Research offers new understanding about cause of Parkinson's disease

March 21, 2018

Until very recently, Parkinson's had been thought a disease that starts in the brain, destroying motion centers and resulting in tremors and loss of movement. New research published this week in the journal Brain, shows the most common Parkinson's gene mutation may change how immune cells react to generic infections like colds, which in turn trigger the inflammatory reaction in the brain that causes Parkinson's. The research offers a new understanding of Parkinson's disease.

"We know that brain cells called microglia cause the inflammation that ultimately destroys the area of the brain responsible for movement in Parkinson's," said Richard Smeyne, PhD, Director of the Jefferson Comprehensive Parkinson's Disease and Movement Disorder Center at the Vickie and Jack Farber Institute for Neuroscience. "But it wasn't clear how a common inherited mutation was involved in that process, and whether the mutation altered microglia."

Together with Dr. Smeyne, first author Elena Kozina, PhD, looked at the mutant version of the LRRK2 gene (pronounced 'lark'). Mutations in the LRRK2 gene are the most common cause of inherited Parkinson's disease and are found in 40 percent of people of North African Arab descent and 18 percent of people of Ashkenazi Jewish descent with Parkinson's. However there's been controversy around the exact function of the LRRK2 gene in the brain.

"We know that gene mutation is not enough to cause the disease," said Dr. Kozina, Post-Doctoral student at Jefferson (Philadelphia University + Thomas Jefferson University). "We know that twins who both carry the mutation, won't both necessarily develop Parkinson's. A second 'hit' or initiating event is needed."

Based on his earlier work showing that the flu might increase risk of Parkinson's disease, Dr. Smeyne decided to investigate whether that second hit came from an infection. Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent -- the outer shell of bacteria, called lippopolysaccharide (LPS) – that causes an immune reaction. LPS itself does not pass into the brain, nor do the immune cells it activates, which made it ideal for testing whether this second hit was acting directly in the brain.

When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a "cytokine storm," with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.

Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the brain region involved in movement.

"Although more tests are needed to prove the link, as well as testing whether the same is true in humans, these findings give us a new way to think about how these mutations could cause Parkinson's," said Dr. Smeyne. "Although we can't treat people with immunosuppressants their whole lives to prevent the disease, if this mechanism is confirmed, it's possible that other interventions could be effective at reducing the chance of developing the disease."

Source:

https://www.jefferson.edu/

https://www.news-medical.net/news/20180321/Research-offers-new-understanding-about-cause-of-Parkinsons-disease.aspx

Research could lead to new treatments for Parkinson's

Meredith Cohn - March 22, 2018

Dr. Lisa Shulman, neurologist at the University of Maryland Medical Center (University of Maryland Medical System)

When singer Neil Diamond announced in January that he would stop touring after being diagnosed with Parkinson’s disease, it brought new attention to the neurodegenerative disorder that can bring many different kinds of symptoms.

While there isn’t a cure, there are several means of treating the effects of the disease, from drugs to exercise.

And there are a lot of promising areas of research, according to Dr. Lisa Shulman, professor of neurology at the University of Maryland School of Medicine, director of the University of Maryland Parkinson’s Disease & Movement Disorder Center and a neurologist specializing in Parkinson’s disease and other movement disorders at the University of Maryland Medical Center.

What is Parkinson's and what causes it?

Parkinson’s disease is a type of neurodegenerative disorder. This means an area of a person’s brain is injured, and the injury progresses over time. In Parkinson’s disease, the part of the brain that controls movement is affected. Changes also have been found outside the brain in other regions of the body, even in the gastrointestinal tract.

We don’t yet have a clear answer for what causes Parkinson’s disease. We know that genetics play a part. But of the thousands of people living with Parkinson’s, the majority do not have other family members with the disease. Like many chronic conditions, genetics make a person vulnerable to Parkinson’s disease but not necessarily at high risk for developing it.

What does it do to a person over time?

Parkinson’s affects the brain’s ability to produce dopamine, which regulates movement and emotional responses. Most people associate Parkinson’s with a tremor, which many, but not all, people experience. It also causes a slowing down of movement, stiffness and loss of dexterity.

In addition to motor problems, Parkinson’s may cause cognitive changes, including problems with attention and multitasking. It may cause sleep disturbance, balance problems, constipation, fatigue and depression. Parkinson’s progresses very gradually; loss of balance and cognitive problems usually emerge many years after onset.

How are motor and non-motor symptoms treated?

Levodopa and other medicines that boost the dopamine system are effective for motor symptoms including tremor, slowness and stiffness. When it comes to non-motor symptoms, we have a whole toolbox of medications. Options are available to treat depression, anxiety, constipation and sleep. For many people, the most disabling parts of Parkinson’s disease are balance and cognitive problems, but effective treatments for these problems are yet to be discovered.

The last 20 years have brought important surgical options to treat Parkinson’s disease. Deep brain stimulation (DBS) surgery has become a standard of care to treat motor fluctuations. An electrode is placed deep inside the brain in a targeted area. The electrode is connected to a stimulator that is placed under the skin in the upper chest, similar to a pacemaker. DBS requires one or two burr holes in the skull, and electrodes are passed through the brain. It produces effects that are similar to taking levodopa medication and the effects are continuous. The complication rate is low; however, because it is a device, there can be complications, such as connection problems (electrodes and wires) and need for battery replacement.

Do non-pharmacologic treatments such as exercise slow progression of the disease?

One of the most important discoveries in the last 15 years has been that physical activity clearly benefits people with Parkinson’s. Both aerobic and muscle-strengthening exercises — treadmill, resistance, cycling, boxing, dancing and tai chi, to name a few — have all been shown effective and can improve walking. Aerobic exercise improves endurance, while resistance improves muscle strength — so people should be doing both. It is important to keep the heart rate up for 30 to 45 minutes to reap the benefits. With muscle strengthening, the goal is to progressively increase the weights over time.

What new treatments are on the horizon?

This is a promising time for Parkinson’s disease research because many novel approaches are being tested. For people with a recent Parkinson’s diagnosis, we are currently investigating an antibody that breaks down abnormal protein deposits in the brain. The hope is that this approach will prevent or delay disease progression. The University of Maryland Medical Center is one of the centers participating in this clinical trial.

MRI-guided focused ultrasound is a new approach that is simpler than DBS surgery. It is classified as surgery, but doesn’t involve cutting or implanted wires. Instead, a small lesion is made deep in the brain with ultrasound. As with DBS, the focused ultrasound procedure helps improve tremor, dyskinesia and motor fluctuation when medication isn’t effective. It potentially has fewer side effects than DBS. The procedure is currently FDA-approved for another medical condition called essential tremor, but not yet for Parkinson’s disease. We are conducting clinical trials at the University of Maryland Medical Center to investigate focused ultrasound for Parkinson’s.

To inquire about participating in clinical trials for Parkinson’s disease at the University of Maryland Medical Center, call Michelle Cines or Christina Griffin at 410-328-0157

http://www.baltimoresun.com/health/bs-hs-ask-the-expert-parkinsons-20180309-story.html

Noticing the Signs of Parkinson’s Disease in a Loved One

 MARCH 21, 2018 BY "SHERRI WOODBRIDGE"

This is written for loved ones who might have a sense that something isn’t quite right with the one they care about. It is a list of early signs you may notice before your spouse, friend, child, or parent does and how you might help them.

Most people notice the tremors as the first symptom of Parkinson’s disease (PD) in someone they know. However, did you know that there are other signs that are a clue that someone may have PD? Clues that are often overlooked, even by medical doctors?

On one of my earlier visits to my neurologist, I learned one of the first signs of PD can be depression. Looking back, it was true for me. There was no reason for me to feel down or anxious, but I did. I talked to my general practitioner about it, and she was the one who first put me on an antidepressant. There are many other reasons a person can feel depressed, so don’t jump to conclusions that the one you’re concerned about has PD. For a diagnosis to be confirmed, several symptoms must be present. A diagnosis of PD isn’t made solely because a person is depressed.

So, what if they have tremors and seem down? Again, there is a list of symptoms your neurologist will look for in making a correct diagnosis of PD. Adding tremors to the mix with depression will not necessarily mean Parkinson’s disease.

Is your mate having a hard time sleeping? Restless? Tired during the day from lack of a good night’s rest? Having vivid dreams? Nightmares? Acting out while dreaming? All on a regular basis? If you are married and find yourself wanting to go to the guest room frequently because your spouse is, how shall I put this, too active in bed? It may be a cause for concern. Sleep disorders can be evidence that something may be going on.

Parkinson’s can snitch your sniffer, so your loved one may not smell things as well or at all. The ability to smell may return for the short-term at random times, though.

PD can also cause a person to drag their foot or have a slight shuffle when they walk.

No one likes people to enter the room and ask, “What’s wrong with you?” But that can happen when early signs of PD show — such as the masked face. What is “masked” face? When the muscles in the face have tightened. Because of this, people with PD have a harder time smiling or showing facial emotion. It’s also been called a stone face — showing no expression. You’ve heard the saying, “Don’t judge a book by its cover.” Well, in PD we say, “Don’t judge the mood by the face.” OK, maybe only I have said that. But it’s true.

Another symptom I struggle(d) with is a soft voice. I have a soft voice to begin with, and getting softer only served to aggravate those around me. It also makes for lousy conversation on the part of the person with PD, as no one hears you participating in the conversation, so you end up being constantly interrupted, never able to finish your sentences. Plus, well, you just don’t feel like talking at all.

It takes several signs/symptoms to make a diagnosis of Parkinson’s disease, and it should be done by a neurologist or a movement disorder specialist. It’s important to remember that everyone lives with PD differently. Some are affected more by tremors, some by stiffness, some by pain, and some deal with it all. And some may have some of the signs, but don’t actually have PD. Don’t make your diagnosis. Ask questions until you are satisfied with the answers, and don’t give up. We’re in this together.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2018/03/21/signs-parkinsons-disease-what-look-before-diagnosis/

Mutation Plays a Role in Fatty Plaque Formation in Brain, Study Suggests

 MARCH 21, 2018    BY ALICE MELÃO 

A common Parkinson’s gene mutation plays a role in the formation of fatty plaque in the brain that can destroy nerve cells controlling movement, a study suggests.

The research, “GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers,” was published in the Proceedings of the National Academy of Sciences.

Five to 10 percent of Parkinson’s patients have a mutation of the GBA1 gene. It generates an enzyme responsible for breaking down a large fat molecule into smaller ones called ceramides.

Fat molecules are the glue that helps proteins maintain a complex design in cell membranes.   The GBA1 enzyme is supposed to ensure that the glue is strong enough to hold the mosaic together.

In addition to ensuring cell membrane integrity, the enzyme is also responsible for the normal functioning of the cell’s recycling system.

Johns Hopkins researchers used the gene editing technology CRISPR-Cas9 to remove the enzyme from lab-grown brain cells. As expected, its depletion led to an accumulation of a fatty molecule called glucosylceramide and increased cell stress.

Strikingly, when glucosylceramide levels rose, the number of stable alpha-synuclein tetramers — a hallmark of Parkinson’s disease — fell.

Researchers then treated the modified brain cells with Zavesca (miglustat), an approved therapy for the treatment of Gaucher disease type 1 that prevents fatty molecule buildups.

The treatment led to cells recovering their levels of alpha-synuclein tetramers. This suggested that high levels of glucosylceramide destabilize the cell membrane mix. The result is alpha-synuclein tetramers falling out of the mosaic and breaking into single alpha-synucleins, the researchers said.

To further assess the potential of targeting GBA1 to treat Parkinson’s, the team used brain cells collected from a patient with a mutated GBA1 gene. These cells had lower than normal GBA1 activity and higher than normal levels of glucosylceramide. The result was an  accumulation of alpha-synuclein monomers.

Once more, treatment with Zavesca promoted alpha-synuclein stability and tetramer formation, while preventing the accumulation of alpha-synuclein fibrils that is characteristic of Parkinson’s disease. In addition, the researchers showed that increasing the amount of functional GBA1 with gene therapy also promoted alpha-synuclein stability.

“We believe this study gives us a better understanding of the effects of GBA1 mutation and its role in the development and progress of Parkinson’s disease,” Dr. Han Seok Ko, an associate professor of neurology at the Johns Hopkins University School of Medicine’s  Institute for Cell Engineering, said in a press release.

The team plans to continue study the enzyme’s effect on alpha-synuclein and nerve cell health.

https://parkinsonsnewstoday.com/2018/03/21/parkinsons-mutation-fatty-brain-plaque-formation/

Lundbeck Acquires Rights to Develop Foliglurax Therapy Candidate to Treat Parkinson’s

MARCH 21, 2018  BY PATRICIA INACIO, PHD 

Lundbeck will acquire the biopharmaceutical Prexton Therapeutics, obtaining the development and commercialization rights to foliglurax (PTX002331), an investigational therapy currently in Phase 2 trials for Parkinson’s disease.

Foliglurax is a small molecule modulator that activates nerve cells with a set of specific glutamate receptors called mGluR4, and compensates for the lack of dopamine in the brain. Activating mGluR4 is expected to correct the impaired motor behaviors in Parkinson’s disease.

In preclinical studies with animal models of Parkinson’s disease, foliglurax showed positive effects in modulating the disease course. And in a Phase 1 clinical study (NCT02639221) with healthy volunteers, the treatment was found to be safe and well-tolerated.

In July 2017, Prexton launched a proof-of concept Phase 2 clinical trial (NCT03162874) called AMBLED to test foliglurax in Parkinson’s patients.

The AMBLED study, currently recruiting participants at 44 sites in six European countries, is a double-blind, randomized, placebo-controlled trial expecting to recruit 165 Parkinson’s patients who have previously been treated with a stable regimen of levodopa-containing therapy.

Patients will be randomized to one of two oral doses of foliglurax (10 mg or 30 mg), or a placebo, for 28 days.

The trial’s primary goal is to evaluate the effectiveness of the treatment candidate in reducing levodopa-induced motor complications, also known as levodopa-induced dyskinesia. This is a condition characterized by involuntary movements that usually occur after prolonged treatment with levodopa in Parkinson’s patients.

The study is expected to be completed in 2019.

“By acquiring Prexton, Lundbeck will obtain global rights to foliglurax, an exciting first-in-class compound, and gain full control of the asset,” Anders Götzsche, interim CEO and chief financial officer of Lundbeck, said in a press release.

“Foliglurax addresses high unmet needs with its potential indication in Parkinson’s, fitting perfectly within Lundbeck’s core areas and this treatment option also appears to be highly interesting for patients, physicians and payors,” he added.

https://parkinsonsnewstoday.com/2018/03/21/lundbeck-acquires-rights-develop-parkinsons-disease-therapy-candidate-foliglurax/

Biomarkers Identified That Could Help Predict Individuals at Risk for Parkinson’s, Study Says

MARCH 20, 2018  BY ALICE MELÃO

Low levels of two dopamine-related molecules in cerebrospinal fluid can help identify patients in the early stages of preclinical Parkinson’s disease, a study suggests.

The study, “Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson’s disease,” was published in Parkinsonism & Related Disorders.

Parkinson’s disease is mainly recognized by its motor symptoms, such as uncontrolled tremors, gait difficulties, and slow movement. However, by the time these symptoms appear, a significant loss of brain cells sensitive to dopamine has already occurred.

Because of this, there is a need for sensitive markers of early brain cell loss that can be used to track disease progression.

DOPAC and DOPA are two dopamine-related molecules whose levels are reduced in patients with untreated Parkinson’s. However, it was not clear if measuring levels of both proteins could help identify asymptomatic, healthy people who are at risk of developing Parkinson’s disease.

A team led by David Goldstein, MD, PhD, principal investigator at the National Institutes of Health, evaluated the levels of DOPAC and DOPA in cerebrospinal fluid samples collected from 26 at-risk people.

This analysis was integrated in the PDRisk prospective study of the National Institute of Neurological Disorders and Stroke (NINDS), which intends to identify early biomarkers of Parkinson’s disease.

Participants had to have at least three previously defined risk factors for Parkinson’s disease, including direct family history of the disease, loss of sense of smell, impaired sleep or abnormal sleep behavior, and low resting blood pressure.

Patients who were already showing signs of Parkinson’s-related motor symptoms during the enrollment phase were excluded from the study.

Of the 26 participants, four developed clinical Parkinson’s disease during the three-year follow-up period. These patients were found to have significantly lower levels of both DOPA and DOPAC in cerebrospinal fluid than the 22 participants who did not develop Parkinson’s for at least a mean follow-up of 4.2 years.

Researchers determined that the optimal cutoff value for defining low diagnostic DOPAC was 1.22 pmol/mL, which accurately predicted Parkinson’s risk in 84.1% of cases. For DOPA, the cutoff value was 2.63 pmol/mL, accurately predicting disease risk in 90.3% of cases.

These data suggest that early dopamine deficiency in at-risk individuals — defined by low DOPAC and DOPA levels — is linked to an increased likelihood of developing clinical Parkinson’s disease within three years.

Researchers believe the identified “predictive strength” reflects the important role of these neurochemical biomarkers in the underlying mechanisms of disease, suggesting that “neurochemical biomarkers of central dopamine deficiency identify the disease in a pre-clinical phase.”

https://parkinsonsnewstoday.com/2018/03/20/dopac-dopa-biomarkers-predict-parkinsons-disease-study/

In-Depth Data Set of Brain May Provide Key to Understanding Neurodegenerative Diseases

MARCH 20, 2018  BY ANA PENA 

A comprehensive data set of the human brain was developed by researchers at Emory University in Atlanta as a valuable resource likely to advance knowledge on the mechanisms behind both Parkinson’s (PD) and Alzheimer’s disease (AD). 

The data was published in a report titled, Global quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s Disease in the journal Scientific Data.

Alzheimer’s and Parkinson’s disease are the most common neurodegenerative diseases, and both share clinical and pathological features.

Observations at the cell level suggest these two diseases have common underlying mechanisms. Alzheimer’s and Parkinson’s rely on the accumulation of proteins that are folded incorrectly and become toxic to nerve cells and brain connections. 

In Parkinson’s, the misfolded protein that accumulates inside neurons is called alpha-synuclein, while in Alzheimer’s it is the excessive buildup of the proteins beta-amyloid and tau that leads to brain damage.

Despite evidence of shared disease mechanisms, there is still a large knowledge gap on the pathways that link both neurodegenerative diseases.

To compare similarities and differences between both, researchers from the Emory University School of Medicine identified which proteins are expressed in the brain in each disease.

In a project funded by Accelerating Medicine Partnership, the NINDS Emory Neuroscience Core, the National Institute on Aging, and the Emory Alzheimer’s Disease Research Center, researchers set out to build a comprehensive human brain proteomic data set to be used as a valuable resource for various research endeavors including the identification of disease-specific protein signatures and molecular pathways that are common in Alzheimer’s and Parkinson’s disease.

Brain samples were taken from post-mortem human brain tissues of patients who had either Alzheimer’s or Parkinson’s, and those who had both diseases, as well as healthy controls, across two specific brain regions — the frontal cortex and anterior cingulate gyrus.

Using a method to quantify several brain samples at the same time — with an increased sensitivity to detect proteins usually found at very low levels — researchers identified 11,840 protein groups corresponding to 10,230 genes and covering approximately 65 percent of all the genes expressed in the brain.

This generated a comprehensive and accurate data set where almost all proteins identified — 90 percent — were spotted with high technical confidence. This data set can now be used as a reference for protein expression in the human brain, to compare altered protein levels common to Alzheimer’s and Parkinson’s or specific to each of them; to identify the cellular functions underlying both diseases and provide insights on the clinical status and disease burden; or as a starting point to identify protein modifications associated with these conditions.

The large amount of data collected can advance researchers’ understanding of the underlying mechanisms in neurodegenerative diseases.

“To our knowledge, this is one of the deepest human brain proteomes (whole set of proteins) generated to date. This comprehensive human brain proteomic dataset will serve as a valuable resource for understanding the molecular signatures and pathways that link pathologic mechanisms in both AD and PD,” the researchers said.

https://parkinsonsnewstoday.com/2018/03/20/dataset-parkinsons-brain-advance-knowledge-neurodegenerative-disease-report/

New wearable brain scanner allows patients to move freely for the first time

 March 21, 2018, Wellcome Trust

Brain Scanner. Credit: Wellcome/Nature

A new generation of brain scanner, that can be worn like a helmet allowing patients to move naturally whilst being scanned, has been developed by researchers at the Sir Peter Mansfield Imaging Centre, University of Nottingham and the Wellcome Centre for Human Neuroimaging, UCL. It is part of a five-year Wellcome funded project which has the potential to revolutionise the world of human brain imaging.

n a Nature paper published today (21 March), the researchers demonstrate that they can measure brain activity while people make natural movements, including nodding, stretching, drinking tea and even playing ping pong. Not only can this new, light-weight, magnetoencephalography (MEG) system be worn, but it is also more sensitive than currently available systems.

The researchers hope this new scanner will improve research and treatment for patients who can't use traditional fixed MEG scanners, such as young children with epilepsy or patients with neurodegenerative disorders like Parkinson's disease.

Brain cells operate and communicate by producing electrical currents. These currents generate tiny magnetic fields that are detected outside the head. Researchers use MEG to map brain function by measuring these magnetic fields. This allows for a millisecond-by-millisecond picture of which parts of the brain are engaged when we undertake different tasks, such as speaking or moving.

https://youtu.be/Hx7_SlvWmEs

Current MEG scanners are large and weigh around half a tonne. This is because the sensors used to measure the brain's magnetic field need to be kept very cold (-269°C) which requires bulky cooling technology. With current scanners, the patient must remain very still whilst being scanned, as even a 5-mm movement can make the images unusable. This means it is often difficult to scan people who find it hard to remain still such as young children, or patients with movement disorders. It also poses problems when one might need a patient to remain still for a long time in order to capture a rarely occurring event in the brain, such as an epileptic seizure.

These problems have been solved in the new scanner by scaling down the technology and taking advantage of new 'quantum' sensors that can be mounted in a 3D-printed prototype helmet. As the new sensors are very light in weight and can work at room temperature, they can be placed directly onto the scalp surface. Positioning the sensors much closer to the brain increases the amount of signal that they can pick up.

The light-weight nature of the new scanner also means that, for the first time, subjects can move their heads during the scanning. However, the quantum sensors will only operate in this way when the Earth's magnetic field has been reduced by a factor of around 50,000. To solve this problem, the research team developed special electromagnetic coils, which helped to reduce the Earth's field around the scanner. These coils were designed specifically to sit either side of the subject, and close to the walls of the room, to ensure that the scanner environment is not claustrophobic.

The scanner is based around helmets that can be made to fit anyone who needs to be scanned. Following success of their prototype system, the researchers are now working towards new styles of helmet, which will have the appearance of a bicycle helmet, that will be suitable for babies and children as well as adults. The researchers predict this new type of scanner will provide a four-fold increase in sensitivity in adults, potentially increasing to 15 or 20-fold with infants.

Professor Gareth Barnes, who leads the project at the Wellcome Trust Centre for Human Neuroimaging at UCL, said: "This has the potential to revolutionise the brain imaging field, and transform the scientific and clinical questions that can be addressed with human brain imaging. Our scanner can be worn on the head like a helmet, meaning people can undertake tasks whilst moving freely. Importantly, we will now be able to study brain function in many people who, up until now, have been extremely difficult to scan - including young children and patients with movement disorders. This will help us better understand healthy brain development in children, as well as the management of neurological and mental health disorders"

Dr Matt Brookes who leads the MEG work in Nottingham, where the prototype was built, said: "This new technology raises exciting new opportunities for a new generation of functional brain imaging. Being able to scan individuals whilst they move around offers new possibilities, for example to measure brain function during real world tasks, or genuine social interactions. This has significant potential for impact on our understanding of not only healthy brain function but also on a range of neurological, neurodegenerative and mental health conditions."

Professor Richard Bowtell, Director of the Sir Peter Mansfield Imaging Centre in Nottingham added "It's great to see this collaboration between neuroscientists, engineers and physicists from two different universities producing a potential step-change in brain scanning technology. This was made possible by a Wellcome Collaborative Award which is an important funding stream that aims to promote the development of new ideas and speed the pace of discovery"

Andrew Welchman, Wellcome's Head of Neuroscience and Mental Health, said: "MEG is a really valuable tool in neuroscience, but current scanners are still not widely used as they're expensive, cumbersome and their 'one-size-fits-all' design doesn't work for many patients. This new scanner is exciting not only because it overcomes those issues and will help improve our understanding of how the brain works but also because it has huge potential for clinical use. This could lead to better care for patients, such as young children and people with epilepsy where current options are severely limited and very invasive."

More information: Moving magnetoencephalography towards real-world applications with a wearable system, Nature (2018). nature.com/articles/doi:10.1038/nature26147 

Journal reference: Nature  

Provided by: Wellcome Trust

https://medicalxpress.com/news/2018-03-wearable-brain-scanner-patients-freely.html

Neuroscientists develop potential tools for the study of brain function

 March 21, 2018 by Jeff Sossamon, University of Missouri-Columbia

Lorin Milescu, Troy Zars, and Mirela Milescu led a team that characterized the new thermogenetic tool. Credit: Melody Kroll, MU Division of Biological Sciences

A team of University of Missouri neuroscientists are inching closer to developing the tools needed to decipher the brain. In 2015, the team received a National Science Foundation Early Concept Grant for Exploratory Research (EAGER) award to investigate a newly discovered class of proteins that are turned on by heat. Now, the team has published a new paper that demonstrates how these proteins can be used as tools to regulate the activity of individual neurons in the brain through changes in temperature. These tools will advance fundamental brain research and potentially lead to "deep brain stimulation" treatments used for Alzheimer's and Parkinson's patients.

Thermogenetic tools, which utilize heat to act as a 'switch' to turn neuron functions on, are expanding the horizons of brain research by allowing us to control specific neurons in the brain and measure behavioral changes," said Troy Zars, professor of biological sciences in the MU College of Arts and Science. "The goal of this fundamental research was to identify more of these special proteins, laying the foundation so that, in the future, scientists have a better understanding of how neuronal circuits function."

The research team was led by Zars, as well as Mirela Milescu and Lorin Milescu, who both are assistant professors of biological sciences at MU. The team included four undergraduate and four graduate students. Together, the researchers focused on a family of genes that encode taste receptors found in fruit flies. Surprisingly, some of these taste receptors also are activated by heat and thus play a role in detecting environmental temperature.

First, the students in Mirela Milescu's lab investigated the thermosensitivity of these proteins and identified one member of the family, called Gr28bD, as a prime candidate for thermogenetics. Then, Lorin Milescu's students used live-imaging techniques and software developed in their lab to demonstrate that the Gr28bD protein can, through temperature differences, modulate the brain activity of fruit flies.

Finally, the flies were tested in Dr. Troy Zars' lab for temperature-dependent behavior. Using a specially designed heat chamber that allows precise control of the environmental temperature, the Zars' students were able to show that the Gr28bD protein can control behavior in these flies, using temperature as a "brain switch."

"Gr28bD could become a powerful tool in controlling neuronal activity and studying how neuronal circuits function," said Benton Berigan, a graduate student in Lorin Milescu's lab. "Since this protein is not found in any mammal, it emerges as a good candidate for the development of novel thermogenetic tools to be used for basic research and potentially one day in humans."

Further study of thermogenetics could lead to the development of deep brain stimulation tools as a part of the national Brain Research through Advancing Innovative Neurotechnologies (BRAIN) project, Zars said.

This research highlights the power of translational precision medicine and the promise of the proposed Translational Precision Medicine Complex (TPMC) at the University of Missouri. The TPMC will bring together industry partners, multiple schools and colleges on campus, and the federal and state government to enable precision and personalized medicine. Scientific advancements made at MU will be effectively translated into new drugs, devices and treatments that deliver customized patient care based on an individual's genes, environment and lifestyle, ultimately improving health and well-being of people.

The study, "The Drosophila Gr28bD product is a non-specific cation channel that can be used as a novel thermogenetic tool," recently was published in Scientific Reports.

More information: Aditi Mishra et al, The Drosophila Gr28bD product is a non-specific cation channel that can be used as a novel thermogenetic tool, Scientific Reports (2018).  DOI: 10.1038/s41598-017-19065-4 

Journal reference: Scientific Reports

Provided by: University of Missouri-Columbia 

https://medicalxpress.com/news/2018-03-neuroscientists-potential-tools-brain-function.html

Systems approaches to optimizing deep brain stimulation therapies in Parkinson's disease

March 21, 2018, Wiley

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

Systems biologists, physicists, and engineers have intensively worked at computational tools to analyze, predict, and optimize the effects of Deep Brain Stimulation (DBS) to treat chronic neurological diseases. These efforts often have overlapping objectives and closely-related methods, but they are rarely compared, combined, or jointly discussed, perhaps because they often target different research communities.

A new WIREs Systems Biology and Medicine review systematically brings this information together to identify the major milestones in the development of systems approaches to the modeling and study of Parkinson's disease and DBS. These approaches acknowledge the interactive nature and interdependence of various factors to optimize the therapeutic effects of DBS in individual patients.

"Although effective and generally safe, DBS remains a fascinating puzzle to scientists, physicians, and engineers. The therapeutic mechanisms of DBS, in fact, are still elusive and the current, semi-permanent stimulation protocols have often motivated the investigation of ways to make DBS less invasive and more efficient," said lead author Dr. Sabato Santaniello, of the University of Connecticut. "In this review article, we show how different strides in medical imaging, computer modeling, and control strategies have paved the way towards a truly patient-specific optimization of DBS therapy.

More information: Sabato Santaniello et al, Systems approaches to optimizing deep brain stimulation therapies in Parkinson's disease, Wiley Interdisciplinary Reviews: Systems Biology and Medicine (2018).  DOI: 10.1002/wsbm.1421 

Provided by: Wiley 

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