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Coffee Decreases Parkinson’s Tremors in Men, Study Suggests

coffee, tremors and Parkinson's

Drinking coffee may reduce tremors in Parkinson’s disease patients, but only among men, a recent study suggests.

The study, “Sex-dependent Effects of Coffee Consumption on Newly Diagnosed Parkinson’s Disease,” was published recently in the journal BMC Neurology.

There is some evidence that drinking coffee reduces the risk of developing Parkinson’s disease, but the effect of coffee on motor symptoms in people who already have been diagnosed with Parkinson’s is less clear.

In this study, researchers recruited Parkinson’s patients (137 women, 147 men) and divided them into two groups: coffee drinkers (204 people), which included anyone who drinks coffee regularly, or used to, even if they don’t anymore, and; non-coffee drinkers (80 people) who never regularly drank coffee.

Compared to the non-coffee drinkers, coffee drinkers were disproportionately younger, male, better-educated, and were younger at symptom onset. Coffee drinkers had less motor impairment, as demonstrated by lower scores on the motor section of the Unified Parkinson Disease Rating Scale (UPDRS; 19.46 vs. 22.84); this included significantly lower scores for tremor (2.48 vs. 3.64), bradykinesia (slow movement; 2.48 vs. 10.83) and gait and posture (0.78 vs. 1.16).

Of note, resting tremor occurs when a person’s hands, arms, or legs shake even when they are at rest; action tremor occurs with the voluntary movement of a muscle.

When the researchers included other factors (age, sex, etc.) in their model, most of these differences were no longer statistically significant. However, tremor scores were still significantly lower among coffee drinkers. More specifically, coffee drinkers had significantly lower scores for tremors at rest (1.49 vs. 2.41), whereas scores for action tremors were not very much  different between the two groups once other variables were taken into account.

Furthermore, this association was dose-dependent. That is, the more coffee participants reported drinking, the lower their tremor scores tended to be.

Researchers then divided the patients by sex and performed a similar analysis. Interestingly, tremor scores were significantly lower among male coffee drinkers as compared to male non-coffee drinkers, but this association was not statistically significant for females. This suggests sex-dependent differences on the effects of coffee in Parkinson’s patients.

The researchers speculated that such differences may be attributable to hormones that are typically present at different levels between the sexes, most notably estrogen. But further research will be needed to determine whether this idea holds water.

“Coffee consumption and tremor severity are inversely related in male patients with de novo [Parkinson’s disease],” the researchers wrote. “Further investigations are needed to reveal the exact causal relationship between coffee consumption and tremor in [Parkinson’s disease] patients,” they added.

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Gene Therapy in Clinical Trial, AXO-Lenti-PD, Safe And Effective in Monkey Model of Parkinson’s, Study Says

gene therapy study

The experimental gene therapy AXO-Lenti-PD (OXB-102) was seen to be both safe and effective in a primate model of Parkinson’s disease, a study reported, supporting a clinical trial getting underway in patients.

The findings were published in the journal Molecular Therapy Methods & Clinical Development in the paper, “Gene Therapy for Parkinson’s Disease: Preclinical Evaluation of Optimally Configured TH:CH1 Fusion for Maximal Dopamine Synthesis.”

Parkinson’s disease is caused by a lack of the neurotransmitter dopamine in the brain as a consequence of the degeneration of dopamine-producing neurons. Oral dopamine replacement therapies (e.g., levodopa) can provide symptom relief, but their benefits tend to weaken — and unpleasant side effects multiply — when used over a long period.

The idea behind gene therapy for Parkinson’s is that, rather than swallowing a pill to get more dopamine, cells in the brain could be engineered to make more on their own. One such therapy, called ProSavin, demonstrated promising results in early clinical trials — but data also suggested that this gene therapy didn’t increase dopamine production enough for maximum benefit.

Like ProSavin, AXO-Lenti-PD gene therapy takes the form of a virus that has been modified to deliver a genetic payload that lets cells make more dopamine. But for AXO-Lenti-PD, the particular coding “instructions” have been optimized to get the most dopamine production possible. The therapy is administrated surgically directly into the brain.

AXO-Lenti-PD, developed by Oxford Biomedica and Axovant, is currently being evaluated in the SUNRISE-PD (NCT03720418) Phase 1/2 clinical trial that is enrolling patients at sites in England and France. To date, a single dose of  AXO-Lenti-PD is reported to be well-tolerated and to have improved motor function after six months in two people with advanced Parkinson’s disease.

In this preclinical study, researchers induced Parkinson’s-like symptoms in macaques using a compound called MPTP. The monkeys were then treated with either a high or low dose of AXO-Lenti-PD, or with ProSavin or a control vector. (Oxford Biomedica also developed ProSavin.)

Compared to animals in the control group, those given an active gene therapy showed significantly fewer parkinsonian symptoms at three and six months post-treatment. Although there were no statistically significant differences between the three treatment groups in terms of clinical scores, animals that received the high dose of AXO-Lenti-PD had higher motor scores than the ProSavin-treated animals at three and six months post-treatment.

Furthermore, assessment of the macaques’ brains suggested that those treated with either dose of AXO-Lenti-PD produced significantly higher levels of aromatic L-amino acid decarboxylase (AADC, an enzyme that helps in the production of dopamine) than those treated with ProSavin. The highest AADC expression was found in the high-dose AXO-Lenti-PD group, suggesting that this group had the most dopamine production (although this was not directly assessed).

AXO-Lenti-PD’s use also appeared to be safe. “Over the 26-week observation period, OXB-102 was demonstrated to be well tolerated and with no clinical signs or abnormal observations noted,” the team wrote.

Researchers did note that all animals given the investigational gene therapy developed antibodies against its viral vector, which may be a concern. Antibody development means that, if the vector were to be used again, it would likely be less effective because the body would fight it.

“In conclusion,” the researchers wrote, “the results achieved in these pre-clinical studies demonstrate the efficacy and safety of an enhanced dopaminergic lentiviral vector, OXB-102, and strongly support the clinical evaluation in patients with [Parkinson’s disease].”

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Senior Helpers Sending 6 Rock Steady Boxing Coaches from North Carolina to Group’s Conference

Rock Steady Boxing conference

Aware that non-contact boxing routines can improve the lives of Parkinson’s patients, Senior Helpers is sending six Rock Steady Boxing (RSB) coaches to the organization’s national conference.

Senior Helpers, a leading nationwide provider of at-home care, will sponsor the Wilmington, North Carolina, coaches in attending the second annual Rock Steady Boxing Coaches Conference to be held Sept. 4–6 in Phoenix.

At the conference, Rock Steady-certified coaches from around the world will learn the latest in techniques and practices. The non-profit Rock Steady Boxing uses a non-contact boxing-based fitness curriculum to help slow Parkinson’s progression and enable patients to better manage disease symptoms.

“As a care-based company, we understand firsthand how important it is to stay current with the skills and techniques that help our clients,” Mari Baxter, senior vice president of operations for Senior Helpers, said a press release.

“Rock Steady Boxing has been one of our most valued partners the past several years and the organization’s commitment to helping improve the lives of Parkinson’s patients is an exemplary example of humanitarianism,” Baxter added. “It’s our honor to help these coaches advance their skillsets and enhance their instruction.”

In general, research shows that exercise helps Parkinson’s patients maintain the abilities needed for a degree of independence in everyday life. In particular, exercises that stress gross motor movement, core strength, balance, and rhythm can positively affect patients’ range of motion, gait, posture, and flexibility.

The Senior Helpers-sponsored coaches are Mike Wilson, co-founder of Rock Steady Boxing of Wilmington and a former Jiu-Jitsu instructor; martial artist Val Wilson, who co-founded Rock Steady Boxing of Wilmington; Christy Gillenwater, a fitness studio owner who is certified as both a personal trainer and medical fitness specialist; multi-sport athlete Ryan Gillespie, a health and wellness veteran; Sheryl Johnson, a former police officer who was diagnosed with Parkinson’s in 2013; and Jim Cosper, a U.S. Navy veteran and Parkinson’s patient.

“Parkinson’s disease hits close to home for so many people, myself included,” Baxter said. “My husband Bill was recently diagnosed with Parkinson’s disease and has found Rock Steady to be an immense help in his overall wellbeing and day-to-day health. He was so resistant after his diagnosis, but now he’s their biggest convert.”

Founded in 2006 as the nation’s first boxing program of its kind, RSB is specifically designed to help patients at all stages of Parkinson’s. Visit this site to find a local class.

With more than 300 franchised businesses, Senior Helpers was founded in 2001 to help senior citizens with age-related illnesses and mobility challenges remain in their home.

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With BlueRock Acquisition, Bayer Plans to Open Trial of Cell Therapy for Parkinson’s

Bayer, BlueRock Therapeutics

Bayer has announced an agreement to acquire the cell therapy company BlueRock Therapeutics, and plans to open a clinical trial of a potential Parkinson’s stem cell-based treatment this year.

BlueRock, which will remain an independent entity under the plan, has a portfolio that focuses on engineered stem cell therapies to treat illnesses in the fields of neurology, cardiology and immunology.

Its lead program is in Parkinson’s, where preclinical work using BlueRock’s induced pluripotent stem cell (iPSC) technology has shown motor function improvement and higher dopamine production by stem cell-derived dopamine-producing neurons — those that are typically lost in distinct brain regions of Parkinson’s patients.

iPSC are derived from either skin or blood cells that have been reprogrammed back into a stem cell-like state, allowing for the development of a ready source of any type of human cell needed for therapeutic purposes.

According to Bayer, stem cell therapy could help reverse nerve cell degeneration by re-innervating the human brain and restoring motor function to people with Parkinson’s. Patients with multiple sclerosis, Alzheimer’s, Duchenne muscular dystrophy, congestive heart failure, and systemic lupus erythematosus may also benefit from BlueRock’s CELL+GENE platform, as the technology is called. It is designed to develop, manufacture, and deliver cell therapies with high purity, potency, and specificity.

Once the agreement in finalized, Bayer will own full rights to the iPSC technology, gene engineering, and cell differentiation capabilities of CELL+GENE.

“This acquisition marks a major milestone on our path towards a leading position in cell therapy,” Stefan Oelrich, a member of Bayer’s board of management and president of its Pharmaceuticals Division, said in a press release. “In line with our strategy to ramp up our investments in technologies with breakthrough innovation potential, we have decided to build our cell therapy pipeline based on BlueRock Therapeutics’ industry-leading iPSC platform.”

The agreement stems from a joint venture the Leaps by Bayer unit formed with Versant Ventures, setting up BlueRock in 2016. Leaps helps companies to become established and invests in early stage technologies with a potential to better treat, prevent, or cure major health concerns.

Bayer will acquire the remaining stake in the U.S.-based company for about $240 million in the coming months, with an additional $360 million to be given upon achievement of development milestones. The investment corresponds to a total BlueRock value of nearly $1 billion, according to the release.

Bayer’s support, said Emile Nuwaysir, PhD, BlueRock’s CEO, will aid its efforts to “pursue the discovery, development and commercialization of revolutionary new cell therapies” for patients with diseases “previously thought of as intractable.”

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Scientists Develop Simple, Affordable Way to Measure Tremors in Mice Using Smartphones

tremors, smartphone

Neuroscientists have developed a simple and inexpensive way to measure tremors, one of the main symptoms of Parkinson’s disease, in lab mice using a smartphone.

The new test showed comparable results to those generated with the expensive lab equipment currently used — opening a faster and more affordable way to test potential approved and investigational medicines, the scientists said.

“I thought it would be a pity if expensive equipment kept us from continuing our research to find treatments for tremor,” Eva Maria Meier Carlsen, the neuroscientist at the University of Copenhagen behind the new device, said in a press release. “That’s why I set out to find an affordable and valid way to measure it, and I came up with the idea of using a smartphone as a measuring device.”

Tremor is a common symptom of many neurological disorders, such as Parkinson’s disease, multiple sclerosis, and spinal cord injury. Although it greatly affects the quality of life of many patients, available treatments are few and non-specific. Tremor also is rarely measured in experimental mice because the required lab equipment is expensive, costing anywhere between $15,000 and $19,500.

Carlsen, a postdoctoral fellow at the university, came up with a simple solution: a smartphone. The method takes advantage of the accelerometer inside the phone — a device which detects tilt, motion, and acceleration, allowing the smartphone to tell up from down. The accelerometer is used in a phone’s compass function.

By fixing the smartphone to a cage suspended by rubber bands, Meier Carlsen and colleagues were able to measure the faint vibrations of the cage as the mouse trembled. In collaboration with Saniona, a company developing medications for the central nervous system, they determined that the accuracy of the new method was comparable with that of expensive commercially available equipment.

“It is a really good idea that Eva got, and our new study emphasizes its validity,” said Jean-François Perrier, associate professor at the Department of Neuroscience and head of the research project. “It is a good example of how we researchers sometimes have to challenge the conventions and invent new methods that are more accessible and can be used by more people.”

Meier Carlsen pointed out that the new method could be made even more affordable by omitting the smartphone entirely, and instead using a single-board computer — a small computing device fitted with an accelerometer.

The neuroscientists already are using this new method to test experimental medications for tremor in mice. They also plan to use it to test already approved therapies. If any of these proved effective, they could reach patients much sooner, the scientists said.

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Parkinson’s UK Awards Scientist £100,000 to ID Ways of Protecting Dopamine-producing Neurons

Parkinson's UK grant

A scientist at the University of Sheffield in England has been awarded a £100,000 grant by Parkinson’s UK to develop a treatment that might slow or stop the progression of Parkinson’s disease and protect brain cells.

The one-year grant, worth about $120,000, was given to Heather Mortiboys, a senior research fellow at the university’s Institute for Translational Neuroscience (SITraN), by Parkinson’s Virtual Biotech Programme, the British charity’s therapeutic development arm.

“All the clinical treatments for people living with Parkinson’s at the moment are based on easing these sometimes devastating symptoms,” Mortiboys said in a press release. “With this new funding award … we have the potential to go on to develop a drug treatment which will actively address the root cause of these symptoms to slow, or halt the progression of Parkinson’s for the first time.”

Mitochondria, power factories for cells that include dopamine-producing brain cells, don’t work as they should in people with Parkinson’s disease.  Resulting shortages in cellular energy cause neurons to fail and ultimately die, particularly dopamine neurons. Those nerve cells are responsible for movement and coordination, and rely on mitochondria to function.

In her previous work, Mortiboys developed a model of dopamine brain cells — using skin cells from patients — that allows researchers to test potential therapies. Her research team was able to grow high numbers of brain cells derived from these skin cells. They used them to identify compounds that support dopamine neurons and their mitochondrial function, and potentially lessen cell death.

With this award, Mortiboys and her team will try to pinpoint the molecules in these compounds that are of greatest benefit to mitochondria in producing the energy needed to support these brain cells. Working in collaboration with the National Institute of Health Research (NIHR) Sheffield Biomedical Research Centre, the scientists will then move the molecules into a drug discovery phase.

“There is an urgent need for treatments to protect the nerve cells that become damaged in patients with Parkinson’s disease, which will have a crucial impact in slowing the progression of the condition and improving the quality of life” said Pamela Shaw, director of SITraN and and the university’s new Neuroscience Institute.

Potential treatments identified through this process will be further developed through a partnership with the NIHR Biomedical Research Centre at the Royal Hallamshire Hospital, a Sheffield teaching hospital, Shaw said, adding “[w]e are hugely grateful to Parkinson’s UK for supporting this important translational research.”

“We are delighted to partner and work with Dr Heather Mortiboys and her team at the University of Sheffield. Through our Virtual Biotech initiative, we are committed to accelerating promising and breakthrough treatments for Parkinson’s,” said Richard Morphy, drug discovery manager at Parkinson’s UK.

“This is an exciting new approach that could rescue defective mitochondria inside neurons to prevent dysfunction and degeneration of dopamine-producing brain cells,” Morphy said.

Parkinson’s UK, which invests about $4.8 million a year in work that advances potential treatments, estimates that about 148,000 people in the U.K. have this neurodegenerative disease.

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Researchers Contemplate Salivary Alpha-Synuclein as Parkinson’s Biomarker

biomarker

Alpha-synuclein in saliva may be a potential biomarker for Parkinson’s disease, according to a recent review article, but more research is necessary to determine its reliability as a possible screening approach.

The study with that finding, “Salivary alpha‑synuclein as a biomarker for Parkinson’s disease: a systematic review,” was published in the Journal of Neural Transmission.

In Parkinson’s, a protein called alpha-synuclein clumps together, creating insoluble fibrils (small fibers) that accumulate inside nerve cells. These aggregates, known as Lewy bodies, are harmful to cells, eventually leading to cellular death, which then contributes to the onset of disease-related symptoms.

Unfortunately, alpha-synuclein aggregates can be confirmed only during an autopsy examination, so current diagnosis relies on Parkinson’s-related clinical symptoms instead of objective tissue changes.

That is why researchers are seeking reliable molecular biomarkers that can distinguish Parkinson’s from other conditions, monitor disease progression, or provide insight about a patient’s response to a given therapeutic intervention.

Lewy bodies have been found in the salivary glands of early-stage Parkinson’s patients. “Salivary alpha-synuclein is an easily accessible biomarker for PD [Parkinson’s disease] with promising results,” the researchers wrote.

The team decided to summarize the current knowledge of salivary alpha-synuclein as a potential biomarker for Parkinson’s. They searched the U.S. National Library of Medicine’s MEDLINE database from 1970 to April 2019 for several keywords related to Parkinson’s diseasem including “alpha synuclein,” “Lewy body pathology,” “saliva,” and “biomarker.”

Based on all their established criteria, researchers identified 476 studies, of which only eight had data on salivary alpha-synuclein, totaling 1,240 participants.

Of the eight studies, three reported total salivary alpha-synuclein levels (i.e., including all forms of the protein) were significantly lower in Parkinson’s patients, compared to healthy individuals, but the remaining five indicated no association between total alpha-synuclein concentration in saliva and the neurodegenerative disorder.

“In some studies, total salivary [alpha-synuclein] was associated with demographic and clinical features; however, no consistent pattern emerged. In one study, total [alpha-synuclein] levels were associated with poor cognitive performance in [Parkinson’s disease] patients,” the investigators noted.

Alpha-synuclein can be found in various molecular and structural forms. Half of the studies analyzed showed that people with Parkinson’s had higher levels of salivary oligomeric (aggregated) alpha-synuclein and a higher oligomeric alpha-synuclein/total alpha-synuclein ratio, than controls.

Additionally, one study indicated multiple genetic variants could alter total salivary alpha-synuclein concentrations in Parkinson’s. Nonetheless, in all studies there were important limitations to the scientific protocol and the corresponding results that may have influenced its conclusions. Some of those confounding factors included problems with sample collection, sample contamination, inadequate sample storage, or difficulties performing the tests.

“Utilization of saliva in biomarker discovery has several advantages over other biofluids. For instance, in comparison to CSF [cerebrospinal fluid, the liquid surrounding the brain and spinal cord] or serum/plasma, human saliva is readily accessible and is easier and less invasive to collect in adequate quantities,” the researchers explained.

Because of the minimal risk the approach imposes on the patient, salivary biomarkers may enable monitoring how the disease progresses and the effects of treatments.

Although studies suggest a decrease in total, and an increase in oligomeric,  salivary alpha-synuclein levels, results lack consistency. For now, salivary alpha-synuclein tests have yet to be adopted in clinical practice.

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Plant Antioxidant Seen to Aid Mitochondria and Ease Motor Problems in Early Parkinson’s Study

plants and antioxidants

Alpha-arbutin — an antioxidant found in plants such as blueberry bush — may restore mitochondrial function in nerve cells and ease the motor disabilities associated with Parkinson’s disease, according to a preclinical study from China.

Its results point to alpha-arbutin as a potential therapeutic compound for Parkinson’s and other disorders linked to problems in mitochondria, a cell’s energy source.

The study, “α-Arbutin Protects Against Parkinson’s Disease-Associated Mitochondrial Dysfunction In Vitro and In Vivo,” was published in the journal NeuroMolecular Medicine.

Parkinson’s disease is characterized by the degeneration and death of a specific group of nerve cells — called dopaminergic neurons —  in the substantia nigra, a region of the brain that regulates muscle movement and coordination. To work as intended, these nerve cells require large amounts of energy, which is provided by mitochondria.

Mitochondria are small organelles inside cells that, apart from being a cell’s “powerhouse,” are also the main producers of free radicals, or reactive oxygen species, which are associated with oxidative stress. Oxidative stress results from an imbalance between the production of free radicals and a cell’s ability to detoxify them, leading to cellular damage.

Increasing evidence suggests that both mitochondrial dysfunction and oxidative stress contribute to the degeneration of dopaminergic neurons seen in Parkinson’s disease. Compounds that can reduce mitochondrial dysfunction or oxidative stress may protect these neurons, and be potential therapies for Parkinson’s.

Alpha-arbutin, a natural compound extracted from plants of the heath family (Ericaceae) — which includes blueberry and bearberry bushes, and cranberry bogs — was shown to have antioxidative properties and to suppress the production of a key mediator of oxidative stress in Parkinson’s disease.

Researchers set out to evaluate the therapeutic potential of alpha-arbutin in two established preclinical disease models.

The first model involved nerve cells grown in the lab and treated with rotenone, a pesticide known to impair mitochondrial function, promote their production of free radicals, cause cellular death, and lead to parkinsonian features.

Giving alpha-arbutin to nerve cells before rotenone (pre-treatment) eased this pesticide’s toxic effects, suppressing free radical production and increasing the levels of antioxidative molecules. This worked to promote an oxidative balance, leading to fewer dead nerve cells.

Pre-treatment with alpha-arbutin also attenuated rotenone-induced mitochondrial damage to the cells and restored their ability to engage in autophagy, a vital cellular recycling system that removes or recycles unnecessary or dysfunctional components. Rotenone suppresses this natural process, damaging and killing cells.

These results suggested that alpha-arbutin’s neuroprotective effects were associated with a reduction in oxidative stress, and the maintenance of mitochondria function and autophagy processes.

Researchers then evaluated whether alpha-arbutin could ease Parkinson’s-associated symptoms and mitochondrial damage in fruit flies lacking the PRKN gene. Mutations in PRKN are known to trigger mitochondrial dysfunction, loss of dopaminergic neurons, and early-onset Parkinson’s disease.

Feeding these mutated flies alpha-arbutin significantly improved their climbing ability and wing posture, whose pre-treatment abnormalities are considered characteristic disease symptoms. The treatment also restored their mitochondrial structure and increased their energy production.

These findings, the researchers said, show for the first time that alpha-arbutin is able to not only significantly reduce rotenone-induced oxidative stress and mitochondrial dysfunction in nerve cells, but can also rescue motor problems and mitochondrial abnormalities in an animal model of Parkinson’s disease.

“Naturally derived-antioxidants might serve as a new class of therapeutic options for PD [Parkinson’s disease],” the researchers wrote.

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Low Vitamin D Levels Linked to Added Falls, More Sleep Problems, Depression, Study Shows

low Vitamin D

Low vitamin D levels are associated with a greater tendency for falls, sleep problems, anxiety, and depression in people with Parkinson’s disease, according to a recent study.

The findings, “Relationship between 25‐Hydroxyvitamin D, bone density, and Parkinson’s disease symptoms,” were published in the journal Acta Neurologica Scandinavia.

Vitamin D deficiency and low bone mass are frequently observed in people with Parkinson’s disease (PD). In fact, one particular study found that lack of this vitamin is more common in people with Parkinson’s (55% of patients) than other populations, such as people with Alzheimer’s disease (41% of patients).

But the relationship between vitamin D levels and Parkinson’s has remained controversial. Some studies suggest that taking vitamin D3 — a form of vitamin D used in supplements — can stabilize the disease, while others see no relation with the risk of Parkinson’s.

However, most studies have focused on limited aspects of the disease and did not include important outcomes — notably, non‐motor symptoms.

Vitamin D has a vital role in bone health, since it promotes calcium absorption and bone mineralization, which keeps bones strong and healthy. It also blocks the release of parathyroid hormone (PTH), an hormone that promotes bone tissue reabsorption and bone thinning.

Some studies support that lack of vitamin D results in a greater risk of falls and fractures in Parkinson’s patients, which can increase hospitalization and even fatal disability. Its levels also have been associated with cognition and mood, as well as stomach malfunction, in people with the disease.

While it is possible that deficits in this vitamin impact several symptoms of PD, the connection remains unclear.

To shed light on this relationship, researchers at the Second Affiliated Hospital of Soochow University and Soochow University, in China, set out to determine if vitamin D levels correlated with bone mineral density (BMD) and non‐motor symptoms in Parkinson’s patients.

The team measured blood levels of 25-hydroxyvitamin D, or 25(OH)D — a precursor of the active form of vitamin D and the most accurate indicator of vitamin D levels in the body — and performed extensive clinical evaluations in 182 Parkinson’s patients as well as 185 healthy people (controls).

Participants were recruited from the Second Affiliated Hospital of Soochow University from March 2014 to December 2017.

Bone mineral density — a measure of bone mass and health — was measured at the lumbar spine and the top of the femur (thigh bone) by bone densiometry, which measures bone loss.

The data showed that people with Parkinson’s had significantly lower vitamin D levels in the blood compared with healthy controls — an average of 49.75 versus 43.40 nanomol per liter of 25(OH)D.

In agreement, low levels of vitamin D (below 50 nmol/l) also were more common in Parkinson’s patients (68.68%) than controls (54.05%).

People with lower vitamin D levels were more likely to fall and experience sleep problems, including difficulty in falling asleep (insomnia). They also had significantly more depression and anxiety.

Mean bone densities in both the spine and femur were lower in PD patients, however no correlation was seen between the levels of BMD and vitamin D.

“Together, these results indicate that vitamin D deficiency may play a role in PD pathogenesis [disease manifestations], while vitamin D supplementation may be used to treat the non‐motor symptoms of PD,” the researchers  said.

“As various non-motor symptoms place a burden on individuals with Parkinson’s disease and their caregivers, vitamin D might be a potential add-on therapy for improving these neglected symptoms,” study’s senior author Chun Feng Liu, MD, PhD, said in a press release.

However, the researchers stressed that future studies with a larger sample size are necessary to clarify the role of vitamin D in Parkinson’s disease.

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Specific Dopamine-producing Neurons Crucial to Adaptive Movement, Early Study Finds

motor skills and Parkinson's

Dopaminergic neurons — nerve cells gradually lost to Parkinson’s progression — that contain an enzyme called aldehyde dehydrogenase 1A1 are essential for acquiring the motor skills needed for proper movement in given situations, a mouse study reports.

The research, “Distinct connectivity and functionality of aldehyde dehydrogenase 1A1-positive nigrostriatal dopaminergic neurons in motor learning,” was published in Cell Reports. The work was developed by the Intramural Research Program of the National Institute on Aging (IRP-NIA).

Parkinson’s disease severely affects dopaminergic neurons, those that produce dopamine, a neurotransmitter (cell-signaling molecule) that relays information between nerve cells and between the brain and the rest of the body.  These neurons are found in two specific brain regions involved in motor control: the striatum and the substantia nigra.

Nerve cells may or not contain aldehyde dehydrogenase 1A1 (ALDH1A1), an enzyme that is involved in cellular detoxification. Parkinson’s seems to mostly damage ALDH1A1-positive dopaminergic neurons, suggesting the enzyme may be a key player in this neurodegenerative disorder.

Both ALDH1A1-positive and ALDH1A1-negative dopaminergic nerve cells contribute to voluntary motor behavior. But the degree to which ALDH1A1-positive neurons are crucial to acquiring motor skills remains to be understood.

Using a mouse model of Parkinson’s, scientists targeted  dopaminergic neurons positive for ALDH1A1, and produced a detailed connectivity map of these specific neuronal networks in the mouse brain.

ALDH1A1-positive neurons were found to be in constant communication with other brain structures there. Importantly, researchers found that those dopamine-producing neurons of the striatum and substantia nigra that received the greatest percentage of molecular information (input) were located in the caudate-putamen nuclei, a brain region involved in movement control.

Researchers then selectively removed ALDH1A1-positive neurons to mimic the degeneration pattern observed in late-stage Parkinson’s disease. The animals’ ability to show new motor skills — new ways of voluntary movement, like foot position for maintaining balance while walking on a moving surface — was assessed using the rotarod test. In this test, mice must learn to balance while walking on a constantly rotating rod much like a treadmill.

Mice without ALDH1A1-positive neurons displayed a distinctly poorer ability to learn new motor skills, and slower walking speeds compared to control animals.

“Compared with a modest reduction in high-speed walking, the ALDH1A1+ nDAN-ablated mice showed a more severe impairment in rotarod motor skill leaning,” the researchers wrote. “Unlike control animals … [these] mice essentially failed to improve their performance during the course of rotarod tests.” (nDANs are nigrostriatal dopaminergic neurons.)

These animals were then treated with dopamine replacement therapy, either levodopa or a dopamine receptor agonist, one hour before a new motor skills assessment. Dopamine replacement therapy is standard treatment for the motor symptoms associated with Parkinson’s.

Levodopa (L-DOPA) treatment allowed the animals without ALDH1A1-positive neurons to travel longer distances, and to walk more frequently at higher speeds during a session. But it failed to improve their ability to acquire new motor skills during repeated tests. Treatment with a dopamine receptor agonist was also ineffective.

“When the ALDH1A1+ nDANs were ablated after the mice had reached maximal performance, the ablation no longer affected the test results, supporting an essential function of ALDH1A1+ nDANs in the acquisition of skilled movements. These findings are in line with the theory that nigrostriatal dopamine serves as the key feedback cue for reinforcement learning,” the researchers wrote.

These results provide “a comprehensive whole-brain connectivity map,” they concluded, and reveal a key role of ALDH1A1-positive neurons in newly learned motor skills, suggesting that motor learning processes require these neurons to receive a multitude of information from other nerve cells and to supply dopamine with “dynamic precision.”

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