Research

Radical PD treatment tested in patients

March 1, 2019 Life, Research

A radical Parkinson’s treatment that delivers a drug directly to the brain has been tested in people.

Patients in the trial were either given the drug, which is administered via a “port” in the side of the head, or a dummy treatment (placebo). Both groups showed improved symptoms, meaning it was not clear if the drug was responsible for the benefits. However, scans did find visual evidence of improvements to affected areas of the brain in those given the drug. The study’s authors say it hints at the possibility of “reawakening” brain cells damaged by the condition.

Other experts, though, say it is too early to know whether this finding might result in improvements in Parkinson’s symptoms. Researchers believe the port implant could also be used to administer chemotherapy to those with brain tumours or to test new drugs for Alzheimer’s and stroke patients.

Parkinson’s causes parts of the brain to become progressively damaged, resulting in a range of symptoms, such as involuntary shaking and stiff, inflexible muscles. About 145,000 people in the UK have been diagnosed with the degenerative condition, which cannot be slowed down or reversed.

For this new study, scientists gave patients an experimental treatment called glial cell line-derived neurotrophic factor (GDNF), in the hope it could regenerate dying brain cells and even reverse the condition. Participants underwent robot-assisted surgery to have four tubes placed into their brains, which allowed GDNF to be infused directly to the affected areas with pinpoint accuracy, via a port in their head.

After an initial safety study of six people, 35 patients took part in a nine-month “blinded” trial, where half were randomly assigned to receive monthly infusions of GDNF and the other half dummy infusions.

Dr Alan Whone, principal investigator, said patients in the trial had, on average, been diagnosed eight years previously, but brain scans of those given the drug showed images that would be expected just two years after diagnosis.

He said: “We’ve shown with the Pet [positron emission tomography] scans that, having arrived, the drug then engages with its target, dopamine nerve endings, and appears to help damaged cells regenerate or have a biological response.”

Tom Phipps, 63, from Bristol, said he had noticed an improvement during the trial and had been able to reduce the drugs he takes for his condition. Since it ended, he has slowly increased his medication but is continuing to ride his bike, dig his allotment and chair his local branch of Parkinson’s UK.

“My outcome was as positive as I could have wished for,” he said. “I feel the trial brought me some time and has delayed the progress of my condition. The best part was absolutely being part of a group of people who’ve got a similar goal – not only the team of consultants and nurses but also the participants.

“You can’t have expectations – you can only have hope.”

Following the initial nine months on GDNF or placebo, all participants had the opportunity to receive GDNF for a further nine months.

By 18 months, when all participants had received GDNF, both groups showed moderate to large improvements in symptoms compared with their scores before they started the study. But the authors say the results need to be treated with caution because of the possibility of the placebo effect – when a patient feels better despite taking a medicine with no active ingredient.

Researchers hope that further trials could look at increasing the doses of GDNF or the duration of treatment.

Experts said it was “disappointing” that the difference in symptoms was not significant. But they said the study was still of “great interest” and warranted follow up research.

The findings from the trials are published in the medical journals Brain and the Journal of Parkinson’s Disease.

The study also features in a two-part BBC Two documentary series, The Parkinson’s Drug Trial: A Miracle Cure? on 28 February and 7 March, at 21:00. (Viewable only from the UK.)

Article from BBC.

How gut bacteria affect PD treatment

February 1, 2019 Education, Research

Patients with Parkinson’s disease are treated with levodopa, which is converted into dopamine, a neurotransmitter in the brain. In a study published on 18 January in the journal Nature Communications, scientists from the University of Groningen show that gut bacteria can metabolize levodopa into dopamine. As dopamine cannot cross the blood-brain barrier, this makes the medication less effective – even in the presence of inhibitors that should prevent the conversion of levodopa.

‘It is well established that gut bacteria can affect the brain’, explains Assistant Professor in Microbiology Sahar El Aidy, lead investigator of the study. ‘There is a continuous chemical dialogue between gut bacteria and the brain, the so called gut-brain axis.’ El Aidy and her team investigated the ability of gut microbiota to influence the bioavailability of levodopa, a drug used in the treatment of Parkinson’s disease.

The drug is usually taken orally, and the levodopa is absorbed in the small intestine and then transported through the blood stream to the brain. However, decarboxylase enzymes can convert levodopa into dopamine. In contrast to levodopa, dopamine cannot cross the blood-brain barrier, so patients are also given a decarboxylase inhibitor. ‘But the levels of levodopa that will reach the brain vary strongly among Parkinson’s disease patients, and we questioned whether gut microbiota were playing a role in this difference’, says El Aidy.

In bacterial samples from the small intestines of rats, Aidy’s PhD student Sebastiaan van Kessel found activity of the bacterial tyrosine decarboxylase enzyme, which normally converts tyrosine into tyramine, but was found to also convert levodopa into dopamine. ‘We then determined that the source of this decarboxylase was Enterococcus bacteria.’ The researchers also showed that the conversion of levodopa was not inhibited by a high concentration of the amino acid tyrosine, the main substrate of the bacterial tyrosine decarboxylase enzyme.

As Parkinson’s patients are given a decarboxylase inhibitor, the next step was to test the effect of several human decarboxylase inhibitors on the bacterial enzyme. ‘It turned out that, for example, the inhibitor Carbidopa is over 10,000 times more potent in inhibiting the human decarboxylase’, says El Aidy.

These findings led the team to the hypothesis that the presence of bacterial tyrosine decarboxylase would reduce the bioavailability of levodopa in Parkinson’s patients. To confirm this, they tested stool samples from patients who were on a normal or high dose of levodopa. The relative abundance of the bacterial gene encoding for tyrosine decarboxylase correlated with the need for a higher dose of the drug. ‘As these were stool samples, and the levodopa is absorbed in the small intestine, this was not yet solid proof. However, we confirmed our observation by showing that the higher abundance of bacterial enzyme in the small intestines of rats reduced levels of levodopa in the blood stream’, explains El Aidy.

Another important finding in the study is the positive correlation between disease duration and levels of bacterial tyrosine decarboxylase. Some Parkinson’s disease patients develop an overgrowth of small intestinal bacteria including Enterococci due to frequent uptake of proton pump inhibitors, which they use to treat gastrointestinal symptoms associated with the disease. Altogether, these factors result in a vicious circle leading to an increased levodopa/decarboxylase inhibitor dosage requirement in a subset of patients.

El Aidy concludes that the presence of the bacterial tyrosine decarboxylase enzyme can explain why some patients need more frequent dosages of levodopa to treat their motor fluctuations. ‘This is considered to be a problem for Parkinson’s disease patients, because a higher dose will result in dyskinesia, one of the major side effects of levodopa treatment.’

Article from University of Groningen.

Experimental cancer drug repurposed for Parkinson’s

December 1, 2018 Education, Research

As promising as a drug candidate may be, the unfortunate truth is that not all of them end up performing as hoped – but that doesn’t mean they’re completely useless. Researchers at Oxford University have managed to give second life to an experimental cancer drug known as tasquinimod, which has now shown promise for Parkinson’s.

Tasquinimod emerged as a promising drug in fighting solid tumors, with most research focusing on using it to treat prostate cancer. The drug made it through to phase three clinical trials, but unfortunately it didn’t seem to extend overall survival rates in patients, and after those disappointing results development was discontinued for prostate cancer treatment.

But the work wasn’t for nothing – the clinical trials so far have shown that tasquinimod is well tolerated by the body, and it could still potentially help treat other illnesses, such as Parkinson’s disease.

To investigate the drug, the Oxford team first took skin cells from patients with a rare genetic form of Parkinson’s, and turned them into a type of stem cell known as induced pluripotent stem cells (iPS). From these the researchers grew brain cells in vitro, allowing them to observe progression of the disease in the lab.

The team found that the key may be an error with a protein known as HDAC4. When that happens, this protein begins to repress certain genes, which in turn messes with the brain cells’ ability to regulate the natural cycle of proteins. That means those proteins build up in the cells, which has long been known to contribute to Parkinson’s and related neurodegenerative diseases like Alzheimer’s.

Tasquinimod comes to the rescue by blocking HDAC4, meaning those key genes aren’t “switched off,” and effectively halting progression of the disease.

“We think that switching off these genes in brain cells may play a vital role in the cell damage and death that occurs in Parkinson’s,” says Richard Wade-Martins, co-lead author of the study. “Finding a way to ‘turn them back on’ with a drug could be a promising, unexplored way to develop new treatments.”

The researchers then repeated the study using iPS cells gathered from people with the more common non-genetic form of Parkinson’s, and found that the same pattern of inactive genes seems to be at play. That indicates that these people might also benefit from the treatment, although the team also acknowledges that some people don’t seem to respond to it.

“The study also highlights the growing number of drugs which can be repurposed from their original medical use to treat Parkinson’s,” says David Dexter, Deputy Director of Research at Parkinson’s UK, which funded the study. “Developing a drug from scratch is a long, slow and expensive process. By finding existing drugs and moving them rapidly into clinical trials, we can make them available for people with Parkinson’s much more quickly, easily and cheaply.”

Although that process may be streamlined, it is still early days for tasquinimod. The study has only been conducted on a total of 10 patients so far, so more testing will need to be done before it could become a viable treatment option.

The research was published in the journal Cell Stem Cell.

Article from New Atlas.

Parkinson’s to be included in new CDC database

December 1, 2018 Research

Throughout the year, you’ve heard about a new database at the Centers for Disease Control (CDC) to collect vital demographic information on people living with neurological diseases. Earlier this fall, Congress gave the CDC funds to implement this database, called the National Neurological Conditions Surveillance System (NNCSS). The CDC recently announced that Parkinson’s is one of two diseases that will be included in the initial rollout of the NNCSS.

While there are rough estimates of the number of people diagnosed with Parkinson’s in the United States, we don’t have accurate and comprehensive information on how many people are living with the disease, who they are and where they are located. This lack of core knowledge can slow Parkinson’s research and therapeutic development. The NNCSS will be a valuable resource for collecting this information. The data could help scientists understand many aspects of the disease, such as clusters of diagnoses in certain geographic regions, differences in the number of men and women diagnosed with Parkinson’s, and variability in health care practices among patients.

Establishing the NNCSS will provide researchers with critical information on the impact of Parkinson’s disease in the United States. Through WPA’s participation in the Unified Parkinson’s Advocacy Council, we will offer the CDC information on Parkinson’s and the role the NNCSS can play in helping to further research. As the CDC releases updates about the database, we will share news with you.

Irish entrepreneur uses technology to fight PD

October 1, 2018 Community Outreach, Life, Research

Ciara Clancy is no ordinary entrepreneur, with her company Beats Medical far less concerned with making money than it is with helping people live with various neurological conditions.

At the age of just 29, Ciara Clancy’s work in helping people to live with the likes of Parkinson’s disease, Alzheimer’s, dyspraxia and the effects of stroke are unparalleled on the island of Ireland.

Speaking to host Tadhg Enright on this week’s The Architects of Business, in partnership with EY Entrepreneur Of The Year™, Ciara reveals the reason why she left behind her career as a physiotherapist.

A highly driven and passionate individual, Ciara wanted to create technology – based on Metronome Therapy, which helps Parkinson’s sufferers in particular – that would make it as easy for those living with these life-changing conditions to get around at home as it would be under medical supervision.

“I remember the exact moment that I decided I wanted to found Beats Medical,” Ciara – a 2016 finalist in the EY Entrepreneur Of The Year™ programme – reveals.

“A person with Parkinson’s disease was coming into me for this Metronome Therapy in a hospital, and he was 20 minutes late and I went out to find him stuck, frozen at the main entrance.

“And this was happening everywhere we went, every door he went through, and I knew that when he came into clinic he walked very well with Metronome Therapy but he’d go home and this would persist, and it was at that point I said I can’t go 20 years into my career and not try. I need to find a way to bring this treatment into the home.

“That’s when I decided to step out of my career as a physio and volunteer with a Parkinson’s charity to understand needs outside of the hospital. And really that’s how Beats Medical was born.”

Article from JOE.ie.

Study Reveals Mechanisms Underlying Pain Processing in PD

October 1, 2018 Education, Life, Research

Parkinson’s disease is a condition affecting the human brain that becomes worse over time. The most common symptoms are tremors, muscle spasms and movements that are much slower than normal; all of which decrease an individual’s quality of life. Although there is currently no cure, the brain structures involved in Parkinson’s disease are known. These are collectively termed the basal ganglia, and are often targeted to treat the symptoms of Parkinson’s disease. For example, electrically stimulating the subthalamic nucleus (STN), one part of the basal ganglia, reduces muscle tremors and stiffness.

Pain is another common symptom in Parkinson’s disease. Patients often report strange burning or stabbing sensations with no obvious physical cause. They are also likely to be more sensitive to painful stimuli and have a lower pain threshold than normal. This suggested that the brain circuits that allow us to perceive and process pain could be somehow involved in Parkinson’s disease. Indeed, stimulating the STN is known to relieve pain in Parkinson’s disease, as well as the muscle symptoms, but exactly how the STN might link up with the brain’s ‘pain network’ remains poorly understood. Pautrat et al. therefore set out to explore the connection between pain networks and the STN, and determine its potential role in Parkinson’s disease.

First, the electrical activity of nerve cells in the STN of rats was measured, which revealed that these cells do respond to mildly painful sensations. Experiments using dyes to label cells in both the STN and brain structures known to transmit painful signals showed that the STN was indeed directly linked to the brain’s pain network. Moreover, rats with a STN that did not work properly also responded abnormally to painful stimuli, confirming that the STN did indeed influence their perception of pain. Finally, Pautrat et al. repeated their measurements of electrical activity in the STN, this time using rats that lacked the same group of nerve cells affected in the basal ganglia of patients with Parkinson’s disease. Such rats are commonly used to model the disease in laboratory experiments. In these rats, the STN cells responded very strongly to painful stimuli, suggesting that problems with the STN could be causing some of the pain symptoms in Parkinson’s disease.

This work reveals a new role for the STN in controlling responses to pain, both in health and disease. Pautrat et al. hope that their results will inspire research into more effective treatments of nerve pain in both Parkinson’s disease and other neurodegenerative conditions.

To learn more about this work, visit elifesciences.org.

Protein might become candidate for drug development

October 1, 2018 Research

Researchers have modified the protein Nurr1 so that it can enter cells from the outside. Nurr1 deficiency may be one of the causes of Parkinson’s disease. Even though Nurr1 has been discussed as a potential target for the treatment of Parkinson’s disease, it is unusable in its normal form, as it cannot penetrate cells. A team from Ruhr-Universität Bochum and the US-American National Institutes of Health (NIH) deployed a bacterial import signal in order to deliver Nurr1 into cells. The researchers also demonstrated that the modified protein may have a positive effect on the survival of dopamine-producing nerve cells. They describe their results in the journal Molecular Neurobiology from 18 August 2018.

For the study, Dennis Paliga, Fabian Raudzus, Dr. Sebastian Neumann, and Professor Rolf Heumann from the work group Molecular Neurobiochemistry collaborated with Professor Stephen Leppla from the NIH.

Bacterial protein building block as import signal

Nurr1 is a transcription factor; this means the protein binds to DNA in the nucleus and regulates which genes get read and translated into proteins. Thereby, it controls many properties in cells that produce the neurotransmitter dopamine and that are affected in Parkinson’s disease. Dopamine withdrawal in certain brain regions is responsible for the slowness of movement that is associated with the disease.

Since the Nurr1 protein does not usually have the capability of entering cells and, therefore, cannot take effect in the nucleus, the researchers were searching for ways of furnishing the protein with an import signal. They found what they were looking for in bacteria and attached a fragment of a protein derived from Bacillus anthracis to Nurr1. In the bacterium, that protein ensures that the pathogen can infiltrate animal cells. “The fragment of bacterial protein that we used does not trigger diseases; it merely contains the command to transport something into the cell,” explains Rolf Heumann. Once the modified protein has been taken up by the cell, the bacterial protein building block is detached, and the Nurr1 protein can reach its target genes by using the cell’s endogenous nuclear import machinery.

Nurr1 has a positive effect on the key enzyme of dopamine synthesis

The researchers measured the effect of functional delivery of Nurr1 by monitoring the production of the enzyme tyrosine hydroxylase. That enzyme is a precursor in dopamine synthesis – a process that is disrupted in Parkinson’s patients. Cultured cells that were treated with modified Nurr1 produced more tyrosine hydroxylase than untreated cells. At the same time, they produced less Nur77 protein, which is involved in the regulation of programmed cell death.

Protein protects from the effects of neurotoxin

Moreover, the researchers tested the effect of modified Nurr1 on cultured cells that they treated with the neurotoxin 6-hydroxydopamine. It causes the dopamine-producing cells to die and is thus a model for Parkinson’s disease. Nurr1 inhibited the neurotoxin-induced degeneration of cells.

“We hope we can thus pave the way for new Parkinson’s therapy,” concludes Sebastian Neumann. “Still, our Nurr1 fusion protein can merely kick off the development of a new approach. Many steps still remain to be taken in order to clarify if the modified protein specifically reaches the right cells in the brain and how it could be applied.”

Article from Ruhr University Bochum.

Characterization of Parkinson Disease With Restlessness

October 1, 2018 Education, Life, Research

Highlights

A study was conducted of restless leg syndrome, leg motor restlessness, and their variants in Parkinson disease and related disorders.
A total of 49.2% of PD patients had any restlessness, including RLS and LMR.
LMR variants and RLS variants are rare in PD and related disorders.
PD with restlessness was related to autonomic, sleep and depressive symptoms.

Objective
The objective of this study was to investigate the prevalence of restless leg syndrome (RLS), leg motor restlessness (LMR) and RLS/LMR variants and their relationship with clinical factors in patients with Parkinson’s disease (PD) and related disorders.

Methods
Sixty-three PD patients, 17 multiple system atrophy (MSA) patients and 11 progressive supranuclear palsy (PSP) patients were included in this study. Through face-to-face interviews, the patients were diagnosed with RLS/LMR, or with RLS/LMR variants in which the symptoms occur predominantly in body parts other than the legs.

Results
The frequency of RLS, LMR, RLS variants and LMR variants was as follows: PD (12.7%, 11.1%, 0% and 1.6%); MSA (5.9%, 11.8%, 0% and 0%); and PSP (0%, 9.1%, 0% and 0%). Restlessness without the urge to move was observed in 25.4% of the PD patients, 11.8% of the MSA patients and 0% of the PSP patients. The PD patients with restlessness exhibited higher Hoehn and Yahr stages and higher scores on the Scales for Outcomes in PD-Autonomic, PD sleep scale-2 and Beck Depression Inventory-II. The olfactory functioning, 123I-MIBG myocardial scintigraphy uptake and dopamine transporter single photon emission computed tomography findings did not differ between the PD patients with restlessness and those without. The severity of RLS was correlated with the autonomic symptoms among the PD patients with restlessness.

Conclusion
PD with restlessness was characterized by increased autonomic, sleep and depressive symptoms. Further studies including a large sample are warranted to characterize restlessness in PD and related disorders.

Information from Journal of the Neurological Sciences.

The eyes may have it, an early sign of Parkinson’s disease

September 1, 2018 Research

The eyes may be a window to the brain for people with early Parkinson’s disease. People with the disease gradually lose brain cells that produce dopamine, a substance that helps control movement. Now a new study has found that the thinning of the retina, the lining of nerve cells in the back of the eye, is linked to the loss of such brain cells. The study is published in the August 15, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“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,” said study author Jee-Young Lee, MD, PhD, of the Seoul Metropolitan Government – Seoul National University Boramae Medical Center in South Korea. “We also found the thinner the retina, the greater the severity of disease. 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.”

The study involved 49 people with an average age of 69 who were diagnosed with Parkinson’s disease an average of two years earlier but who had not yet started medication. They were compared to 54 people without the disease who were matched for age.

Researchers evaluated each study participant with a complete eye exam as well as high-resolution eye scans that use light waves to take pictures of each layer of the retina. In addition, 28 of the participants with Parkinson’s disease also had dopamine transporter positron emission tomography (PET) imaging to measure the density of dopamine-producing cells in the brain.

Researchers found retina thinning, most notably in the two inner layers of the five layers of the retina, in those with Parkinson’s disease. For example, for those with Parkinson’s disease, the inner most layer of the retina in one section of the eye had an average thickness of 35 micrometers (?m) compared to an average thickness of 37 ?m for those without the disease.

In addition, the thinning of the retina corresponded with the loss of brain cells that produce dopamine. It also corresponded with the severity of disease. When disability from the disease is measured on a scale of one to five, the people with the most thinning of the retina, or thickness of less than 30 ?m, had average scores of slightly over two, while people with the least thinning, or thickness of about 47 ?m, had average scores of about 1.5.

“Larger studies are needed to confirm our findings and to determine just why retina thinning and the loss of dopamine-producing cells are linked,” said Lee. “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.”

A limitation of the study was that the retina scans focused only on a limited area of the retina. The study was also a snapshot in time and did not follow participants over a long period of time.

The study was supported by the Seoul Metropolitan Government – Seoul National University Boramae Medical Center and the Korean Ministry of Education, Science and Technology.

Information provided by American Academy of Neurology.

Contact sports increase Parkinson disease risk

August 1, 2018 Awareness, Life, Research

Injuries from playing contact sports, such as rugby, boxing, and martial arts, have been linked to a heightened risk of dementia. A new study now says that contact sports may actually lead to other neurodegenerative diseases, and it explains why.

At Medical News Today, we have covered studies linking brain injury — usually as a result of playing contact sports — with a higher risk of developing various conditions later in life.

One such study argued that brain injuries could accelerate the processes that bring about Alzheimer’s disease, which is the most common type of dementia. It is characterized most prominently by memory loss, a sense of disorientation, and an impaired ability to carry on a daily routine.

Numerous studies during the past few years have suggested that repeated head injuries obtained from participation in contact sports are linked to chronic traumatic encephalopathy (CTE), which is a degenerative brain disease that can lead to dementia.

Now, a study led by researchers from the Boston University School of Medicine in Massachusetts has found that people engaging in contact sports may also be more likely to develop Lewy body disease.

In that condition, a protein called alpha-synuclein forms abnormal deposits known as Lewy bodies in the brain. Lewy body disease is associated with dementia symptoms, as well as with Parkinson’s disease.

Traditionally, scientists have believed that the motor symptoms — such as tremors, slowness of movement, and difficulty walking — experienced by some athletes are attributable to CTE.

However, the researchers argue instead that those symptoms are actually a byproduct of Lewy body disease, independently of CTE.

“We found the number of years an individual was exposed to contact sports, including football, ice hockey, and boxing, was associated with the development of neocortical [Lewy body disease], and Lewy body disease, in turn, was associated with Parkinsonism and dementia,” says study author Dr. Thor Stein.

The researchers’ findings are now published in the Journal of Neuropathology and Experimental Neurology.

Risk increased in long-term sports players

Dr. Stein and team drew their conclusions after studying 694 donated brains from three sources: the Veteran’s Affairs-Boston University-Concussion Legacy FoundationBrain Bank, Boston University Alzheimer’s Disease Center, and the Framingham Heart Study.

They found that the total number of years that a person had spent playing contact sports was associated with an increased risk of developing Lewy bodies in the cerebral cortex.

People who participated in contact sports for over 8 years had the greatest risk of developing Lewy body disease — six times higher, in fact, than the increase in risk seen in people who had played contact sports for 8 years or under. Moreover, people who had both CTE and Lewy body disease had a higher risk of dementia and Parkinson’s than those who only had CTE.

These findings may not be surprising. After all, as the authors note, previous research had already shown that the number of years spent playing contact sports can be used to predict the severity of dementia-related pathology, as well as the severity of CTE in former players.

This research, the scientists add, builds on data provided by existing studies, though further efforts should be made to ascertain, with more exactitude, the health risks to which repeated brain injuries expose athletes.

“Future studies incorporating more participants with neocortical [Lewy body disease] and contact sports play will be necessary to more accurately determine the best threshold and risk of contact sports participation,” the researchers write.

Article from Medical News Today.

Radical PD treatment tested in patients

How gut bacteria affect PD treatment

Experimental cancer drug repurposed for Parkinson’s

Parkinson’s to be included in new CDC database

Irish entrepreneur uses technology to fight PD

Study Reveals Mechanisms Underlying Pain Processing in PD

Protein might become candidate for drug development

Characterization of Parkinson Disease With Restlessness

The eyes may have it, an early sign of Parkinson’s disease

Contact sports increase Parkinson disease risk

Risk increased in long-term sports players

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Contact sports increase Parkinson disease risk