Molecule May Halt Parkinson’s Progression, Study Using New Mouse Model Finds

anle138b molecule

A molecule called anle138b was able to reduce toxic alpha-synuclein aggregates, or clumps, in the brain — a key event linked to Parkinson’s — and reverse motor symptoms associated with the disease in a novel Parkinson’s mouse model.

The study, “Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson’s disease model,” was published in Acta Neuropathologica. The work was funded by the charity Parkinson’s UK.

Many neurodegenerative disorders involve aggregation of misfolded (harmful) proteins in the brain. Parkinson’s is characterized by a buildup of the protein alpha-synuclein in the brain, which forms clumps known as Lewy bodies that damage and kill nerve cells, or neurons.

Anle138b has been shown to reduce toxic protein accumulation and delay disease progression in models of multiple system atrophy, Alzheimer’s disease and Parkinson’s.

Investigators from the University of Cambridge now evaluated the effects of anle138b in a new mouse model of Parkinson’s disease.

Although this molecule had previously been shown to reduce the clumping of proteins in other Parkinson’s models, the team wanted to understand its potential to treat the condition during its natural progression. To that end, they created a new mouse model that mimics the way alpha-synuclein gradually accumulates in specific areas of the brain, impairing neuronal communication and resulting in motor alterations.

The animals were nine months old before treatment initiation — around 46 human years. At the start of the treatment, the mice already showed low levels of dopamine in their striatum, a brain region involved in voluntary movement control that is severely affected in Parkinson’s. This reduction was associated with the onset of motor symptoms, including changes in gait that resembled some of the early motor symptoms seen in individuals with the disease.

However, the animals’ substantia nigra, another brain region involved in motor function that is also affected by the disease, had not yet been significantly damaged. Mice striatal (meaning “of the striatum”) and nigral (meaning “of the substantia nigra“) dopamine-producing neurons also exhibited alpha-synuclein aggregation.

Starting at nine months of age, mice were treated with anle138b for three months. Treatment reduced alpha-synuclein clumps, restored dopamine levels in the brain, and prevented dopaminergic nerve cell death. This was accompanied by gait improvements, suggesting that anle138b can effectively reverse, or at least halt, Parkinson’s progression.

These results indicated that “there is a window of time when it is possible to prevent [dopaminergic] neuronal death, even when striatal [dopaminergic] release is already impaired,” the researchers said. This means that if anle138b is given early on — before advanced nerve cell death — it may reduce  alpha-synuclein aggregates, potentially halting Parkinson’s progression.

“Our study demonstrates that by affecting early alpha-synuclein aggregation with the molecule anle138b in a novel transgenic mouse model, one can rescue the dopaminergic dysfunction and motor features that are typical of Parkinson’s,” Maria Grazia Spillantini, professor in the department of clinical neurosciences at the University of Cambridge, and the study’s lead researcher, said in a press release.

“The evidence from this early stage study builds on our understanding of how alpha-synuclein is involved in Parkinson’s and provides a new model that could unlock future treatments,” added Beckie Port, research manager at Parkinson’s UK.

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Early Involvement of Caudate Brain Region Linked to Worse Prognosis in Parkinson’s Patients, Study Finds

caudate involvement

Almost half of people in the early stages of Parkinson’s disease already have signs of neurodegeneration in a brain region called the caudate, which was previously thought to affect mostly those at advanced disease stages, a study reports.

Early caudate involvement on both sides of the brain, as seen by DaTscan imaging of the brain, appeared to predict the risk for worse outcomes, including cognitive impairment, depression, and gait problems, over a four-year follow-up period.

These findings suggest that caudate involvement detected through DaTscan neuroimaging may serve as an early biomarker to identify patients at a greater risk of faster disease progression in the near future.

The study, “Clinical implications of early caudate dysfunction in Parkinson’s disease,” was published in the Journal of Neurology, Neurosurgery & Psychiatry.

Parkinson’s disease is believed to be caused by the impairment or death of dopamine-producing nerve cells (neurons) in a region of the brain called the substantia nigra, which controls the body’s balance and movement.

When the disease is established, or advanced, the degeneration of dopaminergic neurons and nerve fibers frequently extends to a brain region called the caudate nucleus. This region plays important roles in motor control as well as in various other non-motor tasks, such as learning and sleep.

In fact, the loss of dopaminergic function in this region is known to contribute to the hallmark symptoms of Parkinson’s including cognitive impairment, depression, sleep disorders, and gait problems.

Although less common, caudate dopaminergic dysfunction may also emerge in the early stages of the disease, in which case it could also contribute to the onset of non-motor symptoms. However, the frequency of this specific brain impairment in early Parkinson’s is unknown as are its clinical implications for patients.

To address this lack of knowledge, a team, led by researchers at the University of Milan in Italy and Newcastle University in England, investigated the prevalence of caudate dopaminergic dysfunction in people who were still in the very early stages of Parkinson’s.

By comparing the participants’ state at the beginning of the study and four years later, they also looked for associations between caudate involvement and an increased risk of disease progression.

They analyzed clinical data from 397 patients who had had a Parkinson’s diagnosis for two years or less, and were participating in the Parkinson’s Progression Markers Initiative (PPMI), an ongoing study attempting to identify biomarkers of disease progression. The team compared the collected clinical data from Parkinson’s patients with that of 177 healthy volunteers.

Caudate dysfunction was detected using 123I-FP-CIT single-photon emission computed tomography, commonly known as DaTscan. This is an imaging technique that depicts the levels of dopamine transporters in the brain that is often used to confirm a Parkinson’s diagnosis.

Based on DaTscan imaging data, the participants were divided into three groups: those who had no reduction of dopamine transporters, those who showed reduction in just one side of the brain, and those who had involvement of both sides of the brain.

Initial data showed that 51.6% of the patients had signs of normal caudate dopamine function, while 26% had caudate dopaminergic dysfunction on one side of the brain (unilateral), and 22.4% on both sides (bilateral).

Four years later, the patients who initially had bilateral caudate involvement were found to experience more frequent and worse cognitive impairment and depression, and more severe gait disability.

In general, after four years of follow-up, more patients showed a loss of dopaminergic nerve fibers in the caudate, compared with the study start, affecting 83.9% of patients (unilateral 22.5%, bilateral 61.4%).

“In this study, we have demonstrated a high frequency of early caudate dopaminergic dysfunction in patients with recently diagnosed [Parkinson’s disease],” the researchers wrote.

“Our study suggests that early bilateral caudate dopaminergic dysfunction is associated with an increased frequency of clinically significant depression and to worse depressive symptoms, regardless of age,” they added.

DaTscan parameters used to define the presence of early caudate dysfunction may be a “valid indicator of more rapid onset of such symptoms,” they said, which may help in “identifying patients at risk of clinical progression to cognitive impairment, depression, and gait problems in the near future.”

Assessment of caudate dopaminergic denervation may also assist clinicians in better predicting disease course at an early stage and identifying patients who may benefit the most from early, targeted disease-modifying therapies.

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#AANAM – Promising Blood Pressure Medicine Fails to Slow Parkinson’s Progression, Trial Results Show

Dynacirc study

In contrast to what was observed in mice, a hypertension medicine called Dynacirc (isradipine) failed to slow Parkinson’s disease progression in humans, according to Phase 3 clinical trial results.

However, “the study did not fail,” according to Tanya Simuni, MD, who presented “A Phase 3 study of isradipine as a disease modifying agent in patients with early Parkinson’s disease (STEADY-PD III): Final study results” during the 2019 American Academy of Neurology Annual Meeting in Philadelphia. Instead, the study’s negative results are important to understand how to fine-tune future approaches for effective treatments, Simuni said.

Belonging to a class of medications called calcium channel blockers, Dynacirc is used to treat high blood pressure (hypertension). The medicine relaxes blood vessels so the heart does not have to pump as hard, ultimately reducing blood pressure. Importantly, Dynacirc can penetrate the central nervous system and reach the brain, where it needs to exert its effects.

A preclinical study demonstrated that upon treatment with Dynacirc dopaminergic neurons — those that are lost as a consequence of Parkinson’s — had levels lower of oxidative stress than those of untreated mice, suggesting the medicine could have a protective role against oxidative stress damage.

Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them, resulting in cellular damage as a consequence of high levels of oxidant molecules. Importantly, the molecular phenomenon has been implicated in the degeneration of dopamine-producing neurons.

Researchers believe dynacirc can protect neurons by blocking calcium channels on the surface of dopaminergic nerve cells. Normally these cells are continuously flooded with calcium, fueling cells’ powerhouses (mitochondria), which ends up contributing to harmful oxidative stress and, consequently, nerve cell death.

STEADY‐PD III was a 36-month, Phase 3, placebo‐controlled study (NCT02168842) assessing the effectiveness of Dynacirc 10 mg daily (two daily 5 mg doses) in 336 participants with early Parkinson’s disease who were not receiving dopaminergic therapy.

Participants were assigned randomly to receive Dynacirc or placebo for three years. Subjects had to complete 12 in-person and four telephone visits, during which researchers evaluated patients’ motor, neuropsychiatric, and cognitive skills. Blood and urine samples also were collected.

There were a total of 68 serious adverse events among treatment groups, six of which were deemed possibly related to treatment.

Although considered safe and well-tolerated, the treatment failed to slow progression of Parkinson’s disability. Researchers believe this may have been due to several reasons, including late intervention or inappropriate dosing, as the dose was selected based on tolerability and may not have effectively blocked the desired calcium channels.

Another hypothesis is that this target might not be the leading cause of human Parkinson’s development, or that a single target may not be sufficient to treat or slow disease progression.

“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the three years of the study compared to the people who took a placebo,” Simuni said in a press release. “Of course, this is disappointing news for everyone with Parkinson’s disease and their families, as well as the research community.”

“However, negative results are important because they provide a clear answer, especially for the drug that is commercially available. We will all continue to work to find a treatment that can slow down or even cure this disease,” she added.

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Low Levels of Substance P in Saliva May Help Predict Swallowing Problems, Study Suggests

substance P dysphagia

Low levels in saliva of a molecule called substance P may help predict the development of swallowing problems in people with Parkinson’s disease, a small pilot study in Germany found.

Since this molecule works as communication signal between nerve cells in the body, this discovery suggests that impaired substance P activity may be an important contributing factor in the  development of this Parkinson’s complication.

The study, “Substance P Saliva Reduction Predicts Pharyngeal Dysphagia in Parkinson’s Disease,” was published in the journal Frontiers in Neurology.

The progression of Parkinson’s disease is associated with the loss of movement control, including control over muscles in the face, mouth, and throat. This can lead to speech problems and swallowing difficulties, which are known medically as dysphagia.

Such swallowing difficulties can severely affect a person’s ability to sustain healthy eating practices without needing additional support.

“Parkinson’s-related dysphagia affects the oral, pharyngeal and the esophageal phase of swallowing and occurs in all stages of the disease,” the researchers said.

However, this complication may remain undetected during early stages of Parkinson’s in many patients, which may prevent early diagnosis and timely care, they said.

Previous studies have shown that levels of the neurotransmitter substance P are reduced among elderly Parkinson’s patients who have aspiration pneumonia. This suggests that substance P may be involved in the underlying mechanism of the normal swallowing and cough reflex in the throat’s inner tissues, called the pharyngeal mucosa.

To learn more, German researchers explored the role of substance P in the progression of pharyngeal dysphagia in people with Parkinson’s.

The study enrolled 20 patients; half showed signs of swallowing difficulties. Researchers collected saliva samples from all patients and analyzed the levels of substance P.

Participants who did not have pharyngeal dysphagia were slightly younger, had Parkinson’s for fewer years, and also showed fewer signs of motor impairments caused by the disease as compared to patients with the complication. However, these differences were minor, and the groups were considered to be at similar disease stages.

The results showed that patients who did not have swallowing problems had 1.8-fold higher levels of substance P than those with dysphagia.

“Our findings could be another indication that, in early stages, loss of substance P containing neurons in the pharyngeal mucosa may lead to pharyngeal hyposensitivity and merely incipient pharyngeal dysphagia,” the researchers said.

Additional studies are warranted to further understand the role of substance P in Parkinson’s disease progression, the researchers said. They also recommended that further studies be done to evaluate substance P’s potential as a biomarker for early dysphagia.

Future research also should address the potential use of capsaicin — an active compound in chili peppers known to stimulate the release of substance P — as strategy to target the sensory system within the swallowing network of nerve cells, they added.

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Heel, Toe: Walking with Mindfulness


Slow Is the New Fast Jean Mellano

Mindfulness isn’t difficult, we just need to remember to do it.” — Sharon Salzberg

The ability to walk is something many of us, myself included, have always taken for granted. Now that I have Parkinson’s disease (PD), something that used to come as a matter of course to me is starting to deteriorate. PD has adversely affected my left side more than my right side. I find myself tripping more, since I tend to drag my left foot.

Walking now requires my conscious thought

Going for a walk is now more of a mindful task than an exercise for me. I find it much more therapeutic to focus on how I walk and be in the present moment than to think about the future and how my PD may progress. With each step I take, I concentrate on repeating to myself, “Heel, toe.”

My stride analysis

When there was snow on the ground, I decided to compare my walking steps when I did not focus on saying “heel, toe” with those from when I did. My footprints in the snow were very telling, so I took a photograph. On the left side of the photo are my steps when I was not thinking about my stepping patterns. You might notice that both feet show a bit of a drag in the snow. On the right side of the photo, as I moved forward, I really focused on flexing both of my feet and having my heel strike first. There are no signs of drag on either foot.

Am I putting too much thought into this?

Years of training to improve as a dancer and a cyclist have made analysis of my body movements come quite naturally to me. Whether it was improving my pedal stroke for more cycling power or perfecting my balance to do pirouette turns, I learned to be mindful and to be in touch with how my body was performing. Now I must use that skill to help myself be more attentive when I walk.

My neurologist says I tend to overthink things. I believe our greatest strengths can also be our greatest weaknesses. Sometimes, I do overthink, to the point of getting paralysis by analysis. However, I believe that mindful analysis of my PD symptoms (including my walking technique) is critical in helping me to create different ways of doing things that at one time (before PD) used to come as second nature to me.

Do not dwell in the past, do not dream of the future, concentrate the mind on the present moment.” — Unknown


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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Parkinson’s Gene Variant May Affect Gene Expression, Disease Progression, Study Suggests

A Parkinson’s disease genetic risk variant, called rs1109303, might have a direct impact on the expression of nearby genes INPP5K and CRK, influencing disease risk and progression, a study suggests.
The study, “Parkinson’s Disease Risk Variant rs1109303 Regulates the Expression of INPP5K and CRK in Human Brain,” was published in Neuroscience Bulletin.
Parkinson’s disease, the second most prevalent neurodegenerative disorder in the elderly, affects 1-2% of people over the age of 65 worldwide, and is characterized by the gradual loss of muscle control, sometimes accompanied by cognitive deficits.
Previous large-scale genome-wide association studies (GWAS) identified several genes that increase a person’s predisposition toward developing Parkinson’s, including SNCA, MAPT, NUCKS1, the HLA region, GAK, BST1, GBA, WNT3, RIT2, and LRRK2. GWAS are studies based on a method that scans the genome (all of the genes present in our DNA) looking for specific types of genetic alterations found more frequently in people with a particular disease.
Besides genetic risk factors, studies have reported that uric acid (urate) levels in blood serum may also contribute to increasing an individual’s susceptibility to Parkinson’s.
In 2015, a GWAS study found a direct association between urate levels and the rs1109303 risk variant, which is located within the noncoding sequence — regions that do not encode protein sequences — of the INPP5K gene.
At the time, scientists were convinced that the rs1109303 variant might influence disease progression by affecting the expression of nearby genes, namely MYO1C, PITPNA, SLC43A2, and CRK. Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein. However, at the time, they did not pursue this line of investigation further.
Now, researchers in China have gone back to the original hypothesis drawn in 2015 and set out to investigate whether the rs1109303 risk variant could regulate the expression of nearby genes INPP5K, MYO1C, PITPNA, SLC43A2 and CRK.
The team analyzed multiple large-scale expression quantitative trait loci (eQTL) data sets, including a total of 22 human brain and 34 non-brain tissue samples from healthy donors and patients with neurological disorders. Expression quantitative trait loci are specific locations within the genome that contain genes encoding for traits that can be measured in a quantitative way.
The first eQTL data set from the Brain eQTL Almanac (Braineac) included 10 eQTL data sets from 10 brain regions of 134 healthy individuals.
The second eQTL data set from the Genotype-Tissue Expression (GTEx) database included a total of 449 donors — healthy individuals (94%) and subjects with neurological diseases (6%) — with a total of 7,051 samples from 44 different tissues.
And the third eQTL data set included whole blood data from three different studies involving 5,311, 2,116 and 5,257 individuals.
Analysis of the Braineac data set showed that the rs1109303 variant was associated with an increase in the expression of the CRK gene in the occipital cortex — the visual processing center of the brain.
In the GTEx data set, the rs1109303 variant was linked to an increase in the expression of INPP5K in the anterior cingulate cortex — an area of the brain that plays a role in regulating blood pressure and

Source: Parkinson's News Today

Parkinson’s Subtypes Share Early Psychiatric Features, But Diverge as Disease Progresses, Study Suggests

motor subtypes

In the early stages, three motor subtypes of Parkinson’s disease share similar psychiatric and cognitive features, with the distinct psychiatric profiles associated with each type only appearing as the disease progresses, a study suggests.

The study, “Psychiatric profile of motor subtypes of de novo drug-naïve Parkinson’s disease patients,” was published in the journal Brain and Behavior.

Parkinson’s disease is a diverse neurodegenerative disorder with distinct motor and non-motor symptoms. It is already known that different motor subtypes of the disease evolve with different clinical courses and prognoses.

Parkinson’s can be divided into three main clinical subtypes according to the predominant motor features: tremor-dominant, where tremor is a predominant symptom of the disease; akinetic-rigid or postural instability gait difficulty, characterized by stiffness or inflexibility of the muscles; or mixed, with no prevailing motor features.

Patients diagnosed with akinetic-rigid usually show a faster disease progression and are at higher risk of developing disability and dementia. On the other hand, progression of the tremor-dominant form is slower and associated with less cognitive decline, visual hallucinations, and depression.

These differences are attributed to lower dopamine levels in the brains of akinetic-rigid patients than in those with the tremor-dominant subtype.

Italian researchers studied the psychiatric, cognitive, and motor profiles of these three Parkinson’s subtypes in early, untreated Parkinson’s patients. They used untreated patients to avoid bias of the medication effect.

They included 68 newly diagnosed Parkinson’s patients, of whom 39 were akinetic-rigid, seven were mixed, and were 22 tremor-dominant. The participants underwent a complete assessment of psychiatric symptoms, including depression, anxiety, and apathy; cognitive issues, such as memory, language, attention; and motor features.

No differences were observed among the three Parkinson’s subtypes in any of the psychiatric and cognitive variables assessed. Researchers hypothesize that psychiatric differences among the three motor subtypes are not present in the very early stages of the disease, suggesting that a possible differentiation emerges only over the progression of the disease and potentially with its interaction with dopaminergic replacement therapy.

“This idea is widely supported by the literature on PD patients with longer disease duration and under antiparkinsonian treatment showing greater cognitive deterioration and psychiatric symptoms in AR patients,” the authors wrote.

“The evolution of psychiatric features is not predictable based on early motor presentation and regular follow-ups are needed to investigate their different possible progression,” they concluded.

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Retinal Thinning Linked to Parkinson’s and Likely Disease Severity in Newly Diagnosed Patients, Study Finds

retinal thickness and Parkinson's

Thinning of the eye’s retina appears to be associated with Parkinson’s and, possibly, with disease severity, a study reports, suggesting that an eye scan might be used at some point to detect Parkinson’s in its earliest stages, before motor symptoms begin.

The study, “Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease,” was published in the journal Neurology.

Visual impairment is a common non-motor symptom of Parkinson’s, which is known to affect patients at the early stages of the disease.

Advances in imaging technology have allowed researchers to obtain high-resolution images of the retina — the layer of nerve cells at the back of the eyeball that sends impulses to the brain, forming a visual image.

Studies have shown that Parkinson’s patients have retinal thinning, which correlates with disease severity or duration.

For this reason, researchers in South Korea analyzed the relationship between thinning of the inner retinal layers and the loss of dopamine-producing neurons in newly diagnosed patients. Parkinson’s is characterized by the gradual loss of nerve cells in the brain that produce dopamine, a chemical substance that helps control movement.

They conducted extensive ophthalmologic (eye) examinations and obtained high-resolution images of each of the retina’s five layers in 49 Parkinson’s patients (average age 69) and 54 age-matched controls. The patients had, on average, been diagnosed with Parkinson’s on average two years earlier, but were not yet on medication.

Results showed patients had significantly more thinning of the retina compared to age-matched controls. This was particularly prominent in its two inner-most layers, known as the ganglion cell and the inner plexiform layer, with the inner-most layer showing  an average thickness of 35 micrometers (μm) in one section, compared to an average 37 μm in controls.

The thickness of these two retinal layers was linked to disease progression: the lesser the thickness, the greater the disease progression.

Twenty-eight patients also underwent dopamine transporter positron emission tomography (PET) imaging, which evaluates the density of dopamine-producing cells in the brain.

A positive association was found between retinal thinning and loss of dopamine-producing cells in the left substantia nigra — the part of the brain involved in Parkinson’s pathology.

“Retinal thinning is present in the early stages of PD, correlates with disease severity, and may be linked to nigral dopaminergic degeneration,” the researchers wrote.

“Our study is the first to show a link between the thinning of the retina and a known sign of the progression of the disease — the loss of brain cells that produce dopamine,” Jee-Young Lee, MD, PhD, with the Seoul National University Boramae Medical Center and a study author, said in a press release.

“These discoveries may mean that neurologists may eventually be able to use a simple eye scan to detect Parkinson’s disease in its earliest stages, before problems with movement begin,” Lee added.

However, larger studies are necessary to confirm these findings and understand why retinal thinning and the loss of dopamine-producing cells are linked, Lee suggested.

“If confirmed, retina scans may not only allow earlier treatment of Parkinson’s disease but more precise monitoring of treatments that could slow progression of the disease as well,” he said.

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Source: Parkinson's News Today

2 Markers of Parkinson’s Progression May Help Trials in Newly Diagnosed Patients, Study Says

Parkinson's cognitive decline

Clinical trials in patients with early stage Parkinson’s may benefit from assessing markers of disease progression — namely, changes in the Movement Disorder Society (MDS)-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and dopamine transporter imaging, according to five-year results in a major observational study.

The study, “Longitudinal Change of Clinical and Biological Measures in Early Parkinson’s Disease: Parkinson’s Progression Markers Initiative Cohort,” was published in the journal Movement Disorders.

A lack of reliable and objective measures of Parkinson’s progression is a major stumbling block for researchers trying to develop disease treatments.

The Parkinson’s Progression Markers Initiative (PPMI) is an ongoing observational study that opened in 2010 and is now running at sites in 11 countries and involves about 1,000 people. It aims to speed the development of Parkinson’s therapies by evaluating the efficacy of several markers of disease progression in a large cohort of newly diagnosed Parkinson’s patients and healthy controls.

In total, 423 Parkinson’s patients were recruited for this study, and 358 remained with it for the five years. All were untreated at the study’s start, but soon began treatment with dopaminergic therapies, such as levopoda or dopamine agonists, or other Parkinson’s medications (non-dopaminergic).

Participants were evaluated every six months for a set of different clinical parameters, including MDS-UPDRS, the most commonly used and preferred scale for measuring Parkinson’s disability. But current data is limited on the long-term rate of change for this scale in newly diagnosed patients.

In the study, MDS-UPDRS scores were assessed at two different stages — during off-time periods, typically more than six hours after the last dose of dopamine therapy, and on-time periods or about one hour after taking this treatment.

Patients using non-dopaminergic therapies were assessed during on-time periods only.

All underwent dopamine transporter (DAT) imaging at baseline (study’s start) and at years one, two, and four of the study. DAT can establish the presence of presynaptic dopamine deficiency, and is increasingly used in clinical trials to exclude people without evidence of such deficiency because they are unlikely to have the pathology that typically causes Parkinson’s.

Data showed significant differences in the rate of change in  MDS-UPDRS in those who began dopaminergic therapy compared to those who remained untreated throughout the first year.

“Dopaminergic therapy provides a robust symptomatic benefit in early Parkinson’s, and once dopaminergic therapy is initiated, the rate of change of motor disability flattens until participants reach more advanced stages of Parkinson’s disease dominated by levodopa-resistant symptoms,” the researchers wrote.

A fraction of those treated with non-dopaminergic therapies also showed a change in MDS- UPDRS, but the changes were closer to untreated patients.

“These data reflect the lower potency of these agents,” the researchers said.

People who had no need to begin dopaminergic therapies had milder disease at baseline.

During the study, the researchers saw a marked decrease in dopamine transporter binding, with higher levels evident in the study’s first year compared to years two and four.

Changes in MDS-UPDRS scores and dopamine transporter imaging data did not correlate directly, the team reported, suggesting these two measures are valid on their own as they measure different aspects of Parkinson’s disease that can occur at the same time.

“Our results provide a framework for designing studies that incorporate clinical and DAT imaging measures in de novo Parkinson’s disease participants,” the researchers wrote. “Such studies may signal a more accurate and efficient process toward the development of disease-modifying treatments for Parkinson’s disease.”


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Source: Parkinson's News Today

Vitamin B12 Supplements May Help Slow Parkinson’s Progression, Study Finds

Vitamin B12 supplement

Low levels of vitamin B12 in patients in the early stages of Parkinson’s disease are linked to faster motor and cognitive decline, suggesting that vitamin supplements may help slow the progression of these symptoms, a study has found.

The study, “Vitamin B12 and homocysteine levels predict different outcomes in early Parkinson’s disease,” was published in the journal Movement Disorders.

Several previous studies have shown that B12 deficiencies are common in Parkinson’s patients. Deficiency of this vitamin promotes development of neurological and motor symptoms associated with the disease, including depression, paranoia, muscular numbness, and weakness.

While most studies have addressed the association of B12 with more advanced Parkinson’s disease, little is known about its contribution in the early stages of the disease before treatment begins.

University of California San Francisco (UCSF) researchers analyzed B12 levels in 680 patients recently diagnosed with Parkinson’s who had not begun treatment. The participants were followed for two years, during which physical and cognitive evaluations were conducted, in addition to B12 assessments. After initial evaluations, the patients were given the option to take a controlled daily multivitamin supplement.

Patients were divided into three groups according to their B12 levels at the beginning of the study. Approximately 13% of the participants had borderline low levels of B12, and 5% had a B12 deficiency. No association was found between low vitamin levels and early motor or cognitive symptoms of Parkinson’s.

The team did find that over time, symptoms in patients with lower B12 levels developed more rapidly than those with higher levels: Patients with lower B12 levels had a significantly reduced ambulatory capacity than patients with higher levels.

“Our findings demonstrate that low B12 levels are associated with greater walking and balance problems, possibly due to the known effect of B12 deficiency on the central and peripheral nervous systems,” Chadwick Christine, MD, UCSF neurologist and lead author of the study, said in a university press release. “Alternatively, low B12 may have a direct effect on the progression of Parkinson’s disease, or it may be a marker of an unknown associated factor, perhaps correlating with another aspect of the disease or nutritional status.”

Subsequent analysis showed improved B12 levels in about 50% of participants, indicating they had chosen to take the multivitamin supplement. Disease progression in this group of patients was found to be much slower, based on the annualized average increase of disability on the Unified Parkinson’s Disease Rating Scale (UPDRS) score  — a measure of Parkinson’s disability. Patients with improved B12 levels had an increase to only 10.11 on the scale, showing less disability, compared with 14.38 in patients who maintained low B12 levels throughout the study.

The team also evaluated the blood levels of homocysteine, an amino acid that is usually elevated in people with low B12 levels. There was a significant association between high levels of homocysteine — thus lower B12 — and faster cognitive decline.

“Our results suggest that the measurement of B12 levels early in Parkinson’s may be beneficial,” Christine said. “If levels are at the low end of normal, supplementation to get the level into the middle or upper end of the normal range may slow development of symptoms.”

Further studies are warranted to shed light on how vitamin B12 might benefit Parkinson’s patients, and to fully address its therapeutic potential on disease progression.

The study was supported by funding from the Michael J. Fox Foundation, and gifts from the Ko and Tsu family and William and Mary Ann S. Margaretten.

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Source: Parkinson's News Today