technology

3 Ways Connecting to Tech Can Help Keep Seniors Connected

October 1, 2020 Caregivers, Life

In this fast-paced world, staying connected can be difficult enough for seniors. Add in a pandemic for which people 65+ are most vulnerable, and you have a situation that can lead to intense feelings of isolation, loneliness and hopelessness. But through technology, seniors can stay connect in meaningful ways, such as:

Safely Accessing Resources

Whether due to physical limitations, weather or current events, sometimes it’s impossible for seniors to get out and explore their communities. This makes it important for older adults to be able to access a working home internet connection, both for purposes of socializing and for safety’s sake. Ideally, seniors should have access to both a senior-friendly device and a solid internet connection.

Electronics are increasingly senior-friendly, with both smartphones and tablets worth considering. Internet access can be a challenge, though.

For seniors living in more rural areas, Verizon’s home internet service can be a practical and affordable option for seniors, connecting them to one of the most reliable networks in the nation. With a powerful connection, seniors can access resources like support groups for Parkinson’s, or safely discuss issues with healthcare providers via telehealth appointments.

Regularly Checking In With Long-Distance Loved Ones

Being geographically separated from family can be especially burdensome for seniors. When travel for families is not an option, seniors can start feeling the effects of isolation and depression, both of which are growing issues within aging populations. Seniors may feel unloved, forgotten or without a sense of purpose when they are unable to connect with those they care about.

Thankfully, aging family members can reach out to long-distance family members via social media. Social media has become a sort of safe haven for senior mental health, but there may be times when seniors crave actual face time. As CNBC notes, video chat apps are increasingly useful for maintaining healthy connections.

Staying Safe, Comfortable and Secure While Aging in Place

When visiting with an aging family member is not possible or practical, aging in place tech can assist with staying abreast of well-being from afar.

For instance, a smart home security system that helps aging family members feel protected at home can double as a monitoring system for long-distance caregivers. Virtual assistants allow caregivers to check in with senior loved ones, plus they provide seniors with a sense of comfort. If a senior has mobility issues that makes moving around difficult or even dangerous, smart home options like automated lighting provide peace of mind.

Tech can be a priceless tool when it comes to protecting seniors and preserving their quality of life. Instead of feeling isolated, seniors can use tech to stay connected to the people they love.

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A Wearable Device Is Changing the Way Clinicians Manage PD

November 1, 2019 Education, Life, Research

A recently published study in Functional Neurology suggests that using data from an FDA-cleared watch-like device called the Personal KinetiGraph (PKG) provides an objective and more effective approach to assessing motor fluctuations in patients with Parkinson’s disease (PD) compared with patient-reported motor diaries.

“Motor fluctuations, including ‘wearing-off’ and dyskinesia, are associated with increased disease severity and disability, and PD patients experience decreased quality of life as their response to medical therapy becomes less predictable,” said Echo Tan, MD, a neurologist at Cedars-Sinai Medical Center and lead author on the publication. “Effectively managing motor fluctuations is complicated by the lack of objective assessment tools, leading patients and physicians to rely on direct observation in the clinic or patient reports, which may be unrevealing, incomplete and unreliable. The results of our study demonstrate that the fluctuation score calculated by the PKG system provides objective quantification of motor fluctuations.”

This may help improve the routine management of Parkinson’s patients and enable more objective assessments in clinical trials of Parkinson’s therapies, she said.

Tan told MD+DI the study revealed that the PKG system (developed by Global Kinetics) and the algorithms for calculating a fluctuator score can differentiate between non-dyskinetic and dyskinetic patients. The fluctuator score does not, however, have the sensitivity to detect mild wearing off because no prior study divided patients into more than a binary system. On the plus side, Tan said the PKG also can distinguish between exercise and dyskinesia on the graphical data obtained.

The fact that the fluctuator score was not sensitive enough to detect mild wearing off did come as a surprise to the investigators, but the fluctuator score did show progressively increasing average score range between the four groups, Tan said.

During a BIOMEDevice Boston 2019 panel discussion, Teresa Prego, vice president of marketing and marketing development at the Melbourne, Australia-based company, said the integration of consumer wearables with wearables for chronic disease management has changed the delivery of care and where that care is delivered.

“If I look at the PKG-Watch, for example, in Australia where there are great geographic distances between people with Parkinson’s and a care provider. They are using this remotely,” Prego said. “So you’ll go and see your clinician, have an assessment, but then for the next year, there’s really no need to go into the clinic. You can make care decisions remotely. They’re wearing the vehicles to get that information to the clinician.”

“This implies that it is better at detecting moderate to severe fluctuations,” she said.

Most importantly, the device has changed the way Tan and her colleagues assess and monitor patients with Parkinson’s disease.

“The PKG system can provide additional information about fluctuations that a clinic visit and history can not reveal,” she said. “This is particularly useful for those patients who are not able to provide a good history – such as those with a language barrier or cognitive impairment. It can show true objective levodopa responsiveness, motor fluctuations, daytime somnolence, and medication compliance. “It can be an important triage mechanism for a referral to a movement disorder specialist, or for an advanced surgical therapy referral. It has provided another objective source of information for our clinicians in deciding how to change medical management. Patients also report that the medication reminder function on the device helps them with medication compliance, thereby also enhancing their motor function as well.”

Parkinson’s disease patients typically respond well to medical therapy in the first few years of their disease, but about 40% of the patient population develops fluctuations of response to levodopa and dyskinesia after four to six years of treatment. That percentage jumps to 70% after long-term treatment of nine years or more, according to Global Kinetics. The company said it developed the PKG system to address the lack of objective measurement tools for movement disorders and quantifies the kinematics of Parkinson’s symptoms, including tremor, bradykinesia, and dyskinesia. An algorithm translates the raw data from these assessments into a fluctuation score that can distinguish between patients with motor fluctuations and those without.

The study investigators correlated PKG fluctuator scores (FS) with clinical motor fluctuator profiles in a case-controlled cohort of the study that included 60 patients attending the Movement Disorders Clinic at Cedars-Sinai Medical Center in Los Angeles, CA. Of the 60 patients in the study, six had incomplete data and were excluded from analyses, the company noted.

Here are some key findings from the 54 subjects who completed a six-day PKG trial and completed a standardized motor diary:

  • Based on Wearing Off Questionnaire (WOQ9) and Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part IV scores patients were categorized based on the presence and extent of fluctuations, as follows:
    • Non-fluctuators (NF), N = 14
    • Early fluctuators (EF), N = 15
    • Moderate fluctuators (MF), N = 15
    • Troublesome fluctuators (TF), N = 10
  • The groups varied significantly in terms of disease duration, which was progressively longer with increasing severity of clinical fluctuation and PD dopamine medication measured as levodopa equivalent dose (LED).
  • LED was more than double in patients with troublesome fluctuations compared to those without fluctuations, while patients in the groups including early and moderate fluctuators reported equivalent daily dosages.
  • MDS-UPDRS score increased significantly with the severity of fluctuations, with the highest scores recorded in those with troublesome fluctuations.
  • Patients had a higher tendency to return the PKG than the motor diary (88% vs. 65%).
  • 50% of the patients in the troublesome fluctuator group were excluded due to incorrect diary completion.
  • Compliance with the motor diary improved with decreasing severity of fluctuations.
  • PKG fluctuation score significantly differentiated EF and TF (p = 0.01), as well as dyskinetic and non-dyskinetic subjects (p < 0.005). In contrast, motor diaries could not distinguish the four study groups on the basis of average OFF time, while average time with dyskinesia distinguished NF and MF but did not distinguish among all four groups.
  • PKG identified high levels of dyskinesia in patients who denied having dyskinesia.

The study authors conclude that the data support the use of the PKG fluctuation score as an objective tool for capturing and quantifying motor fluctuations as a mechanism for triaging PD patients. They also note that the PKG transcends language and cognitive barriers and time constraints in the clinic, which are challenges to obtaining accurate patient symptoms to effectively adjust PD treatment.

The main barrier to adoption for products like these is reimbursement, Prego noted.

“Capturing this data and utilizing the advent of these consumer technologies to help manage chronic disease, it’s pretty interesting,” she said. “I think that our traditional ways of reimbursing for medical care have not quite caught up to where the development of consumer wearables has taken us.”

Article from MD+DI.

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Could this newly discovered protein help treat Parkinson’s?

August 1, 2019 Education, Research
Researchers have found a protein that could help reduce the aggregation of toxic proteins in the brain — a hallmark of Parkinson’s disease. But does their discovery offer fresh hope or just “a Band-Aid?”

Does a new discovery reveal a fresh research pathway for Parkinson’s therapy?

The National Institutes of Health estimate that, in the United States, around 50,000 peoplereceive a Parkinson’s disease diagnosis each year.

This widespread condition is characterized by tremors, slowness of movement, and impaired balance and coordination, among other symptoms.

However, its causes remain unknown and treatments only target the symptoms, helping individuals to manage this condition as best they can.

In the brain, Parkinson’s is characterized by a puzzling feature — the aggregation of alpha-synuclein, a protein that becomes toxic and disrupts the neural pathways when it sticks together in large quantities.

This occurs when alpha-synuclein misfolds, that is, when it folds into an incorrect shape that does not allow it to function correctly, which may cause or facilitate disease.

Alpha-synuclein is typically present at high levels in the brain, and it is also present in other tissue in smaller amounts. Still, researchers have no idea what role this protein usually plays in maintaining neural health or how to prevent it from misfolding.

But a new study, from Purdue University, in West Lafayette, IN, has identified a protein able to reduce the aggregation of misfolded alpha-synuclein. The findings feature in the Journal of Molecular Biology.

How HYPE may reduce aggregation

The new research has focused on the therapeutic potential of a protein called “HYPE,” which, the investigators explain, is the only Fic protein present in humans.

Fic proteins help decide whether a cell survives or dies when it encounters stress, characterized by the misfolding of the cell’s proteins.

“Since HYPE plays such an important role in how cells deal with stress from misfolded proteins, we wondered whether diseases that result from protein misfolding were likely to need HYPE,” explains lead study author Seema Mattoo, Ph.D., an assistant professor of biological sciences at Purdue.

She continues: “We know that in Parkinson’s disease, often the misfolded protein is [alpha-synuclein]. So we asked if HYPE could modify [alpha-synuclein], and if so, what are the consequences?”

In the current study — which the researchers conducted in vitro, using cell cultures in a laboratory setting — they found that HYPE can indeed act on alpha-synuclein, decreasing the amount of aggregation of misfolded proteins. The researchers call this process “AMPylation.”

Then, the team wanted to see if AMPylation actually showed any promise as a potential therapeutic process. In Parkinson’s disease, aggregated, misfolded proteins can puncture the membranes of neurons (brain cells), disrupting their functioning.

Mattoo and colleagues wanted to find out whether AMPylation would also lead to fewer holes in the membranes of cells. To do so, they used a combination of lipids to create a surface simulating that of cell membranes.

They also added dye to the lipids, so if alpha-synuclein aggregates punctured them, the action would become visible through leaked dye.

After doing so, Mattoo notes, “We found that less dye was released with the modified [alpha-synuclein], meaning the membrane stayed more intact.”

“That means HYPE could possibly have a therapeutic effect on Parkinson’s disease,” she adds. Moreover, as Mattoo and colleagues note in their study paper, “This is the first report identifying [alpha-synuclein] as a target for HYPE.”

Going beyond the ‘Band-Aid?’

In a final experiment, Mattoo and the team studied HYPE-modified alpha-synuclein using an electron microscope. This allowed them to observe that, after interacting with HYPE, alpha-synuclein’s structure had changed.

Under regular circumstances, the researchers note, alpha-synuclein twists, which may explain its potential to form aggregates. However, when modified by HYPE, the protein tended to twist less, instead forming parallel strands.

This new modification, the researchers argue, may prevent alpha-synuclein from aggregating as much.

While the current research shows promise in finding new therapies for Parkinson’s disease, the study authors explain that they still have a long way to go.

“We’re in the early stages [of this research],” Mattoo admits, “but these results are giving us a new angle to look at potential therapeutics.”

“We’re trying to come up with drugs that could be used to manipulate HYPE’s activity. You could give them to patients who are starting to show signs of Parkinson’s or who are prone to having aggregated [alpha-synuclein]. That’s the direction we want to go [in],” the researcher explains.

Article from Medical News Today.

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Developing a Biomarker for Parkinson Disease

June 1, 2019 Education, Research

Identifying, studying, and verifying a potential biomarker can be a lengthy affair. However, success often means clinicians have a new tool to better diagnose a condition like Parkinson disease and to diagnose the condition earlier in the disease progression.

A biomarker for Parkinson disease might mean that patients can begin receiving treatment before irreversible neurological damage occurs.

Sarah Hamm-Alvarez, PhD, Professor of Ophthalmology at the USC Roski Eye Institute at the Keck School of Medicine of USC, spoke with MD Magazine® about this biomarker research, which she presented at the 2019 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Vancouver, BC.

Hamm-Alvarez highlighted the collaborative nature of the project that has included colleagues from the neurology, pharmacy, and preventive medicine departments.

“Part of the passion for the project is driven by the clinical need that I sense from my neurology colleagues and their frustration that they don’t have better ways to diagnose patients at early disease states,” said Hamm-Alvarez.

In part 1 of the interview, Hamm-Alvarez introduced the study and the team’s reasons for investigating tears for a Parkinson biomarker. In part 2, she described the study methods and the differences they found in basal and reflex tears.

What’s the process for developing a biomarker?

First you start by establishing a correlation, which we have done. And right now what we’re doing is that we are actually recruiting patients with Parkinson’s disease that are at different times from disease diagnosis and this, we think, will reflect disease severity. So, what we’re trying to do is to see if the levels of oligomeric α-synuclein are correlated with time from disease diagnosis. So, we’re going to try to get a sense of the disease severity. We also are eventually planning to try to test this in patients without a diagnosis, as well as patients who exhibit symptoms that overlap with Parkinson’s disease, such as patients with atypical parkinsonian syndromes and patients with other neurological disorders, of course, to determine how specific this may be, and also whether this has predictive ability going forward if a patient is at an early stage of Parkinson’s disease.

How have various departments collaborated in this project?

This project is very much a team effort we have a whole team at the University of Southern California including colleagues in neurology and pharmacy and preventive medicine. We work very closely with Mark Liu in neurology, who is a neurologist, and who is very excited about the potential for applying this in his clinic. So, I think that part of the passion for the project is driven by the clinical need that I sense from my neurology colleagues and their frustration that they don’t have better ways to diagnose patients at early disease states.

Article from MD Magazine.

 

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Virtual reality reduced PD symptoms for 10 people

June 1, 2019 Life, Research

A new virtual reality game has helped Parkinson’s sufferers keep walking without losing their balance, falling or struggling to turn.

Over time, the incurable neurodegenerative disease restricts muscles more and more, limiting a person’s mobility, ability to turn and balance. But a new technique developed by researchers at the University of Utah restored dynamic movement in 10 patients who trained on the system three times a week for six weeks.

Experts believe the repetitive activity – walking, running and turning on a treadmill as they hop over virtual objects on a cave-like screen in front of them – helped to keep their muscle memory active and ward off deterioration.

‘The primary advantage is that they can encounter multiple obstacles and terrains while a safe environment is maintained using equipment such as a fall restraint tether,’ said K. Bo Foreman, PhD, associate professor and director of the Motion Capture Core Facility at the University of Utah.

‘Participants enjoyed the experience and thought it was fun, not just exercise. They liked training and challenging themselves without the fear of falling.’

The virtual reality experience is projected onto semi-circle-shaped wall facing the patient, who is on a very wide treadmill. The patient wears a headset, shoes and clothing with sensors on them, and they are tethered to a pole behind them for control.

Some of the tasks seem more straight forward than others – walking straight through a field, for example, rather than jumping up onto the curb of a road. But the fusion of everything together forces patients to exercise various skills which can quickly become challenging, if not impossible, for people with Parkinson’s.

Once we’ve learned to walk, we become adept at nimbly switching from walking to running, from walking straight forward, to walking diagonally to the right. We can speed up or slow down, and step to the left or right, or up or down.

Researchers are still working to fully understand how Parkinson’s restricts movement and gait. There is evidence that the drop in dopamine levels plays a role. However, there is growing evidence that physical activity can stave off the decline. For example, revered actor Alan Alda, who revealed his Parkinson’s diagnosis last summer, has taken up boxing to stay mobile.

Dr Foreman’s team at Utah believe VR, much-hyped for its potential use in clinics, is worth the fan-fare. ‘We are hopeful that this improved performance relates to decreased falls in their everyday life,’ Dr Foreman said. ‘Parkinson’s disease is a progressive disease, and anything we can do to impact the progression is a step in the right direction.’

Article from Daily Mail.

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WPA on the Radio!

April 1, 2019 Education, Life

WPA Executive Director Gary Garland was interviewed by Milwaukee Radio Group host Andrea Williams last week. Listen here!

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Manganese and Parkinson’s: Mechanism may explain link

April 1, 2019 Research
New research, published in the journal Science Signaling, details the mechanism through which exposure to manganese can trigger protein misfolding in the brain — which may, in turn, lead to Parkinson’s-like symptoms. The findings may enable an earlier diagnosis of the neurological condition.
Manganese is an essential nutrient present in “legumes, pineapples, beans, nuts, tea, and grains.”

In the human body, manganese aids blood sugar regulation, bone formation, and immunity.

However, exposure to excessive levels of manganese may trigger Parkinson’s-like neurological symptoms. Manganese builds up in the basal ganglia area of the brain.

Researchers have known about these links between manganese and Parkinson’s for decades, but new research helps elucidate the mechanisms behind these associations.

Anumantha Kanthasamy, the Linda Lloyd Endowed Chair of Neurotoxicology at Iowa State University in Ames, led the new research.

Manganese helps transfer a faulty protein

Parkinson’s disease is characterized by clumps formed by misfolded alpha-synuclein protein. These protein aggregates are toxic to neurons.

Kanthasamy and colleagues set out to investigate how these misfolding proteins might interact with manganese to trigger the progression of Parkinson’s.

To do so, they examined data from mice and blood serum samples collected from eight welders. As a group, welders have a higher risk of prolonged manganese exposure. The research also examined a control group of 10 people.

The analyses revealed that welders with exposure to manganese had higher levels of misfolded alpha-synuclein, which puts them at a higher risk of Parkinson’s.

Additional cell culture tests showed that misfolded alpha-synuclein was secreted through small vesicles called exosomes into the extracellular space. In other words, the vesicles enabled the proteins to travel from cell to cell and further spread the misfolded protein.

The scientists also isolated alpha-synuclein-containing exosomes from alpha-synuclein-expressing cells that had exposure to manganese and delivered them to a brain area in the mice called the corpus striatum. This induced Parkinson’s-like symptoms in the mice.

Manganese seemed to accelerate the “cell-to-cell transmission” of alpha-synuclein, which, in turn, led to neurotoxicity. Kanthasamy and colleagues explain:

“Together, these results indicate that [manganese] exposure promotes [alpha-synuclein] secretion in exosomal vesicles, which subsequently evokes proinflammatory and neurodegenerative responses in both cell culture and animal models.”

“[W]e identified a possible mechanism involving the exosome-mediated, cell-to-cell transmission of [alpha-synuclein] during exposure to the environmental neurotoxicant,” write the authors.

Findings may lead to earlier detection

According to the National Institutes of Health (NIH), around 50,000 individuals in the United States receive a diagnosis of Parkinson’s each year, and 500,000 people currently live with the condition.

Though the condition does not yet have a cure, diagnosing it earlier may prevent irreversible brain damage and help accelerate human clinical trials of new drugs.

The results that Kanthasamy and colleagues have just published may help scientists devise a new diagnostic test for Parkinson’s that could detect the disease much earlier on. The results may also help scientists test how effective new Parkinson’s drugs are.

“As the disease advances, it’s harder to slow it down with treatments,” Kanthasamy says. He adds: “Earlier detection, perhaps by testing for misfolded alpha-synuclein, can lead to better outcomes for patients. Such a test might also indicate whether someone is at risk before the onset of the disease.”

However, the study authors also caution that their findings are still experimental, and that such a diagnostic test may not be available for years.

Article from Medical News Today.

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Top Senior Scams to be on the Lookout For

February 1, 2019 Awareness, Caregivers, Education, Life

Eras Senior Network of Waukesha County coordinates S.T.O.P. – an awareness program focusing on frauds and scams aimed at older adults.

In 2014, the Federal Trade Commission created the Pass it ON campaign aimed at encouraging people to share vital information about scams. The FTC encourages you to not only share gifts and food during the holidays, but also tips about scams targeting older adults.

Since 2016, Eras Senior Network has given 47 presentations to over 1,250 seniors and their caregivers about common scams targeting the senior population. Through our research and conversations with seniors who have experienced interactions with scam artists, we’ve collected a list of popular senior scams that we hope you’ll share with those you love.

Grandparent Scam: A scam artist calls a senior and says “Hi Grandma, it’s me!” Oftentimes the senior assumes they’re speaking to their grandchild and won’t even ask for a name. Sometimes, the scam artist pretends to be crying, which distorts their voice, making it easier for the senior to believe it could be their grandchild. The scammer will then tell the senior they are in some sort of trouble and will need money wired to them – and begs their “grandparent” not to tell their “parents”. To avoid this scam, ask the caller specific questions like their name, address, or something only your true grandchild would know – and never wire money or send gift cards through the internet!

Telemarketing “Yes” Scam: Telemarketing scam artists use a simple response to steal from you. In this scam, a senior will receive a call and be asked if they can hear the caller. The natural response is to say “yes”. Unfortunately, scam artists can record this response and use it to fraudulently authorize charges via the telephone, according to the Federal Communications Commission. The best way to avoid this is by screening your calls and only answering numbers you recognize, or finding another way to answer their question without saying the word “yes.”

Medicare Card Scams: As you may know, new Medicare cards without the individual’s social security number began being mailed in April 2018. With this comes the risk for Medicare related scams as predicted by the Better Business Bureau. Scam artists may ask you for your social security number or a payment in order to receive your card. Your new Medicare card will be sent to you automatically at no charge – you DO NOT need to do anything or pay anything for your new Medicare card to be mailed to you.

Spear Phishing: Spear phishing is an email or electronic communications scam targeted towards a specific individual, organization or business. Emails that look like they are from a friend or family member can actually be attempts to steal data. Before clicking on the message, hover your mouse (without clicking) above the sender’s email address to see if it is from the person you know. Phone calls may showing caller identification from a known person can also be spear phishing attempts. Once you realize the caller isn’t your friend or family member, hang up without saying anything!

Sharing what you know about frauds and scams may be the best gift you can give someone. If you feel like you have been a victim of a fraud or scam, contact your local police department by calling their non-emergency number.

Kathy Gale is Executive Director, Eras Senior Network, Inc. and a member of the Wisconsin Attorney General’s Task Force on Elder Abuse. S.T.O.P. Senior Frauds and Scams is brought to you by Eras through a grant from the Wisconsin Consumer Antifraud Fund at the Greater Milwaukee Foundation and the United Way of Greater Milwaukee and Waukesha County. More information about Eras Senior Network, Inc. can be found at www.ErasWaukesha.org.

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Irish entrepreneur uses technology to fight PD

October 1, 2018 Community Outreach, Life, Research

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

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

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

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

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

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

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

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

Article from JOE.ie.

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Protein might become candidate for drug development

October 1, 2018 Research

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

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

Bacterial protein building block as import signal

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

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

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

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

Protein protects from the effects of neurotoxin

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

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

Article from Ruhr University Bochum.

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