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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.

Study examines links of age, smoking, and physical activity with Parkinson’s

November 1, 2018 Education, Exercise

A new study published in the European Journal of Preventive Cardiology examines the links of age, smoking and physical activity as factors associated with Parkinson’s.

Previous studies have examined the link between physical activity and Parkinson’s, but the findings were inconclusive because of difficulties interpreting the results.

Researchers from the Technical University of Munich, Germany, and the Stanford University School of Medicine, US, assessed how physical activity and lifestyle factors impact the development of Parkinson’s.

They invited 7347 male veterans from the Veterans Exercise Testing Study (VETS) – an ongoing physical evaluation program – to take part in the study. The average age of those who took part was 59.

During the period of the study – which was 12 years on average – 94 participants or 1.3% of those studied had developed Parkinson’s.

Researchers found that high physical fitness, current smoking and younger age were associated with a lower incidence of Parkinson’s disease.

Commenting on the study, researchers said: “These findings parallel those of several epidemiological studies focusing on physical activity and the onset of Parkinson’s disease. Together, these observations provide strong support for recommending physical activity to diminish the risk of Parkinson’s disease.”

View the full study from the European Journal of Preventive Cardiology here.

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.

Could caffeine in the blood help diagnose Parkinson’s?

March 1, 2018 Life, Research

Blood caffeine levels could be promising diagnostic biomarkers for early-stage Parkinson’s, Japanese researchers reported in the journal ‘Neurology’ earlier this month.

The study found that people with Parkinson’s had lower levels of caffeine and caffeine metabolites in their blood than people without the disease, at the same consumption rate.

Caffeine concentrations also were decreased in Parkinson’s patients with motor fluctuations than in those without Parkinson’s. However, patients in more severe disease stages did not have lower caffeine levels.

The study’s authors, Dr David Munoz, University of Toronto, and Dr Shinsuke Fujioka, Fukuoka University, suggested that the “decrease in caffeine metabolites occurs from the earliest stages of Parkinson’s.”

They added: “If a future study were to demonstrate similar decreases in caffeine in untreated patients with Parkinson’s […] the implications of the current study would take enormous importance.”

Article from Parkinson’s Life.

Brain Rewiring in PD May Contribute to Abnormal Movement

October 1, 2017 Education, Research

The brain’s own mechanisms for dealing with the loss of dopamine neurons in Parkinson’s disease may be a source of the disorder’s abnormal movement, according to a Northwestern Medicine study published in Neuron.

The study suggests the loss of dopamine may cause the brain to rewire in a maladaptive manner, contributing to impaired movement in Parkinson’s disease. These findings also suggest that there are fundamental problems with scientists’ traditional model of Parkinson’s disease, said senior author Mark Bevan, PhD, professor of Physiology.

The prevailing consensus was that excessive patterning of the subthalamic nucleus (STN), a component of the basal ganglia, by the cerebral cortex was linked to the symptomatic expression of Parkinson’s disease, including muscle rigidity and slowness of movement, according to Bevan.

“When one saw a burst of activity in the cortex that was consistently followed by an abnormal burst of activity in the STN, scientists assumed that the direct connection between the two was responsible,” Bevan said.

Thus, Bevan and his colleagues, including lead author Hong-Yuan Chu, PhD, a post-doctoral fellow in the Bevan Lab, expected to see transmission in the cortex-to-STN pathway increase as dopamine levels dropped. Instead, they found the opposite: the strength of the pathway decreased massively.

“Like most scientists who come across something unexpected, we thought we’d done something wrong,” Bevan joked. “So, we used multiple, complementary approaches but everything pointed to the same conclusion.”

Further investigation suggested abnormal activity in a more indirect pathway from the cortex to the STN, involving the globus pallidus, was responsible. Abnormal activity in the indirect pathway leaves the STN vulnerable to excessive excitation, triggering compensatory plasticity that ultimately proved to be harmful, according to the study.

When the scientists prevented this maladaptive plasticity in late-stage Parkinson’s models, they found the symptoms improved, pointing to a link between compensation and motor dysfunction.

“According to the classic model, these adaptations should be homeostatic and preserve STN function,” Bevan said. “Preventing them should make the symptoms much worse — but it made them better instead.”

While the compensatory mechanisms may initially keep the brain operating normally under conditions of moderate dopamine neuron loss, as the disease progresses and more dopamine neurons die, the adaptations may become so extreme that they impair movement, according to the study.

These results suggest that there are fundamental flaws in our traditional understanding of brain dysfunction in Parkinson’s disease, Bevan said.

For Bevan, the unexpected results in this study served as a reminder that scientists must remain open-minded.

“It’s easy to be emotional and cling to your hypothesis,” Bevan said. “You have to be dispassionate, open-minded, and look at the data — if the data is not consistent with the hypothesis then you have to reject it and come up with a new one.”

This study was funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke grants 2R37 NS041280, P50 NS047085, 5T32 NS041234, and F31 NS090845. Confocal imaging work was performed at the Northwestern University Center for Advanced Microscopy, which was supported by National Cancer Institute Cancer Center Support grant P30 CA060553.

Article from Northwestern.edu.

Next Stop for PD Research: Outer Space

September 1, 2017 Life, Research

In an effort to find new treatments for Parkinson’s disease, researchers are sending their experiments to space.

On Monday Aug. 14, researchers launched a key Parkinson’s disease protein, called LRRK2, to the International Space Station (ISS). The microgravity conditions in space should offer a better test environment for their experiments with this protein, the researchers said.

The materials for their experiments will travel aboard the SpaceX Dragon capsule as part of a mission to send supplies and science experiments to the ISS.

The work is a collaboration between The Michael J. Fox Foundation for Parkinson’s Research and the Center for the Advancement of Science in Space (CASIS).

LRRK2 is a type of protein that modifies other proteins. Mutations in the gene that codes for LRRK2 are thought to cause Parkinson’s disease in some people. Researchers have hypothesized that developing drugs to inhibit LRRK2, or block its activity, could help prevent Parkinson’s or slow its progression.

But before scientists can develop a drug to inhibit LRRK2, they need to know the precise structure of this protein. One way to get a detailed view of its structure is by growing crystals of LRRK2 in lab dishes. However, on Earth, gravity can interfere with the growth of these crystals, and keep them small.

“The quality of our crystals is just not good enough [on Earth],” Sebastian Mathea, a researcher at the University of Oxford who is involved in the LRRK2 project, said during a news conference about the project Tuesday (Aug. 8).

This is where the ISS research comes in: Researchers hope that the microgravity conditions in space will allow the crystals to grow bigger with fewer defects. The scientists can then get a sharper view of the crystal structure.

Scientists will grow the LRRK2 crystals for about a month in space. Then, the crystals will be sent back to Earth, where they will be analyzed with high-energy X-rays, Mathea said.

Parkinson’s disease is a progressive neurological disorder that affects people’s movement abilities, and can result in symptoms such as tremors, slowed movements and muscle stiffness. There are currently no treatments to stop or reverse the progression of the disease, according to The Michael J. Fox Foundation.

Article from Live Science.

UW Otolaryngology Research Study

August 1, 2017 Research

Have you been diagnosed with Parkinson’s disease within the last 5 years, and are your motor symptoms mild? Dr. Timothy McCulloch’s research lab at the University of Wisconsin Hospital is recruiting subjects for a study evaluating changes to chewing, swallowing, voice, fine motor, and walking function in the early stages of Parkinson’s disease, as well as healthy controls.

Participation in this study lasts about 2 hours and participants are paid $60. Contact study coordinator Dr. Suzan Abdelhalim at 608-265- 2470 or [email protected] for more information.

Statins may not be used for protection against Parkinson’s disease

July 1, 2017 Education, Research

Use of statins may speed up the onset of Parkinson’s disease symptoms in people who are susceptible to the disease, according to Penn State College of Medicine researchers.

Some previous research has suggested that statins, used to treat high cholesterol, may protect against Parkinson’s disease. Research findings have been inconsistent, however, with some studies showing a lower risk, some showing no difference and some showing a higher risk of Parkinson’s disease in statin users.

“One of the reasons that may have explained these prior inconsistent results is that higher cholesterol, the main indication to use statins, has been related to lower occurrence of Parkinson’s disease,” said Xuemei Huang, professor of neurology. “This made it hard to know if the statin protective effect was due to the drug or preexisting cholesterol status.”

Another reason for the inconsistent results is that there are two types of statins. Water-soluble statins cannot get into the brain, while fat-soluble statins, called lipophilic, can. Since people with high cholesterol are treated for both kinds, the interpretation of results as it relates to Parkinson’s disease is not easy.

The researchers analyzed data in a commercially-available database of insurance claims for more than 50 million people. They identified nearly 22,000 people with Parkinson’s disease, and narrowed the number to 2,322 patients with newly diagnosed Parkinson’s disease. They paired each Parkinson’s patient with a person in the database who did not have Parkinson’s — called a control group. Researchers then determined which patients had been taking a statin and for how long before Parkinson’s disease symptoms appeared. Researchers reported their results in the journal Movement Disorders.

After analyzing the data, researchers found that prior statin use was associated with higher risk of Parkinson’s disease and was more noticeable during the start of the drug use.

“Statin use was associated with higher, not lower, Parkinson’s disease risk, and the association was more noticeable for lipophilic statins, an observation inconsistent with the current hypothesis that these statins protect nerve cells,” Huang said. “In addition, this association was most robust for use of statins less than two-and-a-half years, suggesting that statins may facilitate the onset of Parkinson’s disease.”

Guodong Liu, assistant professor of public health sciences, said, “Our analysis also showed that a diagnosis of hyperlipidemia, a marker of high cholesterol, was associated with lower Parkinson’s disease prevalence, consistent with prior research. We made sure to account for this factor in our analysis.”

A recent study reported that people who stopped using statins were more likely to be diagnosed with Parkinson’s disease, a finding interpreted as evidence that statins protect against Parkinson’s disease.

“Our new data suggests a different explanation,” Huang said. “Use of statins may lead to new Parkinson’s disease-related symptoms, thus causing patients to stop using statins.”

Huang stressed that more research needs to be completed and that those on statins should continue to take the medication their health care provider recommends.

“We are not saying that statins cause Parkinson’s disease, but rather that our study suggests that statins should not be used based on the idea that they will protect against Parkinson’s,” Huang said. “People have individual levels of risk for heart problems or Parkinson’s disease. If your mom has Parkinson’s disease and your grandmother has Parkinson’s disease, and you don’t have a family history of heart attacks or strokes, then you might want to ask your physician more questions to understand the reasons and risks of taking statins.”

One limitation of this study was that the MarketScan data did not include Medicare patients, Medicaid patients or the uninsured. Also, because it was a private insurance sample, the patients were all under 65 years old, so the findings cannot be generalized to those who are older.

Other researchers on this study are Lan Kong and Douglas Leslie, Department of Public Health Sciences; Nicholas Sterling, Medical Scientist Training Program student; and Mechelle Lewis and Richard Mailman, Departments of Neurology and Pharmacology, all of Penn State College of Medicine; and Honglei Chen, Michigan State University.

The Center for Applied Studies in Health Economics and Penn State College of Medicine funded this research.

Could Parkinson’s Disease Start in the Gut?

June 1, 2017 Education, Life, Research

Parkinson’s disease may start in the gut and spread to the brain via the vagus nerve, according to a study published in the April 26, 2017, online issue of Neurology^®, the medical journal of the American Academy of Neurology. The vagus nerve extends from the brainstem to the abdomen and controls unconscious body processes like heart rate and food digestion.

The preliminary study examined people who had resection surgery, removing the main trunk or branches of the vagus nerve. The surgery, called vagotomy, is used for people with ulcers. Researchers used national registers in Sweden to compare 9,430 people who had a vagotomy over a 40-year period to 377,200 people from the general population. During that time, 101 people who had a vagotomy developed Parkinson’s disease, or 1.07 percent, compared to 4,829 people in the control group, or 1.28 percent. This difference was not significant.

But when researchers analyzed the results for the two different types of vagotomy surgery, they found that people who had a truncal vagotomy at least five years earlier were less likely to develop Parkinson’s disease than those who had not had the surgery and had been followed for at least five years. In a truncal vagotomy, the nerve trunk is fully resected. In a selective vagotomy, only some branches of the nerve are resected.

A total of 19 people who had truncal vagotomy at least five years earlier developed the disease, or 0.78 percent, compared to 3,932 people who had no surgery and had been followed for at least five years, at 1.15 percent. By contrast, 60 people who had selective vagotomy five years earlier developed Parkinson’s disease, or 1.08 percent. After adjusting for factors such as chronic obstructive pulmonary disease, diabetes, arthritis and other conditions, researchers found that people who had a truncal vagotomy at least five years before were 40 percent less likely to develop Parkinson’s disease than those who had not had the surgery and had been followed for at least five years.

“These results provide preliminary evidence that Parkinson’s disease may start in the gut,” said study author Bojing Liu, MSc, of the Karolinska Instituet in Stockholm, Sweden. “Other evidence for this hypothesis is that people with Parkinson’s disease often have gastrointestinal problems such as constipation, that can start decades before they develop the disease. In addition, other studies have shown that people who will later develop Parkinson’s disease have a protein believed to play a key role in Parkinson’s disease in their gut.”

The theory is that these proteins can fold in the wrong way and spread that mistake from cell to cell.

“Much more research is needed to test this theory and to help us understand the role this may play in the development of Parkinson’s,” Liu said. Additionally, since Parkinson’s is a syndrome, there may be multiple causes and pathways.

Even though the study was large, Liu said one limitation was small numbers in certain subgroups. Also, the researchers could not control for all potential factors that could affect the risk of Parkinson’s disease, such as smoking, coffee drinking or genetics.

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, the Parkinson Research Foundation in Sweden, and the U.S. National Institutes of Health.

To learn more about Parkinson’s disease, visit www.aan.com/patients.

The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with 32,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+, LinkedIn and YouTube.

http://www.newswise.com/articles/could-parkinson-s-disease-start-in-the-gut

How gut bacteria affect PD treatment

Study examines links of age, smoking, and physical activity with Parkinson’s

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

Could caffeine in the blood help diagnose Parkinson’s?

Brain Rewiring in PD May Contribute to Abnormal Movement

Next Stop for PD Research: Outer Space

UW Otolaryngology Research Study

Statins may not be used for protection against Parkinson’s disease

Could Parkinson’s Disease Start in the Gut?

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Could Parkinson’s Disease Start in the Gut?