Scientists May Have Found Link Between Gut Bacteria and Parkinson’s

December 4, 2016

A new study shows that certain types of bacteria in the intestines might be linked to the development of Parkinson’s disease (PD) and paves the way for future research and treatment.

New research in this direction could reveal the impact of gut microbiota on the central nervous system and neurological diseases. "Although neurological diseases have been historically studied within the CNS [central nervous system], peripheral influences have been implicated in the onset and/or progression of diseases that impact the brain," the scientists wrote in the article, published December 1 in the journal Cell. "Research into how the gut-brain axis influences neurological conditions may reveal insights into disease etiology." Tests were done on two groups of mice, with one raised in normal, germy conditions, the other in a completely sterile environment. Mice raised in germy conditions developed Parkinson's symptoms.Then the mice were given germs. "When we transferred microbiota from Parkinson's disease patients, the mice developed more severe symptoms than when they got microbiota from healthy controls," Sarkis Mazmanian said, according to NBC News.

"Remarkably, fecal microbes from PD patients impair motor function significantly more than microbiota from healthy controls when transplanted into mice. Together, these results suggest that gut microbes may play a critical and functional role in the pathogenesis of synucleinopathies [diseases that include multiple system atrophy, and Lewy body disease] such as PD." But the researchers caution against drawing hasty conclusions, as the experiments have not been done on people. The link between neurodegenerative diseases and gut bacteria is not proven. Science does not yet know all different species of bacteria living in the intestines, let alone those that affect Parkinson's. "I am sure sensational claims will be made," Mazmanian said. "I have seen people misrepresent our research. 

This research opens doors but it doesn't mean that we have solved the problem of Parkinson's disease." "It's mouse research and doesn't mean we've done anything yet to help people." Mazmanian suggests that if the link between the bacteria and disease is proven, then the treatment could be made more efficient by getting drugs into the gut instead of the brain. "I think it is going to be one of these groundbreaking pieces of research," said James Beck, vice president for scientific affairs at the Parkinson's Disease Foundation, which was not involved in the research, according to NBC News. "It might lead to new therapies." In 2014, researchers at Arizona State University reported results of a similar experiment that posited gut bacteria's role in the development of autism. Many more years are needed to prove the relation between the two, however.

https://sputniknews.com/art_living/201612041048138964-gut-bacteria-parkinsons/

Standing Up May Unmask Cognitive Deficits in Patients With Parkinson’s

NEUROSCIENCE NEWSDECEMBER 3, 2016

Summary: According to researchers, Parkinson’s patients who have a drop in blood pressure when standing exhibit significant cognitive deficits. 

Source: BIDMC.

In a previous study, Freeman and colleagues demonstrated that orthostatic hypotension is linked to reversible cognitive impairment in patients with a rare neurological disorder called autoimmune autonomic ganglionopathy. In this new study of the far more prevalent Parkinson’s disease, the researchers investigated whether OH is linked to reversible cognitive deficits in patients with PD as well. NeuroscienceNews.com image is in the public domain.

Posture-mediated low blood pressure could serve as a target for intervention.

In a new study published online today in the journal Neurology, a research team led by neurologists at Beth Israel Deaconess Medical Center (BIDMC) and neuropsychologists at Boston University has shown that when patients with Parkinson’s disease experience a drop in blood pressure upon standing up – a condition known as orthostatic hypotension (OH) – they exhibit significant cognitive deficits. These deficits reverse when they lie down and their blood pressure returns to normal.

These cognitive impairments may go unnoticed by physicians assessing patients with Parkinson’s who are lying down or seated, and could lead to difficulty in daily activities performed while standing and walking, such as tracking conversations, counting change and interpreting traffic signals.

“Cognitive impairment is a common symptom of Parkinson’s disease,” said co-senior author Roy Freeman, MD, director of the Center for Autonomic and Peripheral Nerve Disorders at BIDMC and a professor of neurology at Harvard Medical School (HMS). “In this study, we demonstrated that the upright posture in patients with Parkinson’s disease exacerbated cognitive deficits, and that this effect is transient and reversible. Based on these results, we encourage clinicians to include cognitive testing in a variety of postures in their assessments of patients.”

Marked by characteristic tremor, rigidity and slowness of movement, Parkinson’s disease (PD) is a progressive degeneration of parts of the nervous system. It affects many aspects of movement and can cause a masklike, expressionless face, rigid limbs, and problems with walking and posture. PD is also associated with cognitive defects attributed to breakdowns in connectivity between regions of the brain. Up to 50 percent of people with Parkinson’s disease may also have orthostatic hypotension.

In a previous study, Freeman and colleagues demonstrated that orthostatic hypotension is linked to reversible cognitive impairment in patients with a rare neurological disorder called autoimmune autonomic ganglionopathy. In this new study of the far more prevalent Parkinson’s disease, the researchers investigated whether OH is linked to reversible cognitive deficits in patients with PD as well.

Freeman and colleagues including lead author Justin Centi and co-senior author Alice Cronin-Golomb, PhD, director of the Vision and Cognition Laboratory and Center for Clinical Biopsychology and a professor of psychological and brain sciences at Boston University, divided 55 volunteers into three study groups: 18 patients with both PD and OH, 19 patients with PD but without OH, and 18 control participants with neither PD nor OH. All participants were given a series of cognitive tests, with the tests administered while supine and again while tilted to 60 degrees. Researchers measured and recorded the participants’ blood pressure before and during each round of cognitive testing to ensure that participants were never at risk for fainting.

“As we suspected, people with both Parkinson’s disease and orthostatic hypotension showed posture-related impairments when upright relative to supine on nearly all measures of cognition,” said Centi, who noted that study participants with Parkinson’s disease without orthostatic hypotension demonstrated deficits on only two cognitive tests. There was no difference between upright and supine scores for the control group.

When the three groups’ relative performances were compared to each other, postural changes had no significant impact on participants with PD but without OH, compared to the control group. However, Participants with PD and OH were far more susceptible to posture-related impairment on several tests, including those that measured math skills, the ability to produce words easily, keeping information in mind while working on it, paying sufficient attention so that later memory is efficient and searching for items quickly and accurately.

Essentially all neuropsychological tests are given to patients in the seated position in the clinic as well as during most research studies – with the exception of imaging studies in which the patient is lying down,” said Cronin-Golomb. “The cognitive performance that we see in those patients with Parkinson’s disease who are tested when seated or lying down in fact may underestimate their cognitive problems in real life, when they are standing up and going about their business of daily activities. Also, the patterns of brain activity that we see on imaging when they are lying down may not be the patterns that the brain produces during normal upright activity.”

Cognitive deficits in PD result, at least in part, from neurodegeneration, the authors explained. But transient blood pressure changes when upright may indeed play a contributing role. Clinical providers might miss an important target for intervention when not considering OH as a contributor to cognitive impairment.

ABOUT THIS PARKINSON’S DISEASE RESEARCH ARTICLE

In addition to Freeman, Centi, and Cronin-Golomb, study coauthors included Christopher H. Gibbons, MD, of BIDMC and HMS; Sandy Neargarder, PhD, of Boston University and Bridgewater State University; and Alex Canova of Boston University.

Funding: This work was funded by grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke (R01NS067128) and support from a Ruth L. Kirschstein National Research Service Award (F31NS074801).

Source: Jacqueline Mitchell – BIDMC 

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Abstract for “Effects of orthostatic hypotension on cognition in Parkinson disease” by Justin Centi, Roy Freeman, Christopher H. Gibbons, Sandy Neargarder, Alexander O. Canova, and Alice Cronin-Golomb in Neurology. Published online November 30 2016 doi:10.1212/WNL.0000000000003452

Abstract

Effects of orthostatic hypotension on cognition in Parkinson disease

Objective: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in Parkinson disease (PD) using a cross-sectional and within-group design.

Methods: Individuals without dementia with idiopathic PD included 18 with OH (PDOH) and 19 without OH; 18 control participants were also included. Neuropsychological tests were conducted in supine and upright-tilted positions. Blood pressure was assessed in each posture.

Results: The PD groups performed similarly while supine, demonstrating executive dysfunction in sustained attention and response inhibition, and reduced semantic fluency and verbal memory (encoding and retention). Upright posture exacerbated and broadened these deficits in the PDOH group to include phonemic fluency, psychomotor speed, and auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, with the PDOH group exhibiting a wider range of deficits in executive function and memory as well as significant changes in visuospatial function.

Conclusions: Cognitive deficits in PD have been widely reported with assessments performed in the supine position, as seen in both our PD groups. Here we demonstrated that those with PDOH had transient, posture-mediated changes in excess of those found in PD without OH. These observed changes suggest an acute, reversible effect. Understanding the effects of OH due to autonomic failure on cognition is desirable, particularly as neuroimaging and clinical assessments collect data only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with OH has quality of life implications, and OH presents itself as a possible target for intervention in cognitive disturbance.

“Effects of orthostatic hypotension on cognition in Parkinson disease” by Justin Centi, Roy Freeman, Christopher H. Gibbons, Sandy Neargarder, Alexander O. Canova, and Alice Cronin-Golomb in Neurology. Published online November 30 2016 doi:10.1212/WNL.0000000000003452

http://neurosciencenews.com/parkinsons-blood-pressure-5670/

Being Part of a Community Group May Protect You From Cognitive Decline

NEUROSCIENCE NEWSDECEMBER 3, 2016

Summary: Researchers report people aged 50 and over who participate in social activity through a community based group appear to have better cognitive function than their less social peers.

Source: Biomed Central.

Previous research has suggested that social integration, social engagement and strong social networks may be associated with better cognitive outcomes. Neurosciencenews image is for illustrative purposes only.

Social engagement through civic group activities, such as being a member of a political party, an environmental group, neighborhood watch, a voluntary service group or other community based groups, is associated with better cognitive function at age 50, according to a study published in the open access journal BMC Psychology which included 9,119 men and women from England, Scotland and Wales.

Researchers at the University of Southampton found that a person’s cognitive ability at age 11; their participation in civic activities at ages 33 and 50; frequent physical activity; higher educational qualification and female gender were all associated with better cognitive function at age 50. Having low socio-economic status as a child and reporting worse mental well-being in adulthood were both associated with worse cognitive function at age 50.

Professor Ann Bowling, lead author of the study said: “While the associations between adult social engagement and cognitive function at age 50 we found were moderate, they persisted after we adjusted for covariates, such as health, socio-economic status and gender. The implication is that if people continue to engage socially throughout life, maintaining related behaviours that require cognitive skills such as memory, attention and control, there may be some protection from cognitive decline. Public health policy interventions aimed at promoting cognitive health could include encouraging civic engagement and providing people with opportunities for this.”

Previous research has suggested that social integration, social engagement and strong social networks may be associated with better cognitive outcomes. Furthermore, social capital – opportunities within communities for social, leisure, recreational activities, voluntary work or group membership – have been shown to be associated with enhanced well-being and better reported mental health, as well as reduced levels of stress, loneliness and isolation. However, few of these studies followed participants throughout their life.

To investigate associations between people’s social engagement throughout their adult life and cognitive function at age 50, the researchers used data from the British National Child Development Study (NCDS), a general population sample in England, Scotland and Wales. Baseline data was collected at birth in 1958 and study participants were followed up at several points later in life.

At age 33, 83% of all respondents reported that they did not participate in any civic organization. This number dropped to 64% at age 50. Participating in one civic organization was reported by 14% of respondents at age 33 and by 25% at age 50. Out of the overall sample, 8,129 participants completed cognitive tests at ages eleven (reading, writing, math, and general ability tests) and 50 (memory and visual attention, speed and concentration tests). The researchers found that almost a third of the sample population’s cognitive ability deteriorated between ages eleven and 50, while remaining unchanged in less than half of participants (44%). A quarter of participants showed improved cognitive ability at age 50. Those who reported that they participated in civic groups at age 33 and 50 scored higher in cognitive tests. Also, participation in each additional civic group was found to further increase scores on cognitive tests.

The present study used a large, longitudinal cohort with strong initial response rates, allowing the researchers to take into account complex interactions between social and biological processes and to adjust for various confounding factors. However, observational studies like this one cannot show cause and effect, but can describe possible links.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Anne Korn – Biomed Central

Image Source: This NeuroscienceNews.com image is in the public domain.

Original Research: Full open access research for “Is mid-life social participation associated with cognitive function at age 50? Results from the British National Child Development Study (NCDS)” by Ann Bowling, Jitka Pikhartova and Brian Dodgeon in BMC Psychology. Published online December 2 2016 doi:10.1186/s40359-016-0164-x

Abstract

Is mid-life social participation associated with cognitive function at age 50? Results from the British National Child Development Study (NCDS)

Background

Some studies have indicated that social engagement is associated with better cognitive outcomes. This study aimed to investigate associations between life-course social engagement (civic participation) and cognitive status at age 50, adjusting for social networks and support, behavioural, health, social and socio-economic characteristics.

Methods

The vehicle for the study was the National Child Development Study (1958 Birth Cohort Study), which is a general population sample in England, Scotland and Wales (9119: 4497 men and 4622 women) participating in nationally representative, prospective birth cohort surveys. The primary outcome variable was cognitive status at age 50, measured by memory test (immediate and delayed word recall test) and executive functioning test (word fluency and letter cancelation tests). The influence of hypothesised predictor variables was analysed using linear multiple regression analysis.

Results

Cognitive ability at age 11 (β = 0.19;95% CI = 0.17 to 0.21), participation in civic activities at ages 33 (0.12; 0.02 to 0.22) and 50 (0.13; 0.07 to 0.20), frequent engagement in physical activity (sport) (β from 0.15 to 0.18), achieving higher level qualifications (β from 0.23 to 1.08), and female gender (β = 0.49;95% CI = 0.38 to 0.60) were positively, significantly and independently associated with cognitive status at age 50. Having low socio-economic status at ages 11 (β from -0.22 to -0.27) and 42 (β from -0.28 to -0.38), and manifesting worse mental well-being at age 42 (β = -0.18; 95% CI = -0.33 to -0.02) were inversely associated with cognitive status at age 50. The proportion of explained variance in the multiple regression model (18%), while modest, is impressive given the multi-faceted causal nature of cognitive status.

Conclusions

The results indicate that modest associations between adult social engagement and cognitive function at age 50 persist after adjusting for covariates which included health, socio-economic status and gender, supporting theories of neuroplasticity. In addition to the continuing emphasis on physical activity, the encouragement of civic participation, at least as early as mid-life, should be a targeted policy to potentially promote and protect cognitive function in later mid-life.

“Is mid-life social participation associated with cognitive function at age 50? Results from the British National Child Development Study (NCDS)” by Ann Bowling, Jitka Pikhartova and Brian Dodgeon in BMC Psychology. Published online December 2 2016 doi:10.1186/s40359-016-0164-x

http://neurosciencenews.com/cognitive-decline-social-group-5668/

Parkinson’s ‘fool’ conjures up music, magic, motivation

 December 1, 2016 by patricia corrigan , j. correspondent

Richard Horn doesn’t let Parkinson’s stop him from playing piano.

Card tricks, piano riffs and insights into how the brain works. These all are part of “The Brain, the Mind, Magic and Music,” an unusual program coming soon to a Bay Area JCC near you.

Richard Horn’s 90-minute show, subtitled “Making a Fool out of Parkinson’s Disease,” is part entertainment, part motivational speech about aging and part his plucky response to coping with a disease.

Horn, 71, is a magician, a musician and an authority on how the brain produces consciousness. In 2010, shortly after retiring as a researcher and teacher from Thomas Jefferson University in Philadelphia, Horn was diagnosed with Parkinson’s disease.

“I’ve continued to do things that Parkinson’s disease eventually will steal from me, and I have learned that many people can still use their bodies and minds effectively when dealing with a cloud hanging over them like this medical diagnosis,” Horn said recently from his home in Philadelphia. “That is why I do this show.”

Horn will present “The Brain, the Mind, Magic and Music” Dec. 11 at the Peninsula JCC in Foster City, Dec. 12 at the Osher Marin JCC in San Rafael and Dec. 13 at the Oshman Family JCC in Palo Alto. SV Productions in Sunnyvale, which specializes in booking Israeli shows and concerts, is presenting Horn’s show.

Danielle Vierra of the Osher Marin JCC said she is looking forward to what she called Horn’s “upbeat perspective” on aging.

“We are prioritizing engaging our older adult community, trying to encourage them to take in as much information as they can about how to age in a healthy way,” said Vierra, the program supervisor for the Kurland Center for Adult Learning and Living at the JCC in San Rafael. “Dr. Horn presents a vibrant way of confronting aging.”

Horn grew up in Syracuse, New York. His father was an Ashkenazi Jew born in Germany and his mother was a Sephardic Jew born in the United States. “We attended a Reform temple when I was growing up, and though I did get bar mitzvah, we weren’t that active as practicing Jews,” he said.

So which came first: the magic, the music or Horn’s academic career?

“I started playing piano when I was 7, and I’ve never stopped,” said Horn, who was a full-fledged professional in the ’70s who said he played with the likes of B.B. King, Helen Reddy, and Gladys Knight and the Pips. “I’m a performer by nature. That’s something my parents encouraged me to do.”

But Horn has always had multiple talents, or at least sought to learn and master them, from counting cards in Las Vegas to being asked to perform magic tricks at his brother-in-law’s 60th birthday party a decade ago.

“I got hooked,” he said of learning magic. “Later, I bought card tricks” and then learned how to do card manipulations with a regular deck.

From there, things took off. He went on to receive an award for close-up magic from a chapter of the International Brotherhood of Magicians, and he currently performs magic at corporate events, parties and wedding receptions.

In “The Brain, the Mind, Magic and Music,” Horn showcases some of what he has learned and still loves, though his illness does present some challenges.

“The more you challenge the affected limbs with movement, the better you can control the symptoms, but my facial expression now has a flat effect, and people tell me I look bored,” he said.

“I’m not bored at all.”

“The Brain, the Mind, Magic and Music.” 10 a.m. Dec. 11 at Peninsula JCC, Foster City; 1 p.m. Dec. 12 at Osher Marin JCC, San Rafael; 1 p.m. Dec. 13 at Oshman Family JCC, Palo Alto. For cost and other details, contact appropriate JCC or visit http://www.tinyurl.com/brain-horn.

http://www.jweekly.com/article/full/79048/parkinsons-fool-conjures-up-music-magic-motivation/

Social-Media Hype about Diseases and Treatments Does Patients No Favors

• By Israel Robledo on December 2, 2016

A downside to the awesome power of these platforms comes from not knowing or perhaps not caring about the source of information

As has often been said, with great power comes great responsibility. As we saw in the recent election, social media is a great example of a powerful medium that can change minds and change lives but can also give credibility to false or misguiding information.

As someone diagnosed with Parkinson’s disease (PD) nine years ago, I’ve thrilled at seeing social media’s growing power as an agent for good. As our advocacy community has grown, social media has allowed for more information to be circulated in the PD community than ever before, and has become a vital link through which we share experiences, raise awareness about quality of life issues, point people to clinical trials, spread knowledge about cutting-edge research—and importantly, raise critical dollars to fund it. Connecting our community more tightly together has underscored the important role each of us can play in finding an eventual cure.

A downside to the awesome power of this platform comes from not knowing or perhaps not caring about the source of information shared on social media. Just as “fake news” has flourished in an environment where speed, rather than accuracy, is what counts, patients—who are understandably vulnerable to hopeful reports about their disease—must recognize that not everything they read is equally credible.  In my years of advocating for PD-related causes, hundreds of so-called “miracles” have been announced, all of which have proven to have disappointing results.

Recently there was a flurry of media coverage and excitement in the patient community about a small, open-label study in which people with PD were given a cancer drug called nilotinib. The majority reported major improvement in their PD symptoms. Recognizing a good story, highly respected media outlets including NPR featured hopeful accounts of patients who saw nilotinib as a miracle drug. Social media channels lit up with the news, causing many in the PD community to ask their physicians to prescribe it without knowing whether the drug would be safe or effective for long-term use in PD. One comment that caught my attention on social media: “I don’t understand what the problem is. It works. Give it to everybody with PD.

Somehow, lost in all the hype was the fact that the study only included 11 people with PD given nilotinib for 6 months (one of the 12 patients died during the study)—not a scientifically valid sample size nor study design. Also lost in translation was the fact that nilotinib, when used in cancer, carries a black-box warning regarding life-threatening risks associated with the drug. As someone with no scientific background but keen interest in research, I wouldn’t have given these results a second look. Instead, I was frustrated and saddened to learn that so many people had pinned their hopes on such flimsy research.

Sound, responsible science needs to be held to the highest standards, and I wish that more attention had been paid to the study’s early stage; if so, I believe the response would have been more measured. There is a purpose and a reason that protocols for human research have developed, and that is to balance the need to move as quickly as possible toward effective treatments against the need to ensure the safety of everyone who takes a drug.

The research community is working on behalf of all of us, and we owe them our gratitude. Nonetheless, scientists must be vigilant in their commitment to present promising early information only alongside a full accounting of possible risk.

As patients, we fervently wish that finding the “miracle cure” were easy. But in our heart of hearts, we know there is much more involved in finding out if a treatment is effective in slowing or stopping the progression of a disease. We, too, have a responsibility to educate ourselves, ask the tough questions, and balance the hype even as we allow ourselves cautious optimism about possible steps forward.

The PD community has accomplished so much: we are close to unraveling the underlying mechanisms of the cellular process of PD, and to vastly improved solutions for diagnosing, treating and managing the disease. Breakthroughs are sure to come if we keep invested in the process; we each have an important part to play. Nevertheless, our inability to date in finding a cure leaves us vulnerable, not just in our bodies, but also in false hope.

I ask the PD community—including family and friends—that we take a more tempered approach to what we read and with what standards we judge, especially in the online world. Our need is great, and our responsibility is greater. To the media and the grassroots social media community, please, dig deeper and make sure what you promote is the real deal. We want to believe you.

https://blogs.scientificamerican.com/guest-blog/social-media-hype-about-diseases-and-treatments-does-patients-no-favors/

A Radiation-Free Approach to Imaging Molecules in the Brain

NEUROSCIENCE NEWSDECEMBER 2, 2016

Summary: Researchers have developed a new probe that can induce blood flow changes that allows for neuroimaging without the use of radioactive labels.

Source: MIT.

Scientists hoping to see molecules that control brain activity have devised a probe that lets them image such molecules without using chemical or radioactive labels. The sensors consist of proteins that detect a particular target, which causes them to dilate blood vessels, producing a change in blood flow that can be imaged with magnetic resonance imaging (MRI) or other techniques. Neurosciencenews image is credited to the researchers.

New probe induces blood flow changes that can be seen by MRI.

Scientists hoping to get a glimpse of molecules that control brain activity have devised a new probe that allows them to image these molecules without using any chemical or radioactive labels.

Currently the gold standard approach to imaging molecules in the brain is to tag them with radioactive probes. However, these probes offer low resolution and they can’t easily be used to watch dynamic events, says Alan Jasanoff, an MIT professor of biological engineering.

Jasanoff and his colleagues have developed new sensors consisting of proteins designed to detect a particular target, which causes them to dilate blood vessels in the immediate area. This produces a change in blood flow that can be imaged with magnetic resonance imaging (MRI) or other imaging techniques.

“This is an idea that enables us to detect molecules that are in the brain at biologically low levels, and to do that with these imaging agents or contrast agents that can ultimately be used in humans,” Jasanoff says. “We can also turn them on and off, and that’s really key to trying to detect dynamic processes in the brain.”

In a paper appearing in the December 2 issue of Nature Communications, Jasanoff and his colleagues used these probes to detect enzymes called proteases, but their ultimate goal is to use them to monitor the activity of neurotransmitters, which act as chemical messengers between brain cells.

The paper’s lead authors are postdoc Mitul Desai and former MIT graduate student Adrian Slusarczyk. Recent MIT graduate Ashley Chapin and postdoc Mariya Barch are also authors of the paper.

Indirect imaging

To make their probes, the researchers modified a naturally occurring peptide called calcitonin gene-related peptide (CGRP), which is active primarily during migraines or inflammation. The researchers engineered the peptides so that they are trapped within a protein cage that keeps them from interacting with blood vessels. When the peptides encounter proteases in the brain, the proteases cut the cages open and the CGRP causes nearby blood vessels to dilate. Imaging this dilation with MRI allows the researchers to determine where the proteases were detected.

“These are molecules that aren’t visualized directly, but instead produce changes in the body that can then be visualized very effectively by imaging,” Jasanoff says.

Proteases are sometimes used as biomarkers to diagnose diseases such as cancer and Alzheimer’s disease. However, Jasanoff’s lab used them in this study mainly to demonstrate the validity their approach. Now, they are working on adapting these imaging agents to monitor neurotransmitters, such as dopamine and serotonin, that are critical to cognition and processing emotions.

To do that, the researchers plan to modify the cages surrounding the CGRP so that they can be removed by interaction with a particular neurotransmitter.

“What we want to be able to do is detect levels of neurotransmitter that are 100-fold lower than what we’ve seen so far. We also want to be able to use far less of these molecular imaging agents in organisms. That’s one of the key hurdles to trying to bring this approach into people,” Jasanoff says.

Tracking genes

Another possible application for this type of imaging is to engineer cells so that the gene for CGRP is turned on at the same time that a gene of interest is turned on. That way, scientists could use the CGRP-induced changes in blood flow to track which cells are expressing the target gene, which could help them determine the roles of those cells and genes in different behaviors. Jasanoff’s team demonstrated the feasibility of this approach by showing that implanted cells expressing CGRP could be recognized by imaging.

“Many behaviors involve turning on genes, and you could use this kind of approach to measure where and when the genes are turned on in different parts of the brain,” Jasanoff says.

His lab is also working on ways to deliver the peptides without injecting them, which would require finding a way to get them to pass through the blood-brain barrier. This barrier separates the brain from circulating blood and prevents large molecules from entering the brain.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: The research was funded by the National Institutes of Health BRAIN Initiative and the MIT Simons Center for the Social Brain.

Source: Sarah McDonnell – MIT

Image Source: NeuroscienceNews.com image is credited to the researchers.

Original Research: Full open access research for “Molecular imaging with engineered physiology” by Mitul Desai, Adrian L. Slusarczyk, Ashley Chapin, Mariya Barch & Alan Jasanoff in Nature Communications. Published online December 2 2026 doi:10.1038/ncomms13607

Abstract

Molecular imaging with engineered physiology

In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms.

“Molecular imaging with engineered physiology” by Mitul Desai, Adrian L. Slusarczyk, Ashley Chapin, Mariya Barch & Alan Jasanoff in Nature Communications. Published online December 2 2026 doi:10.1038/ncomms13607

http://neurosciencenews.com/radiation-free-neuroimaging-5659/

Deep Brain Stimulation: Indications and Applications

December 2, 2016

By ZeeshanHashmi

MIRPURKHAS: An estimated 400,000 people in Pakistan are suffering from the Parkinson's disease, which affects over 6 million persons globally.

This was disclosed by neurosurgeon and Assistant Professor, Department of Neurosurgery at Muhammad Medical Hospital Mirpurkhas, Dr Fayaaz Memon in an interview with the Daily Times.

Expressing grave concern over the increasing number of patients with Parkinson's disease in Pakistan, he said though the disease can affect anyone, it usually emerges in people over the age of 60 and such patients need moral and socio-economic support from the family members particularly and the society as whole. The diagnosis was based on patient's medical history and a methodical neurological examination as the symptoms of the disease can be caused by other neurological problems as well, said Dr Fayaaz Memon.

He said that the Parkinson's was a chronic debilitating disease, which directly affects muscle reflexes, body movements and can severely impact a patient's vision. Globally, there are over six million people who are suffering from the disease, he said adding that though tests such as MRI and CT scans were useful, but are not essential for the diagnosis and the disease has many symptoms with the most common including tremors, stiffness and rigidity, imbalance and slow movement.

Dr Memon said that the Parkinson's patients should also look out for eye problems as they suffer higher incidence of certain eye problems, particularly those related to difficulty in focusing, following or tracking objects, double vision, dry eyes and eyelid infections.

Dr Fayaaz Memon further informed that people with Parkinson's disease usually suffer from movement problems and physiotherapy plays a significant role in managing the disease and helps people to continue with daily routine activities independently.

He further said that it leads to a number of problems, such as difficulty in speaking, slow pace of walking, and problems in swallowing. However, with the right combination of medication, physical exercise and therapy, people affected by Parkinson's disease can live a healthy life, he remarked.

Most of the time, elderly people were victims of this disease, and in Pakistan, there is a need to create public awareness about the disease on a massive scale to diagnose and cure Parkinson's.

Dr Fayaaz Memon elaborated on the respiratory complications which appear due to Parkinson's and informed that those include possible infections in the vocal cord, high probability of developing pneumonia, as well as long periods of fatigue. He urged patients to strictly abide by the prescribed medication and exercise regularly as described by the doctor.

He said that encouragement of Parkinson patient was crucial along with treatment as willpower could play a vital role in recovery process.

Dr Fayaaz Memon said that a revolution has come into the medical science and now treatment and cure of this disease was possible through surgery and medicine. He stressed that there were treatment available that can relieve the symptoms or slow the progress but the commitment to live a better life must come from the patient.

http://dailytimes.com.pk/sindh/02-Dec-16/400000-people-suffering-from-parkinsons-disease

NeuroDerm Announces Top-Line Results of Pilot PK Trial Comparing ND0701 with Commercial Apomorphine

DECEMBER 2, 2016

Regulatory Development of ND0701 in the EU to Proceed Based on PK Similarity for the Treatment of Parkinson’s Disease

REHOVOT, Israel, Dec. 02, 2016 (GLOBE NEWSWIRE) -- NeuroDerm Ltd. (Nasdaq:NDRM), a clinical stage pharmaceutical Company developing drugs for central nervous system (CNS) disorders, today announced the completion of a pilot study (trial 101) in healthy subjects comparing the pharmacokinetics (PK) of ND0701, the Company’s proprietary continuous, subcutaneously delivered apomorphine liquid formulation, and commercial apomorphine (APOGO^®). Study results demonstrate that ND0701 produced PK results that were comparable to those produced by the referenced drug.  Based on these results, the Company plans to pursue a PK similarity regulatory development route in the EU for ND0701, will initiate a follow-up comparison PK study in the first half of 2017 and meet with European regulatory authorities in the second half of 2017 to discuss its development strategy.  The Company is evaluating in parallel the development of ND0701 for the U.S. market.

Trial 101 Design
Trial 101 was a pilot crossover, randomized, two-sequence, 12-hour study with 18 healthy volunteers.  The primary objective was to evaluate the PK and relative bioavailability of sub-cutaneous infusion of ND0701 and commercial apomorphine.  No formal power analysis was performed for this study.

Trial 101 Results
Plasma PK measures of ND0701 were comparable to the reference drug. These results support the continuation of ND0701’s development path to demonstrate its therapeutic equivalence to the reference drug.  ND0701 did not raise safety and tolerability concerns, and exhibited a slightly better safety profile than that of the reference drug.

“We are pleased that trial 101 yielded positive results,” said Oded S. Lieberman, PhD, CEO of NeuroDerm.  “The PK profile of ND0701 supports its continued development as a potentially important new, continuous dopaminergic treatment alternative for advanced Parkinson’s patients, designed for eventual administration through a patch pump.  Data from this pilot study will enable us to optimize the design of the upcoming study, and to proceed with a PK similarity regulatory development in the EU.”

About ND0701
ND0701 contains apomorphine, the most potent dopamine agonist. Apomorphine, administered subcutaneously, is the most effective drug for the symptomatic treatment of Parkinson's disease after levodopa. Apomorphine is approved both in the United States and in the EU for acute administration as rescue treatment for off periods in Parkinson's disease (currently administered subcutaneously as bolus injections) and only in the EU and not in the United States for continuous, subcutaneously delivered chronic therapy of advanced Parkinson's patients. Current commercial apomorphine formulations, based on apomorphine-HCl, are associated with low tolerability and local pain and require daily subcutaneous administration of large volumes that limit its more widespread adoption. ND0701 is being developed as a chronic therapy of Parkinson's disease by continuous subcutaneous apomorphine administration. Based on a proprietary formulation of apomorphine-base, ND0701 is up to five times more concentrated than currently available commercial apomorphine-HCl products and should enable delivery through a small, low-volume, disposable patch-pump. In pre-clinical studies, ND0701 was also shown to have better local tolerability in pre-clinical studies than a leading commercial apomorphine product. ND0701 is designed to offer superior convenience and better tolerability to current, continuous, subcutaneously administered apomorphine-HCl products.

About Parkinson's disease
Parkinson's disease is a progressive neurodegenerative illness characterized by reduced dopamine in the brain, resulting in a debilitating decrease in the patient's motor and non-motor functions. Its symptoms, such as trembling in the extremities and face, slowness of movement and impaired balance and coordination, worsen over time and gravely impact the patient's quality of life. It has been shown that continuous administration of dopaminergic therapies, levodopa or apomorphine, can effectively treat motor fluctuations in Parkinson's disease patients without increasing troublesome dyskinesia.

About NeuroDerm
NeuroDerm is a clinical-stage pharmaceutical Company developing central nervous system (CNS) product candidates that are designed to overcome major deficiencies of current treatments and achieve enhanced clinical efficacy through continuous, controlled administration. The Company has three product candidates in different stages of development which offer a solution for almost every Parkinson’s disease patient from the moderate to the very severe stage of the disease. The Company has developed a line of levodopa and carbidopa (LD/CD) product candidates administered through small belt pumps that deliver a continuous, controlled dose of LD/CD. The LD/CD product candidates are ND0612L and ND0612H, which are used for treatment of moderate and advanced Parkinson’s disease patients, respectively, and which are delivered subcutaneously. In addition, NeuroDerm is developing ND0701, a novel subcutaneously delivered apomorphine formulation for patients who suffer from moderate to severe Parkinson’s disease and who do not respond well to LD/CD. NeuroDerm is headquartered in the Weizmann Science Park in Rehovot, Israel.

Forward-Looking Statements
This press release contains forward-looking statements, within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended that involve risks and uncertainties. Such forward-looking statements may include projections regarding our future performance and may be identified by words like "anticipate," "assume," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "future," "will," "seek" and similar terms or phrases. The forward-looking statements contained in this press release are based on management's current expectations and projections about future events. There are important factors that could cause our actual results, levels of activity, performance or achievements to differ materially from the results, levels of activity, performance or achievements expressed or implied by the forward-looking statements. In particular, you should consider the risks provided under "Risk Factors" in our annual report on Form 20-F for the year ended December 31, 2015 filed with the Securities and Exchange Commission. Any forward-looking statement made by us in this press release speaks only as of the date hereof. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

NeuroDerm Contact:

Oded S. Lieberman, PhD, CEO

oded@neuroderm.com

Tel.: +972-8-946 2729; Cell: +1-617-517 6077

U.S. Investor Contact:

David Carey

Lazar Partners Ltd.

dcarey@lazarpartners.com

+212-867-1768

U.S. Media Contact:

Erich Sandoval

Lazar Partners Ltd.

esandoval@lazarpartners.com

+917-497-2867

http://www.globenewswire.com/news-release/2016/12/02/894639/0/en/NeuroDerm-Announces-Top-Line-Results-of-Pilot-PK-Trial-Comparing-ND0701-with-Commercial-Apomorphine.html

FoxFeed Blog: Mutations in GBA Gene Linked to Parkinson's Cognitive Decline

Maggie McGuire Kuhl 

 December 01, 2016

Dr. Clemens Scherzer, middle, led one of the studies and is further investigating GBA with MJFF support.

As we learn more about genetic connections to Parkinson's disease (PD), researchers strive to understand the biological and functional impact of these variants. What does having a GBAmutation really mean for someone? Complicating matters further is that there are many different mutations on one gene. How does the type of mutation on that gene impact PD? (Learn more about genetics.)

Findings from two studies, one MJFF-funded, published recently in Annals of Neurology point to mutations in the GBA gene that may predispose some to cognitive problems with Parkinson's disease. 

GBA Mutations Linked to Cognitive Decline

The MJFF-funded study, from researchers at Brigham and Women's Hospital (BWH) in Boston and the International Genetics of Parkinson Disease Progression Consortium, screened samples from more than 2,300 people with PD gathered from seven studies. The researchers found around 10 percent had a GBAmutation and classified some mutations as severe (so-called neuropathic mutations). About one to two percent of people in the studies had severe GBA mutations.

The paper reported having any kind of GBA mutation was linked to higher risk of cognitive decline, but those with a severe mutation saw their risk increase over time by 217 percent. Ten years after diagnosis, 50 percent of people with a severe GBA mutation had cognitive impairment compared to only 20 percent of people without a GBA mutation.

The other study, from a team at the Institute for Parkinson's Disease and Movement Disorders in Milan, Italy, looked at data from more than 2,800 people with PD seen there. They, too, found a GBA mutation was associated with higher risk of dementia and the risk was greater with mutations identified as severe.

Findings May Inform How We Develop Therapies

Mutations in the GBA gene lead to lower levels of the GCase protein, which are associated with more clumps of the protein alpha-synuclein. Scientists believe those clumps harm cells and cause PD progression. (Read more about GBA and GCase.) Researchers are working on therapies to address GCase dysfunction in people with GBA mutations, with some close to clinical trials.

The findings linking these mutations to cognitive dysfunction may offer a way to test the effects of those therapies.

In an accompanying commentary also published in Annals of Neurology, David Standaert, MD, PhD, a member of the MJFF Scientific Advisory Board, and David Geldmacher, MD, both of the University of Alabama at Birmingham (UAB) and not affiliated with the studies, wrote, "Use of cognitive endpoints may be a valuable strategy in these studies, as the rapid rate of decline observed provides a robust signal and may reduce the sample size and duration required in these studies."

To further enable drug development and testing, our Foundation is funding an initiative led by Clemens Scherzer, MD, who also led the BWH study, to investigate biological markers of Parkinson's in people with a GBA mutation and make more connections between genetics and the clinical presentation of the disease.

"This is the dawn of personalized medicine for Parkinson's disease," said Dr. Scherzer. "We see more precise clinical trials as the next logical step, and one that will help match the right therapies with the right patients faster."

Genetics Testing Can Inform Research but Not Yet Care

The UAB authors' commentary also acknowledges the impact of these findings on individuals' care. Should people be genetically tested for GBA to predict cognitive decline? Drs. Standaert and Geldmacher say some patients may want that information, although at this time there is no specific treatment for PD cognition. Also, there may be other factors that influence cognitive decline, so a negative GBA test may give a false sense of security.

Those who do have a GBA mutation can help us learn more about the disease and develop new treatments. Mutations in this gene are more common in people of Ashkenazi Jewish descent and are associated with Gaucher disease, a disorder where fatty substances build up and cause enlarged organs. The MJFF-led Parkinson's Progression Markers Initiative (PPMI) -- a study to identify biological markers of PD and learn more about its genetics -- is enrolling people of Ashkenazi Jewish descent with PD or Gaucher or a first-degree relative with one of the two diseases.

https://www.michaeljfox.org/foundation/news-detail.php?mutations-in-gba-gene-linked-to-parkinson-cognitive-decline