producing neurons in these monkeys, suggesting that the treatment was actually reversing some of the damage.

“In previous studies conducted with monkeys, our drug demonstrated a genuine disease modifying effect as it successfully regenerated new dopamine neurons in the brain, which, we believe, led to the restoration of the animal’s motor skills,” said Jack Jacobs, PhD, ZGM’s president.

Of course, whether such treatment will be beneficial for humans will require testing in clinical trials.

The compound has shown promising results outside of the brain in Phase 2 trials “in treating a number of medical disorders characterized by a lack of blood perfusion, including coronary artery disease, diabetic foot ulcers and venous leg ulcers,” the researchers said.

Now, ZGM is planning a Phase 1 trial of FGF1 in Parkinson’s; the white paper outlined the basic trial design.

The plan for the initial “proof of concept” study is to administer hour-long infusions of FGF1 to participants with Parkinson’s five days per week for six weeks. Three doses of FGF1 that have demonstrated a good safety profile in the preclinical studies cited by ZGM will be tested. There will be no placebo group.

Safety and efficacy will be monitored, with monthly follow-up visits continuing for a year.

The trial is planned for a 2020 launch at locations in the United States, Mexico, and Estonia. ZGM recently filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration, which is required in order to get regulatory approval for most human clinical trials.

“We believe we may have a breakthrough therapy for this disease, which is why we are continuing to contribute millions of dollars and other resources toward this vital R&D work,” Jacobs said, adding, “We are looking forward to applying this same treatment [which showed efficacy in monkeys] in human clinical trials.”

ZGM said anyone wishing to obtain a copy of the white paper may email the company at dan@zhittyamedicine.com.

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Dance with Parkinson’s Program Inspires Alumni to Spearhead Classes at Louisiana Tech

In keeping with a burgeoning emphasis on exercise in Parkinson’s, Louisiana Tech University (LTU) has launched a dance program to help patients manage the disease.

Called Dance with Parkinson’s, the program begins Feb. 5 at LTU’s Lambright Sports and Wellness Center. The goal is to get patients moving at their individual level of comfort — and to have fun doing it.

“Dance encompasses many of the same physical challenges and benefits of exercise,” said Gretchen Jones who, along with business partner and fellow LTU alum Leaia Alsup, recently finished a two-day benefactor-funded training course at the Mark Morris Dance Center. The two will be program instructors.

The tailored workshop was 16 hours of hands-on teaching plus practical training to help prepare Jones and Alsup to lead classes and build a program, according to an article on LTU’s website.

“I had only a very basic knowledge of Parkinson’s before becoming involved with this program,” Jones said. “I didn’t truly realize how difficult day-to-day activities can be for patients with Parkinson’s. I understand more clearly now that having Parkinson’s alters a great many things, from physical challenges to social challenges. Dance has tremendous power to connect people and bring joy to all.”

The program was set in motion following a 2018 campus visit by another LTU graduate, Kelly Harp Haber, who is lead dance instructor for the Dance for Parkinson’s program in New Orleans. Dance for Parkinson’s offers classes for patients in more than 250 communities in 25 countries.

In town to teach at Twin City Ballet Company, Haber stopped by the university’s Rock Steady Boxing program for Parkinson’s patients and was so impressed that she wrote LTU’s president, Les Guice, about it. “The magnitude of the work that is happening in that class is remarkable,” she wrote, adding that although she taught a variety of ballet classes, the “crown jewel” of her work is her weekly Parkinson’s dance class.

Guice wrote back that he loved the idea of bringing new activities to the school’s newly founded Parkinson Resource Center, which aims to promote a healthy Parkinson’s community through programs, ideas, and resources. That correspondence, and behind-the-scenes work by faculty members Donna Hood and Tara Haskins, led to the university’s Dance with Parkinson’s program.

To emphasize the program’s benefits, Haber recently gave the university two sample classes.

What’s key to the program is that participants have an artistic and aesthetic experience that incorporates exploration, visualization, and socialization, Jones said. The LTU program will also introduce Louisiana themes in addition to the dance classics.

“After learning about the disease and learning that dance and movement can help with [patients’] everyday life, I just want to help,” Alsup said. “I just want to offer what I know and give them a place or opportunity to move in.”

Because Parkinson’s patients generally experience motor and cognitive impairment, as well as mood changes and social isolation, dance may positively affect their quality of life, according to the International Parkinson and Movement Disorder Society.

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Cannabidiol Found to Reduce Anxiety-induced Tremors in Parkinson’s Patients, Study Shows

Cannabidiol (CBD)

A single dose of cannabidiol (CBD) can decrease anxiety and tremor strength in people with Parkinson’s disease during situations known to induce anxiety, such as a public speaking exercise, a study found.

The results of the study, “Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson’s disease,” were published in the Journal of Psychopharmacology.

Cannabidiol — and the different molecules found in the Cannabis sativa plant — has attracted much attention since its widespread legalization. One of the main components of the plant, CBD does not have psychoactive properties, unlike tetrahydrocannabinol (THC), the main hallucinogenic component of cannabis.

It does have anxiolytic, or anxiety-reducing properties.

Given that, and due to its anti-inflammatory and neuroprotective properties, CBD has been studied for use in a number of conditions, namely epilepsy — where it is approved to treat certain types of the disorder — inflammatory diseases, cancer, psychiatric disorders, and neurodegenerative diseases.

CBD also has been tested in a number of anxiety studies and has previously been shown to decrease anxiety in healthy volunteers. Now, researchers tested the potential of CBD as an anti-anxiety treatment for people with Parkinson’s.

In addition to motor symptoms, such as tremors and freezing, Parkinson’s also is characterized by several non-motor symptoms, including anxiety. Around 67% of people with the neurodegenerative disease have reported this symptom, with anxiety-inducing situations aggravating their Parkinson’s tremors.

The anxiety treatments currently available, such as selective serotonin inhibitors — the most commonly prescribed antidepressant — and benzodiazepines, have side effects which aggravate Parkinson’s symptoms.

The researchers say better options without side effects are needed for treating anxiety, especially in the elderly and in this particular patient population.

So far, cannabidiol has been described as safe, and seems to have very few side effects, making it a good prospective treatment option. However, scientists say more studies are necessary to evaluate CBD, as it is crucial to confirm that the treatment does not interact with other parkinsonian medications.

To learn more, a team of Brazilian researchers conducted a clinical trial in which 24 people with Parkinson’s disease, mean age 64.13 years, took a single, 300 mg dose of CBD or a placebo 90 minutes before being asked to do a public speaking test. This is a common way of inducing anxiety in an experimental setting. The participants had to give a talk on a subject such as “transportation in their city” and were recorded while doing so. They were told that the videos would be analyzed by a psychologist.

The participants all reported the onset of Parkinson’s symptoms after age 50, and had a mean disease duration of 6.5 years. Most individuals were taking levodopa (19 patients) as well as other medications.

All of the patients took part in two experimental sessions within a 15-day interval, during which their blood pressures, heart rates, tremors, and moods were measured at different time points.

The scientists found that the amplitude of tremors was significantly lower in patients who received cannabidiol compared with placebo — and CBD also significantly reduced the anxiety level. There were no differences in any of the other measurements between the CBD and placebo groups.

“These observations suggest that CBD may be an alternative treatment for patients with PD and anxiety,” the researchers said.

CBD’s mechanism of action is not well-understood, since it has many different targets in the brain. Two targets, serotonin 1A receptor (5-HT1A) and cannabinoid receptor type 1 (CB1), have previously been linked to anxiety. As such, the researchers said the interaction of CBD with 5-HT1A and CB1 could in part explain how the compound might be working.

The investigators noted that the study has several limitations. One was its small size — only 24 people participated, 22 of whom were men. In addition, the speaking test was done just 90 minutes after taking CBD. More time might have been needed to see the full effect of the treatment, they noted. The study also lacked active comparators for CBD, such as other anti-anxiety therapies.

Despite these drawbacks, the initial results are promising enough to warrant further investigation into how CBD works in the brains of Parkinson’s patients, the researchers said.

“This is the first study that shows the anxiolytic effects of CBD in patients with PD and its ability in attenuation of the tremor amplitude in anxiogenic situations,” they said.

The investigators suggest future experiments should include more patients and different doses of cannabidiol, for example, having participants take CBD every day instead of in a single dose. Further research is necessary to confirm the calming effects of CBD and what quantity and frequency is optimal for the best results in people with Parkinson’s, they said.

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Medicine Long Used for Respiratory Ills Seen to Help Parkinson’s Patients in Small Trial

Parkinson's study results

A medicine approved in the late 1970s to clear the respiratory tract and thin mucus can also cross the blood-brain barrier and possibly protect cells there from the damage seen in Parkinson’s disease, a small Phase 2 clinical trial has found.

The study detailing these results, “Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations – A Nonrandomized, Noncontrolled Trial,” was published in JAMA Neurology.

Mutations in the GBA gene are one of the most common genetic risk factors for Parkinson’s. The GBA gene contains instructions to produce an enzyme, called beta-glucocerebrosidase (GCase), that is active in lysosomes — special compartments within cells that break down and recycle different types of molecules.

When the GCase enzyme fails to work as it is supposed to, toxic substances like abnormal alpha-synuclein accumulate inside dopamine-producing neurons, leading to the inflammatory and neurodegenerative processes that are observed in Parkinson’s.

In theory, boosting GCase activity through the “repurposing” of this medicine could slow disease progression.

Repurposed medicines are those approved to treat diseases other than that now under study (in this case, Parkinson’s). Because their mechanisms of action and safety are known to differing degrees, the expensive and lengthy process of discovering and testing a new compound is typically not necessary.

Ambroxol (brand names are Mucosolvan, Mucobrox, and Mucol, among others) has been used worldwide for decades to treat respiratory diseases associated with sticky or excessive mucus, and is known to boost beta-glucocerebrosidase activity.

But for it to work in the context of Parkinson’s, it needs to reach the brain and central nervous system. This means it needs to cross the blood-brain barrier, the semi-permeable membrane that protects the brain from the external environment. This barrier often blocks medicines from being carried into the brain.

Researchers at the University College London Institute of Neurology designed an open label, Phase 2 trial (NCT02941822) to test ambroxol in Parkinson’s patients at a single center, evaluating its safety, tolerability and pharmacodynamics (how the body affects a medicine) in people with and without GBA mutations.

Twenty-four patients, all with moderate, idiopathic Parkinson’s and on “dopaminergic therapy” were enrolled in the study; 17 completed the six months of treatment and required tests. Most withdrew due to discomfort or complications with the lumbar puncture used to collect cerebral spinal fluid (CSF).

These 17 people — eight with GBA mutations and nine without GBA mutations; average age of 60 — were given a daily dose of oral ambroxol that gradually escalated from 120 mg (60 mg three times a day) to 1.26 grams (420 mg three times a day).

Clinical examination and blood testing were performed on day 11, and at three months, six months and nine months after starting the treatment. Cerebrospinal fluid samples were collected via lumbar puncture at the study’s beginning and end. Five patients also underwent a third puncture for spinal fluid collection nine months after treatment initiation.

The study’s primary goal, in addition to safety, was to assess ambroxol’s ability to cross the blood-brain barrier and to change beta-glucocerebrosidase’s activity in the brain. This was determined by measuring beta-glucocerebrosidase and ambroxol levels in patients’ blood and CSF after six months of treatment.

A significant increase of 156-ng/mL in ambroxol levels in the cerebral spinal fluid was seen at this point, indicating the therapy could cross the brain-blood barrier to reach the central nervous system. Its use was also found to be well-tolerated, without any serious side effects reported.

“This finding is important, as the administered dose was approximately 10 times higher and was administered for a longer duration than specified in its license,” the researchers wrote.

People with Parkinson’s are known to have lower levels of alpha-synuclein in their CSF than others. This may be the result of compensatory mechanisms that cells use to sequester toxic soluble alpha-synuclein, studies suggest.

After six months of ambroxol’s use, the concentration of alpha-synuclein in patients’ cerebral spinal fluid rose by 13% (an increase of 50 pg/mL) and beta-glucocerebrosidase protein levels in the CSF by 35% (an increase of 88 ng/mol). These changes underscored the therapy’s neuroprotective effect, the researchers wrote.

“The increase in total CSF [alpha]-synuclein concentration implies, based on previous in vitro and in vivo data, that ambroxol has also had an association with [alpha]-synuclein metabolism,” they said.

Compared to the beginning of the study and in line with previous research, the increase in alpha-synuclein was accompanied by a 19% decrease in beta-glucocerebrosidase’s enzymatic activity.

Ambroxol’s use also did not “aggravate motor symptoms,” the study reported, and may have helped to ease them in all treated patients (those with and without GBA mutations).

These results suggest that ambroxol can cross the blood-brain barrier and increase beta-glucocerebrosidase levels in tissues, meaning the enzyme may be able to counter the abnormal build-up of alpha-synuclein in the brain of  people with Parkinson’s, stopping or slowing it from becoming toxic to brain cells.

“Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD [Parkinson’s disease],” the team concluded.

The Cure Parkinson’s Trust also reported on this study and its findings on its website.

“By using a drug which has shown to reduce the build-up of alpha-synuclein, and which also has a long and well-understood safety record, it is hoped that we might have a candidate for long term use that will reduce or even halt the progression of the disease,” the Trust wrote.

Larger trials are necessary, the U.K. group wrote.

“As Ambroxol is already approved as a drug … if a larger trial is successful, this drug would be readily accessible and could be seen as a treatment to slow down Parkinson’s within a short time-frame. This would have a huge impact on the lives of many people living with Parkinson’s today.”

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International Group Reflects on Decade Of Collaborative Parkinson’s Genetics Research, Notes Future Plans

IPDGC progress, future

A decade after its founding, the International Parkinson Disease Genomics Consortium (IPDGC) is looking back on on its first 10 years of research and outlining its goals for the future.

IPDGC was started in 2009 by a small group of researchers who thought that collaborative efforts were necessary to further understanding of the genetics of Parkinson’s disease (PD).

The group has now published a paper, titled “Ten Years of the International Parkinson Disease Genomics Consortium: Progress and Next Steps,” in the Journal of Parkinson’s Disease, in which they reflect on the progress they’ve made and where they hope to go from here.

It has long been thought that genetics might play a role in Parkinson’s, and this question has been the subject of much research. In the early 2000s, this field was extremely competitive and not very collaborative.

“The stakes were high, there was little reward for second place … and there was little mechanism for shared success,” the researchers wrote.

Beginning around 2005, however, technological advancements and initiatives such as the Human Genome Project started to facilitate genetic research with data on a scope and scale that had not been possible before. Critically, the more data available for these analyses, the more powerful they are — and as such, there was a strong need for data-sharing and collaboration.

“The IPDGC was born out of a realization that no single investigator could deliver on the promise of modern human genetics in isolation,” co-author Andrew Singleton, PhD, of the National Institutes of Health, said in a press release. “We realized that to truly leverage the incredible gains in genetic technologies in the PD space, at scale, would require a highly collaborative approach.”

IPDGC was the result of a 2009 meeting that included about 10 researchers in Paris. Since then, the group has grown to more than 100 researchers around the world. They hold annual meetings, and recently started new research initiatives in Africa and the Middle East — most of their research to date has focused on populations in Europe and the U.S.

“The coordinated analysis of genome-wide association (GWA) data was perhaps the first success for IPDGC and has continued to be a mainstay of our work,” Singleton said.

GWA involves looking for genetic variations that tend to be associated with a particular condition — in this case, Parkinson’s. The IPDGC has performed GWA studies using data its researchers have collected as well as data from industry collaborators such as 23andMe.

While the first of these efforts only included about 3,000 people, the most recent study had data for more than 50,000 people with Parkinson’s, as well as roughly 1.4 million people used as controls.

“As in other disorders, as sample size has grown, so has power and the number of loci detected,” the researchers wrote. “Currently, there are more than 90 known risk loci for [Parkinson’s].” (Loci are positions on a chromosome where a particular gene or genetic marker is located.)

Beyond the identification of risk loci, collaborations fostered by the IPDGC have also helped in understanding the biological processes underlying Parkinson’s disease. For example, such research revealed that Parkinson’s is associated with changes in the tissue of the brain itself, particularly in the cells of a region called the substantia nigra. This contrasts with Alzheimer’s disease, where similar dysregulation is typically seen in immune cells, not the brain cells themselves.

IPDGC’s research has also led to the discovery and validation of previously unknown pathways associated with the disease, and how mutations in these pathways can affect disease risk, such as how mutations in the VPS13C gene can be a cause of early-onset Parkinson’s disease.

This research has also contributed to the estimation that 16–36% of Parkinson’s risk has some kind of genetic basis.

Future work anticipated by the IPDGC includes more research to better understand the genomic architecture of Parkinson’s, particularly in groups of non-European descent, which have historically been understudied. This also involves more detailed studies looking for links between genetic variations and particular aspects of how Parkinson’s manifests from person to person.

The group also hopes to continue to facilitate efforts to build larger research cohorts and to share data and resources among researchers. For instance, one tool in development is the IPDGC sequencing browser, which allows users to look at sequence information for IPDGC data. Another, the IPDGC GWAS browser, is a community-driven site aimed at identifying previously unknown Parkinson’s genes.

“While we believe the work of the IPDGC has had a significant and lasting impact on our field over the last ten years, we are even more excited by the course we have charted for the next decade,” Singleton said.

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