Exposure to Second-Hand Smoke Linked to Lower Risk of Developing Parkinson’s, Study Suggests

second-hand smoke

Second-hand smoke may have a neuroprotective effect, as exposure to this type of indoor pollutant seems to be associated with a decreased risk of developing Parkinson’s disease, according to a recent study.

Conversely, exposure to certain air pollutants — like nitrogen dioxide and ozone — might contribute to a higher risk of developing the disease.

The study, “The impact of long-term exposure to ambient air pollution and second-hand smoke on the onset of Parkinson disease: a review and meta-analysis,” was published in Public Health.

Air pollution is composed of a variety of particulate air pollutants, volatile organic compounds, gaseous air pollutants, and airborne metals. Exposure to polluted air has been consistently associated with adverse effects in respiratory and cardiovascular diseases, but little is known about the effects of such exposure in neurodegenerative disorders such as Parkinson’s.

Although the exact causes behind Parkinson’s disease are not fully understood, it is thought to be induced by “a complicated interplay of environmental and genetic factors,” according to these researchers.

As such, “further investigation of the modifiable risk factors of [Parkinson’s disease] is of imperative significance and expected to have broad implication for the primordial prevention of this disease,” they said.

Second-hand smoke is a type of indoor air pollution. Evidence indicates that active smokers have a 50% lower chance of developing Parkinson’s in comparison with non-smokers. “However, whether this negative correlation is causal and persists among persons regularly exposed to SS [second-hand smoke] remains undetermined,” the researchers said.

To learn more, the scientists searched five medicine-related databases for any observational or epidemiological evidence on the relationship between long-term exposure to air pollution and second-hand smoke and Parkinson’s susceptibility.

The studied air pollutants included: particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5), such as combustion particles, organic compounds, and metals; particulate matter with less 10 μm in diameter (PM10), including dust, pollen, and mold; nitrogen dioxides (NO2); ozone (O3); and carbon monoxide.

The researchers combined the results of 21 studies, involving a total 222,051 Parkinson’s patients, and performed a statistical review known as a meta-analysis.

A marginally significant higher risk of developing Parkinson’s disease was observed in those exposed to PM2.5, NO2, and O3. Although carbon monoxide was found to be positively associated with Parkinson’s susceptibility, statistical significance was not attained.

“Second-hand smoke conferred reduced risk of Parkinson disease, regardless of exposure occasions [at home/at work/in children] and timing,” the researchers said. This suggests that second-hand smoke might have a neuroprotective effect in those who are susceptible to developing Parkinson’s at some point in their lives.

Some possible explanations exist as to why cigarette smoke may be associated with a lower risk of Parkinson’s. One theory is that some tobacco smoke compounds contain properties that inhibit monoamine oxidase (MAO), an enzyme that plays a key role in the activation of MPTP, a well-known Parkinson’s-inducing neurotoxin, and that is involved in the degradation process of dopamine released by nerve cells.

“Other hypotheses include the direct neuroprotective effect of nicotine by stimulating dopamine release, upregulating nicotinic receptors, and inhibiting alpha-synuclein fibrillation, thereby suppressing and relieving parkinsonian symptoms,” the researchers said.

Given the many harmful effects of air pollutants, public and environmental health strategies that reduce outdoor air pollution levels could help lower the burden of Parkinson’s disease.

Despite the potential neuroprotective effect of second-hand smoke, caution is advised when interpreting these results, as more large-scale studies are necessary to fully understand such an association.

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Brain Cells Will be Studied in Space to Better Understand Parkinson’s and MS

Space Station research

An ongoing study onboard the International Space Station (ISS) is investigating how microgravity affects the development of immune cells in the brain, with the goal of understanding the cellular processes behind the neurodegeneration seen in Parkinson’s disease and primary progressive multiple sclerosis (PPMS).

Scientists hope that the results of the study will provide new disease biomarkers and accelerate the search for new therapy options for patients.

Earlier this year, the same group — from the New York Stem Cell Foundation (NYSCF) Research Institute and Aspen Neuroscience — launched a preliminary experiment to test their systems and methods. Custom flight hardware systems, onboard cell culture technology, and post-flight analytical methods tested in that run all contribute to this next experiment.

In the preliminary experiment, the researchers loaded patient-derived induced pluripotent stem cells (iPSC) and cells from healthy donors into CubeLabs, shoebox-sized labs-in-a-box, developed by Space Tango. Automated systems fed and cultured the cells inside the CubeLabs. At the end of the experiment, the cells were frozen for analysis in earthbound labs.

Of note, iPSCs are derived from either skin or blood cells that have been reprogrammed back into a stem cell-like state, which allows for the development of an unlimited source of any type of human cell needed for therapeutic purposes.

The current experiment will be the first study of long-term cell culture in microgravity. Onboard the ISS, patient-derived and control iPSC will be grown into three-dimensional neural organoids — simplified versions of an organ. These organoids will include microglia, which are immune cells of the brain whose dysfunction is thought to drive neurodegenerative diseases such as Parkinson’s and PPMS.

“Microglia are constantly scanning the brain for danger, and it’s starting to look like they overreact in neurodegenerative illnesses, contributing to the death of neurons,” Valentina Fossati, PhD, one of the lead investigators from the NYSCF, said in a press release. “Physical forces affect how these cells behave, and microgravity is a unique circumstance in which to tease apart these healthy and diseased behaviors.”

Microglia make challenging research targets. They cannot be safely harvested from patients’ brains, and mouse models of Parkinson’s and PPMS do not mimic all the features of these diseases in humans. Fossati and her colleague, Andres Bratt-Leal, PhD, of Aspen Neuroscience, believe the ISS provides a better environment for building models of these diseases.

The group hopes that by understanding how microgravity — known to increase proliferation and delay differentiation of stem cells — affects the development and dysfunction of microglia, they will learn how these cells function while migrating throughout the brain and interacting with neurons. This, in turn, can teach us how these processes change during disease progression.

Because microgravity affects even healthy nervous tissue, the results of this experiment may prove useful for astronauts. NASA points out that “exposure to microgravity and radiation, as occurs in the International Space Station, causes significant mechanical unloading of mammalian tissues, resulting in rapid physiological alterations.” This can lead to a number of risks. Understanding the mechanisms by which this occurs will help to guard against them.

“There is significant potential to advance our understanding of MS and [Parkinson’s] as we initiate these long-term studies of patient cells in microgravity now that we have completed our preliminary tests,” Fossati said in another press release. “We look forward to leveraging the unique capabilities of spaceflight research to better understand the role of microglia in multiple sclerosis and Parkinson’s disease, as well as how dysfunction in these cells can be targeted therapeutically.”

The experiment is scheduled to launch into space on Dec. 4, on the 19th SpaceX Commercial Resupply Services mission. The National Stem Cell Foundation provided funding for the study.

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RightEye’s Vision System for Early Diagnosis Named ‘Breakthrough Device’ by FDA

RightEye system

RightEye’s Vision System, an advanced eye-tracking device that measures eye tremors to help diagnose Parkinson’s disease at early stages, has been designated a breakthrough device by the U.S. Food and Drug Administration.

This FDA designation is given select medical devices or products that aim to more effectively treat or diagnose ” life-threatening or irreversibly debilitating diseases.” It streamlines processes to speed these devices’ development, testing, and agency review for approval, possibly allowing them to reach the market more quickly.

Currently, a Parkinson’s diagnosis relies on the outcomes of several neurological tests, and delays are common before a correct decision is reached.

“When assessing Parkinson’s disease, 60% of patients are misdiagnosed at least once, with one third of patients misdiagnosed twice. That is a terrifying and unacceptable statistic in the age of modern medicine,” George Gitchel, PhD, director of clinical research at the Southeast Parkinson’s Disease Research, Education, and Clinical Center (PADRECC), at the Richmond Veterans Affairs Medical Center, said in a press release.

“In my experience Parkinson’s patients often struggle for years, going from doctor to doctor trying to get a correct diagnosis,” Gitchel added.

Previous research has found tremors that prevent the eyes from fixing with stability are “pervasive” in people with Parkinson’s, and researchers have suggested that eye tremor be considered in diagnosing the disease.

The RightEye Vision System uses advanced eye-tracking technology to measure eye tremors, which usually develop in patients before other symptoms arise. This means that the device may help to detect Parkinson’s at early stages.

The size of a laptop, the system provides objective and accurate visual screening, generating reports that reflect hundreds of collected metrics.

“By providing quantitative, objective data to assist clinicians, I truly believe that RightEye will play a key role addressing this issue, while its FDA Breakthrough Designation will accelerate availability,” Gitchel said.  

The system received FDA clearance  for recording, viewing, and analyzing eye movements to help identify patients with troubled visual tracking in October 2018.

“With this FDA Breakthrough Device Designation, RightEye has an opportunity to address a critical unmet need in the fight against Parkinson’s disease,” said Adam Gross, co-founder and CEO at RightEye.

“The annual cost of Parkinson’s disease in America is estimated at approximately $52 billion. Earlier assessment, intervention, and more accurate diagnoses is anticipated to reduce these costs, while also improving patient outcomes and quality of life,” he added.

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New Collaboration Will Focus on Developing Parkinson’s Screening Software

hand writing software

Startup company Jesse Medical and researchers from the Royal Melbourne Institute of Technology (RMIT) have agreed to collaborate on the further development and commercialization of new software to enable early detection and improved monitoring of Parkinson’s disease.

The screening technology analyzes the results of seven specific drawing and writing tasks, including simple writing and drawing a spiral by joining dots, performed on an interactive tablet, allowing the identification of a patient-specific pattern of motor response.

Dexterity information collected through this software provides clinicians with real-time data on fine motor skills that can be used to differentiate between people who do not have Parkinson’s and those who may have the disease but still do not show its most common and visible motor symptoms.

“It’s long been known that Parkinson’s disease affects muscle control and habitual activities, so it affects how patients write and draw. Our technology translates that insight into a reliable assessment tool,” Dinesh Kumar, PhD,  a professor at RMIT and lead investigator of the team that developed the software, said in a news story from the institute.

Using only a pen, paper, and a drawing tablet, the software can evaluate speed and applied pen-pressure while a person performs specific writing and drawing tasks.

Results from a study that evaluated an initial version of the software demonstrated that the new tool had the potential to distinguish not only Parkinson’s patients from controls, but also patients with differing disease severity with an accuracy of 93%. The assessment tool has since been refined and can now also be used to monitor response to treatment.

“As our population ages, the number of people living with Parkinson’s is expected to increase dramatically, so knowing more precisely how the disease is progressing and understanding the effect of different treatments will be crucial in helping them manage their condition,” Kumar said. “Our technology is completely objective and it’s highly sensitive for both improvements and deterioration in dexterity.”

RMIT’s biomedical engineering team has granted Jesse Medical exclusive rights to conduct clinical trials and commercialize this innovative technology with the newly established agreement.

The startup company anticipates the launch of clinical studies to evaluate the potential of this diagnostic and monitoring tool in Australia and China in mid-2020. These trials are expected to support the anticipated approval of the software for commercialization by 2022.

“The agreement with Jesse Medical is an exciting step in bringing this much-needed technology into the hands of clinicians, to benefit the many people around the world affected by this condition,” Kumar said.

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No Link Between Drinking Alcohol and Increased Parkinson’s Risk in Women, Large UK Study Finds

alcohol, parkinson's risk

Drinking alcohol does not increase the risk of developing Parkinson’s disease in women in the United Kingdom, nor are there increased risks linked to the consumption of different types of alcohol, a large study has concluded

The study, “Alcohol intake and Parkinson’s disease risk in the million women study,” was published in the journal Movement Disorders.

Several studies have investigated the link between alcohol intake and the risk of Parkinson’s disease, albeit with contradictory results: While some reports suggest people who drink alcohol have a lower risk of developing Parkinson’s disease, other studies show no effect. 

Some studies have suggested that different types of alcohol (beer, wine, and liquor) can influence Parkinson’s risk differently, with low beer consumption linked to a lower Parkinson’s risk and liquor associated with a higher Parkinson’s risk. 

However, most of these studies have been retrospective — based on information collected about the past — which rely on people accurately remembering details about their lives, and many studies did not properly control for other influential lifestyle factors such as diet, exercise, and smoking (confounding factors), which can affect the conclusions. 

Moreover, many of these associations between alcohol and Parkinson’s were found in men but not women. 

Therefore, a team of researchers based at the University of Oxford in the United Kingdom conducted a prospective study — following individuals over time — of a large group of women in the U.K. to examine the association between Parkinson’s and alcohol intake. 

Participants were recruited from The Million Women Study — a U.K. initiative that collected information on the lifestyle and medical histories of more than 1.3 million women, ages 50 to 64, to investigate how reproductive and lifestyle factors affect women’s long-term health. 

At the beginning of the study, a total of 1,309,267 women without Parkinson’s completed a questionnaire on weekly alcohol consumption. They were asked to identify different alcohol types they consumed that each contained approximately 10 grams of pure alcohol (glass of wine, half-pint of beer/cider, or a shot of liquor) and reported a number of drinks per week ranging from no alcohol to 21 or more drinks. 

After 14 years, 44,524 participants completed an additional 24-hour diet recall questionnaire to measure their alcohol intake. 

Women who went on to develop Parkinson’s were identified through hospital or death records. After an average follow-up time of 17.6 years, a total of 11,009 women developed the disease. 

Data analysis found that, compared with drinkers, non-drinkers with an alcohol intake between zero and one drink per week had an increased risk of developing Parkinson’s. However, because some women in the early stages of Parkinson’s can change their drinking habits, the team excluded data from the first 10 years and found the risk for non-drinkers was lower.  

The higher Parkinson’s risk in non-drinkers may reflect that in the early stages of the disease, parts of the brain associated with alcohol drinking behavior may be damaged, making a person that goes on to develop Parkinson’s less likely to drink. 

For women who consumed more than 14 drinks per week, the risk of developing Parkinson’s was the same as women who drank one to two drinks per week, in both the first 10 years and after more than 10 years of follow-up. 

No increased risks were found between women who drank only one type of alcohol and those who drank more than one type. 

The research team also found no association between alcohol consumption and Parkinson’s in those who never smoked cigarettes, and these results remained whether women had cardiovascular disease, drank coffee and tea, or had a family history of Parkinson’s.

“In this analysis of a large, prospective cohort of women in the UK, we found little evidence for an association between usual alcohol intake and [Parkinson’s] risk,” the authors reported. “Nor was there any evidence of an association between intake of specific types of beverages and [Parkinson’s] risk.

“The results suggest that alcohol intake does not materially influence the risk of [Parkinson’s] in UK women,” they concluded. 

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Brain MRIs Can Be Used to Detect Early Signs of Parkinson’s Cognitive Impairment, Study Suggests

brain MRI

Brain magnetic resonance imaging (MRI) scans could be used to detect early and subtle markers of cognitive impairment in people with Parkinson’s, which may help predict patients’ prognoses and disease progression, a recent study suggests.

Such early detection also allows people with the neurodegenerative disease to start appropriate care strategies earlier, the researchers say.

The results of the study, “Texture features of magnetic resonance images: A marker of slight cognitive deficits in Parkinson’s disease,” were published in the journal Movement Disorders.

Cognitive impairment is a common non-motor symptom of Parkinson’s disease and a cause of significant disability for patients and a burden for caregivers. The extent and progression of cognitive deficits vary, with about 20.3% to 60.5% of individuals experiencing mild cognitive impairments (MCI). In more severe cases, such impairment can result in dementia.
Those at-risk can benefit from early detection of cognitive alterations, which allows them to initiate appropriate care strategies such as cognitive stimulation therapy. Such therapy can result in a marked improvement in cognition and quality of life, according to researchers. However, standard neuropsychological assessments are time-consuming and not easy to do in routine clinical practice. Moreover, such evaluations can be influenced by medication, pain, anxiety, and other factors.
Therefore, additional markers of cognitive deficits are needed for Parkinson’s patients, the researchers say. One potential option is the use of magnetic resonance imaging (MRI), an imaging exam that uses a powerful magnetic field, radio waves, and a computer to produce detailed pictures of the body’s internal structures.
“Texture features” — a well-known method of MRI image processing used for medical purposes — could offer insights on subtle brain changes.  These features could be used to detect the damage to brain cells, long before any symptoms of cognitive impairment develop.
Recognizing the potential of this method, a team of French researchers now tested whether such signals could be used as early markers of Parkinson’s cognitive impairments — “potentially even before the atrophy [loss of brain volume, a usual sign of cognitive decline] becomes manifest,” they said.

The team investigated if MRI texture analysis is sensitive enough to be an early marker of cognitive alterations, specifically of cognitive slowing, in Parkinson’s patients.

They analyzed brain MRI scans of 102 people with Parkinson’s from centers in Lille, France, and Maastricht, the Netherlands, who were involved in a previous study.

Based on tests of attention, memory, executive function, language, and visuospatial functions, three groups of patients were considered for the study. These groups were cognitively intact patients (PDCN); cognitively intact patients with slight cognitive slowing (PDCN-S); and patients with mild cognitive deficits, particularly in executive functioning (PD-EXE).

A group of 17 age‐matched healthy people (controls) was included for comparison. All participants were examined on a 3T whole-body scanner and T1‐weighted images were acquired.

Six regions of the brain previously reported to suffer from atrophy (volume loss) in Parkinson’s patients with cognitive impairments were specifically chosen by the researchers for analysis. These regions were the thalamus, the hippocampus, the puramen, the pallidum, the caudate nucleus, and the amygdala.

The researchers found that values for two texture features — skewness and entropy — could distinguish individuals who had normal cognition from those with slight cognitive slowing, and from those with mild impairments. Skewness is a parameter that quantifies the asymmetry of the intensity of MRI signals. Entropy represents the degree of uncertainty of the texture intensity.

These texture features were at three specific regions in the brain: the hippocampus, the thalamus, and the amygdala.

The values for these features gradually decreased in those patients with worse cognitive function, suggesting it is possible to detect early cognition deficits in people with Parkinson’s using MRIs. The researchers noted that the best performances regarding sensitivity and specificity were obtained by measuring skewness in the hippocampus. In fact, skewness in the hippocampus was a significant marker of slight cognitive slowing.
“Our results suggest that hippocampal neurons could be affected very early in PD patients, even before atrophy can be detected with commonly used methods, and this could cause a general slowing of information processing,” the researchers said.
“These results support the assumption that signal alterations associated with Parkinson’s disease–related cognitive decline can be captured very early by texture analysis,” they added.
The researchers believe that brain MRI imaging could be combined with other methods, such as cognitive assessments and electroencephalograms. That would allow scientists to build a combined model “not only for the profiling but also for the prognosis and the prediction of evolution” of cognitive impairment, they said.

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Iron Accumulation in Brain Detected With High-Resolution MRI Technique, Animal Study Shows

iron accumulation

An experimental model of Parkinson’s in non-human primates leads to the accumulation of iron — known to contribute to the underlying causes of the disease — in a brain area linked to motor control. This metal accumulation can be detected using a neuroimaging technique called susceptibility-weighted imaging, according to recent research.

The study, titled “The role of iron in Parkinson’s disease monkeys assessed by susceptibility weighted imaging and inductively coupled plasma mass spectrometry,” was published in Life Sciences.

Higher-than-usual iron levels have been found in a brain region — called the substantia nigra — in Parkinson’s patients. This brain area, which plays a key role in motor control, is particularly affected during the course of the neurodegenerative disease.

In non-human primates, scientists have observed that this iron accumulation is accompanied by the loss of neurons that produce the neurotransmitter dopamine. That chemical messenger is in short supply in Parkinson’s. Such high levels of iron also are thought to be correlated with an increased severity in motor deficits.

Various imaging techniques have been used to study Parkinson’s disease in distinct animal models and have been found to produce consistent results. However, such methods are rarely validated.

Now, using cynomolgus monkeys, or crab-eating macaques, researchers investigated the role of metal accumulation in the striatum and midbrain (both motor control areas) in Parkinson’s. The researchers evaluated the use of susceptibility-weighted imaging (SWI) to measure iron deposits in the brains of Parkinson’s monkeys.

SWI is a high-resolution magnetic resonance imaging (MRI) technique that is sensitive to the magnetic properties of blood, iron, and calcifications, or calcium build-up in the body. These substances disturb magnetic fields, producing a not-so-clear image in a standard MRI scenario. SWI provides a unique contrast, generating 3D high-spatial-resolution images.

The animals received a left-side carotid artery injection of MPTP, a neurotoxin that induces the death of dopamine-producing neurons and mimics Parkinson’s symptoms. The carotid artery is one of the arteries that supplies the brain with blood.

An SWI-MRI was performed before and after the monkeys had received the MPTP injections.

Around 4-to-6 days after the injection, the monkeys exhibited limb muscle stiffness and limb postural tremor, and lost the ability to move their muscles freely (called akinesia). Importantly, these effects were only observed on the body side opposite, or contralateral, to the injection’s site.

The MRI results indicated there were higher-than-usual iron deposits in the MPTP-lesion side of the substantia nigra compared with the opposite side in the same animal. Similar results were found when these animals were compared with the control group of monkeys, which had been injected with a saline solution. Despite this indication, statistical significance was not attained.

Nevertheless, “MPTP did not affect the iron levels in other brain regions of monkeys,” the researchers said.

Post-mortem analysis of brain samples revealed that MPTP treatment provoked the loss of dopamine-producing neurons in the substantia nigra. The scientists reported that approximately 67.4% of dopaminergic nerve cells were lost in the substantia nigra on the injection side, while 30.0% were lost in the contralateral (opposite) side.

Neuronal loss in the substantia nigra on the injection’s side was correlated with worse behavioral performance and with motor impairment.

Biochemical analysis showed that MPTP increased iron levels in the injection’s side of the animals’ midbrain, but not in the striatum. However, calcium and manganese levels, which have been previously linked to Parkinson’s molecular mechanism, were unaffected by MPTP treatment.

“Taken together, the results confirm the involvement of [substantia nigra] iron accumulations in the MPTP-treated monkey models for [Parkinson’s disease], and indirectly verify the usability of SWI for the measurement of iron deposition in the cerebral nuclei of [Parkinson’s disease],” the researchers concluded.

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High Exposure to Antibiotics May Increase Risk of Parkinson’s, Study Suggests

antibiotics, Parkinson's risk

High exposure to oral broad-spectrum antibiotics and those that kill anaerobic bacteria and fungi is associated with a high risk of Parkinson’s disease within the next decade or more, a study finds.

The findings were reported in the study “Antibiotic Exposure and Risk of Parkinson’s Disease in Finland: A Nationwide Case-Control Study,” which was published in Movement Disorders.

Excessive exposure to antibiotics may change gut bacteria composition, which in turn is associated with an increased risk of several psychiatric disorders, Crohn’s disease, and colorectal cancer. Now scientists are also starting to investigate the possible link between antibiotic use and Parkinson’s.

“The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson motor symptoms such as slowness, muscle stiffness and shaking of the extremities,” Filip Scheperjans, MD, PhD, principal investigator of the study and neurologist at Helsinki University Hospital, said in a press release.

“It was known that the bacterial composition of the intestine in Parkinson’s patients is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” he said.

To further explore the possible association between high exposure to antibiotics and the onset of Parkinson’s, investigators from Helsinki University Hospital in Finland carried out a nationwide case-control study to compare antibiotic exposure in a large group of people with and without Parkinson’s.

The study included data from 13,976 people who had been diagnosed with Parkinson’s in Finland between 1998 and 2014, and 40,697 people who were the same age and sex, and from the same place of residence, but who did not have the disorder (controls). Information from patients and controls was obtained from national registries.

Antibiotic exposure was estimated based on data about purchases of oral antibiotics and was analyzed in three different time-points: one to five years, five to 10 years, and 10 to 15 years before the onset of Parkinson’s. In their analyses, investigators also looked at antibiotic exposure after grouping medications in different categories (e.g. by chemical structure, antimicrobial spectrum, and mechanism of action).

“During the course of follow-up, 84.9% of [Parkinson’s disease] patients and 83.6% of controls had purchased at least 1 antibacterial course. Penicillins were purchased most frequently, constituting 22.8% of all purchases,” the researchers wrote.

On average, people with Parkinson’s purchased more antibiotic courses than controls (6.32 versus 6.25), but the controls were hospitalized more often due to bacterial infections (0.19 versus 0.16).

The strongest connection to Parkinson’s was found for exposure to oral macrolides and lincosamides, two different classes of antibiotics that target different types of bacteria and work by preventing bacteria from producing the proteins they need to survive.

Further analyses showed that exposure to broad-spectrum antibiotics such as tetracyclines, and those that specifically target anaerobic bacteria, were associated with an increased risk of Parkinson’s disease within 10 to 15 years.

In addition, other types of antibiotics, such as sulfonamides and trimethoprim, and antifungal medications, were found to be associated with an increased risk of the disease within one to five years.

“Although no conclusions regarding causality can be made, it is plausible that oral antibiotic exposure is one factor that makes the gastrointestinal tract more susceptible to [Parkinson’s] pathology,” increasing the risk of getting the disease, the researchers said.

“Our findings demand confirmation in different cohorts. However, if confirmed in future studies, a connection between commonly prescribed oral antibiotics and neurodegeneration could have major implications for prescribing practices and public health,” they added.

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New Large-Scale Data Portal Will Promote Parkinson’s Treatment Development

data portal

The Accelerating Medicines Partnership (AMP) for Parkinson’s (PD) has opened a data portal with de-identified information from 4,298 Parkinson’s patients and healthy control subjects for use by scientists seeking new treatments for the progressive neurodegenerative disease.

With unprecedented access to a data pool of this scale, investigators now can examine intricate data sets and conduct full-scale genomic analyses.

“AMP PD is a true example of the whole being greater than the sum of its parts,” said Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke (NINDS), in a press release. “The combination of many data sets could allow researchers greater power to analyze potential biomarkers for Parkinson’s disease. This effort follows other AMP programs which have the shared goal of changing the way we go about the business of studying disease.”

Launched in 2014, the AMP is a public-private partnership between the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), multiple biopharmaceutical and life sciences companies, and non-profit organizations. Its goal is to transform the current model for developing new diagnostics and therapies by collaboratively identifying and validating promising biological treatment targets. The overarching mission is to develop new diagnostics and therapies relatively faster and at less cost.

Initial projects included Alzheimer’s disease, Type 2 diabetes, and rheumatoid arthritis, and lupus.

Last January, the AMP project on PD was launched. Managed by the Foundation of the National Institutes of Health (FNIH), the project includes the NIH, FDA, the Michael J. Fox Foundation (MJFF) for Parkinson’s Research, Celgene, Verily Life Sciences, Pfizer, Sanofi and GSK.

This project’s aim is to speed therapy development by providing the expertise and support necessary to learn which biomarkers demonstrate the most promise for predicting PD and disease progression. Biomarkers are molecular disease indicators.

“One important part of this platform is that, in addition to providing a place for storing complex data, we are also providing the tools to analyze that data within the platform itself,” said Debra Babcock, MD, PhD, NINDS program director and co-chair of the AMP PD steering committee. “In this way, we are bringing scientists to the data, which will increase opportunities for collaboration.”

Data in the officially named AMP PD Knowledge Portal was collected through the MJFF, NINDS and several other programs, studies and institutions. It includes information from samples of DNA, RNA, plasma, and cerebrospinal fluid, which is the liquid that surrounds the brain and spinal cord. The portal also offers a platform that can assimilate additional types and sources of data. For example, there is an upcoming study involving proteomics, the large-scale study of proteins.

With the longitudinal data in the portal, scientists can study patients’ information throughout the disease course. And, the data have been harmonized, allowing for comparison of information from different programs, and providing best practices for how to incorporate into the platform data from the PD community.

“The AMP model has provided a unique platform for bringing together diverse patient cohorts, advances in technology and scientific expertise to study Parkinson’s disease on a scale that has not been attempted before,” said David Wholley, senior vice president, research partnerships, FNIH. “With the AMP PD Knowledge Portal, we are helping the scientific community worldwide to fast-track discoveries that we hope will ultimately help Parkinson’s disease patients and their families.”

Scientists may visit this site to apply for access to the knowledge portal and interact with the data set.

Globally, roughly 7 to 10 million individuals have Parkinson’s, the second most common neurodegenerative disorder after Alzheimer’s disease.

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Sunovion Re-Submits Approval Request for APL-130277 to FDA for Treating Parkinson’s Off Periods

APL-130277 fda resubmission

Sunovion Pharmaceuticals has re-submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA), once again seeking the approval of its below-the-tongue formulation of apomorphine — called APL-130277 — for Parkinson’s off periods.

The re-submission is a follow-up to the FDA’s “complete response letter” from earlier this year, in which the agency requested additional information — but no new clinical trials — before deciding whether to approve APL-130277.

The new submission includes additional analysis of clinical data, and information about the intended packaging of APL-130277, according to Sunovion.

Off periods in Parkinson’s are characterized by the reappearance or worsening of symptoms such as tremors and dyskinesia, or involuntary movements. These effects are due to a gradual decline in the effectiveness of levodopa, which is the first-line therapy for the neurodegenerative disease. About half of all patients on levodopa experience off episodes, which, although frequent in the morning after awakening, may occur multiple times throughout the day. These episodes become more frequent and severe as the disease progresses.

In the U.S., people with Parkinson’s currently have only Apokyn (apomorphine hydrochloride), developed by US WorldMeds, as an approved medicine for off periods. A form of apomorphine, the medicine is able to quickly penetrate the brain, where it stimulates dopamine receptors to provide short-term relief. However, Apokyn’s subcutaneous, or under-the-skin delivery may cause pain and injection-site reactions.

APL-130277 is a sublingual or under-the-tongue formulation of apomorphine, which may be easier for patients to take. It is intended to provide on-demand and fast-acting lessening of all types of off episodes — meaning those that are unpredictable, those that occur at the end-of-dose, or those occurring after awakening in the morning.

The therapy was designed to be administered up to five times a day, with a minimum of two hours from the prior dose.

This new formulation of the medication contains a two-layer film — one with apomorphine and the other with an acid neutralizer to improve absorption and reduce oral irritation. Compared with Apokyn, APL-130277 is less likely to induce nausea due to a more gradual absorption.

The new drug application for APL-130277, first filed in April 2018, was supported by a 12-week, double-blind Phase 3 trial (NCT02469090). The results showed that, within 30 minutes of dosing, APL-130277 induced a clinically meaningful reduction in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part 3 score, a measure of Parkinson’s motor symptoms, in comparison with placebo.

The benefits were seen as early as 15 minutes after dosing and were maintained for 90 minutes. Improvements were still detected at weeks four, eight and 12. A higher percentage of patients achieved a full-on response — or control of motor symptoms — within 30 minutes with APL-130277.

“OFF episodes in people with Parkinson’s disease can occur at any point throughout the day, often occurring in the morning after awakening and periodically throughout the day and can disrupt the ability to perform everyday activities,” Antony Loebel, MD, president and CEO at Sunovion, said in a press release.

“We look forward to continuing our dialogue with the FDA during the review period with the intention of bringing a much needed on-demand treatment option for OFF episodes to those living with Parkinson’s disease.”

An ongoing open-label extension study (NCT02542696) is testing the safety and tolerability of APL-130277 when used in the long-term. The trial is still recruiting at Los Angeles and at some European sites. More information can be found here.

The post Sunovion Re-Submits Approval Request for APL-130277 to FDA for Treating Parkinson’s Off Periods appeared first on Parkinson’s News Today.