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Parkinson's

$3m study to tackle unknowns of Parkinson’s disease

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A $3million study has been launched to answer some of the key unknown factors that persist around Parkinson’s disease. 

The five-year project, known as ENIGMA-PD, will analyse brain imaging, genetics, and clinical data in one of the world’s largest studies of the disease.

It will unite researchers and data from 20 countries to address some of the main questions around the condition. The project will be led by the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (USC Stevens INI).

“This new grant will tackle some of the major puzzles about how PD progresses in the brain, and how treatment can protect against those changes,” said Dr Paul M. Thompson, principal investigator of the new initiative and associate director of the USC Stevens INI.

The researchers have already conducted one of the largest internationally coordinated analyses of Parkinson’s brain imaging data. 

They studied structural differences between 1,182 healthy brains and 2,357 affected by Parkinson’s, identifying a characteristic pattern of tissue damage that began in the brain’s temporal lobes and spreads throughout the cortex.

Those findings challenge the conventional wisdom about Parkinson’s, which holds that deeper regions of the brain are damaged first and may hint at multiple Parkinson’s subtypes with different courses and treatments. 

ENIGMA-PD will study whether treatments, including drugs such as L-Dopa and surgical therapies such as Deep Brain Stimulation, can slow down this progression of brain tissue loss and clinical decline. 

Researchers will also investigate genetic factors that contribute to Parkinson’s risk, with a particular focus on how different genes increase the risk of developing the condition in individuals with European versus Asian ancestry.

“What’s unique about this project is that it engages experts from across the globe, which will be crucial for understanding how Parkinson’s risk and progression may differ depending on a person’s genetic background,” said Dr Thompson, who is also a professor of ophthalmology, neurology, psychiatry and the behavioural sciences, radiology and engineering at the Keck School of Medicine.

ENIGMA-PD builds on the success of the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, which unites neuroimaging researchers in 45 countries to study a variety brain diseases and processes.

Founded in 2009, the ENIGMA network has conducted some of the world’s largest neuroimaging studies of schizophrenia, bipolar disorder, major depression, epilepsy, and other conditions affecting the brain.

The project adds to the INI’s ongoing work on PD, which began in 2010 with the launch of the Parkinson’s Progression Markers Initiative (PPMI). The institute stores all the clinical, genetic and imaging data for more than 1,400 individuals in the PPMI study, which is sponsored by the Michael J. Fox Foundation.

Parkinson's

Seven strategies to help people with Parkinson’s improve their walking

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Seven strategies can help people with Parkinson’s who have difficulty walking, a new study has revealed. 

Compensation strategies can be effective for those with disabling gait impairments – the seven are: 

  • internal cueing, like walking to a count in your head 
  • external cueing, like walking in rhythm to a metronome 
  • changing the balance requirement, like making wider turns 
  • altering mental state, which includes relaxation techniques 
  • action observation and motor imagery, which includes watching another person walk 
  • adapting a new walking pattern, like jumping or walking backwards 
  • other forms of using the legs, like cycling and crawling.

The study – which revealed that many people had never heard of or tried these strategies – also found their efficacy depended on the context in which they were used, such as indoors versus outdoors, under time pressure or not.

We know people with Parkinson’s often spontaneously invent creative ‘detours’ to overcome their walking difficulties, in order to remain mobile and independent,” said study author Anouk Tosserams, of the Radboud University Medical Centre in Nijmegen, the Netherlands. 

“For example, people walk to the rhythm of a metronome, by mimicking the gait of another person, or by counting in their head. We found that people are rarely educated about all the different compensation strategies. 

“When they are, people often find strategies that work better for them and their unique circumstances.”

For the study, researchers surveyed 4,324 people with Parkinson’s and disabling gait impairments. These include problems like imbalance, shuffling, falling, staggering and freezing. 

Of the participants, 35 per cent found that their walking difficulties affected their ability to perform their usual daily activities and 52 per cent had one or more falls in the past year.

The survey focused on the seven main categories of compensation strategies. Each category was explained and participants were asked if they were aware of it, if they’d ever used it, and if so, how it worked for them in a variety of contexts.

Researchers found that people with Parkinson’s commonly use walking compensation strategies, but are not aware of all seven strategies. For example, 17 per cent of the people had never heard of any of these strategies, and 23 per cent had never tried any of them. 

Only four per cent were aware of all seven categories of compensation strategies. The average person knew about three strategies. 

For each strategy, the majority of people who tried it said it had a positive effect. 76 per cent said changing the balance requirement made a positive impact, while 74 per cent said altering their mental state did.

However, researchers also discovered that strategies worked differently according to the context in which the person used it. Internal cueing, for example, seemed highly effective during gait initiation, with a 73 per cent success rate – but only 47 per cent found that tactic useful when trying to stop walking. 

“Our findings suggest that a ‘one-size-fits-all’ approach doesn’t work, because different contexts might require different strategies, or because individuals simply respond better to one strategy compared to another,” Dr Tosserams said. 

“We need to go a step further and teach people about all the available compensation strategies, for example through a dedicated online educational platform. This may help each person with Parkinson’s find the strategy that works best for them.”

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Recycling a “cell’s energy centres” could ward off Parkinson’s

Study suggests re-energising of cells linked to fighting the disease.

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Scientists have long known that living cells are master recyclers, constantly breaking down old parts and building them back up into new molecular machines.

Now, researchers have taken a closer look at the life cycle of energy-generating cellular power plants—called mitochondria— inside brain cells, and how they might be recycled. They showed that genes associated with Parkinson’s disease play key roles in this process.

“This work gives us unprecedented insight into mitochondria’s life cycle and how they are recycled by key proteins that, when mutated,  cause Parkinson’s disease,” says Gladstone Associate Investigator Ken Nakamura, MD, PhD, senior author of the new study.

“It suggests that mitochondrial recycling is critical to maintaining healthy mitochondria, and disruptions to this process can contribute to neurodegeneration.”

In most cells, damaged mitochondria are decomposed in a process known as mitophagy, which is initiated by two proteins, PINK1 and Parkin.

Mutations in these same proteins also cause hereditary forms of Parkinson’s disease. While the role of PINK1 and Parkin in mitophagy has been heavily studied in many cell types, it has been unclear whether these proteins act the same way in neurons—the type of brain cells that die in Parkinson’s disease. Indeed, neurons have unusually high energy needs and their mitochondria are much more resistant to degradation by Parkin than those in other cell types.

In the new study published in the journal Science Advances, Nakamura’s group followed mitochondria inside living neurons and examined how PINK1 and Parkin affected their fate.

But mitochondria are small and they move inside cells, frequently fusing with each other or splitting in two, which makes them difficult to track.

“We had to develop a new way of tracking individual mitochondria over long periods of time, almost a full day,” says Zak Doric, a graduate student at Gladstone and UC San Francisco (UCSF) and co-first author of the new study. “Getting that technique up and running was quite a challenge.”

The scientists also used a method that allowed them to generate larger-than-normal mitochondria, making them easier to see under a microscope.

They found that Parkin proteins encircled damaged mitochondria and targeted them for degradation, demonstrating that mitophagy starts in neurons in the same way as in other cell types. But thanks to their new approach, they could watch the process unfold in great detail.

For instance, they documented the key initial steps in which damaged, Parkin-coated mitochondria fuse with other components inside the cell to form mitochondria-degrading structures called mitolysosomes.

“We were able to visualise these steps at a level that hasn’t been done before in any cell type,” says Nakamura, who is also an associate professor of neurology at UCSF.

The high resolution of their approach will allow them to understand with great precision how Parkin and PINK1 affect mitochondrial degradation in Parkinson’s disease.

A New Kind of Recycling

The researchers then examined the later phases of mitophagy, monitoring what happens to mitochondria in the mitolysosomes.

“Until now, nobody has known what happens next to these mitolysosomes,” says Nakamura.

So far, scientists had assumed that mitolysosomes rapidly break down into molecules that the cell can reuse to build new mitochondria from scratch. Nakamura and his team showed that, instead, the mitolysosomes survived for hours inside cells.

Unexpectedly, some mitolysosomes were engulfed by healthy mitochondria, while other times, they suddenly burst, releasing their contents into the interior of the cell, including some proteins that were still functional.

“This appears to be a new mitochondrial quality control, recycling system,” says Huihui Li, PhD, a Gladstone postdoctoral scholar and co-first author of the new paper. “We think we’ve uncovered a pathway of mitochondrial recycling—which is like salvaging valuable furniture in a house before demolishing it.”

Importantly, the study shows that the recycling pathway identified by the scientists requires PINK1 and Parkin, supporting that mitochondrial recycling may also be critical in protecting against neurodegeneration in Parkinson’s disease.

“Dopamine neurons that die in Parkinson’s disease are particularly susceptible to mutations in PINK1 and Parkin,” says Nakamura. “Our study advances our understanding of how these two key Parkinson’s disease proteins degrade and recycle mitochondria. Our future studies will investigate how these pathways contribute to disease and how they can be targeted therapeutically.”

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Dementia

The Robo pets helping dementia and Parkinson’s patients

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RoboPets

In dementia cases, the instinct to look after and nurture something or someone can be among the last things to leave a person. People with the neurodegenerative condition may hold dolls while in care, for example, as their brain recognises them as objects requiring their care and attention. 

While pets can also help to satisfy this need, taking care of them may be too much responsibility for many with the disease. A new solution is emerging, however, in the form of robotic animals. 

At the heart of this robot-revolution is Deborah Spratley, founder of Plymouth-based RoboPets, which distributes these devices to care homes across the UK.

The soft and cuddly animals have shown their power to transform dementia and Parkinson’s patients’ quality of life – but are far more than mere toys.  They utilise the latest robotic technology to respond to their carers actions, as well as making life-like noises.

They help to foster a sense of responsibility, and empowerment, allowing patients to forget about their conditions and feel in control of their lives.

Deborah says: “The pets completely change a person’s mood. One of the last things that leaves a person with dementia  is this feeling of nurturing but in their day-to-day lives they can’t do that. They are the ones being taken care of.

“By introducing the pets – and some dementia patients will believe they are real – it empowers them as they think they are taking care of and loving something, where normally they are the vulnerable ones.

“Even I sometimes forget they’re not real because they respond to you, so when you touch and stroke them it’s quite wonderful.

“The response people have from them is great, they’re happy and smiling and some of them just come alive again. I’ve seen this for myself in my local hospital.”

While the technology is largely well received, Deborah has faced an uphill battle in  persuading some professionals of its benefits.

She recalls one occasion when she conducted a trial visit at a local care home, where senior staff were initially unconvinced of the idea.

A resident with dementia, who was often unresponsive, was given one of the robotic cats, and it instantly changed her mood and behaviour.

She was happy and rejuvenated and made such a connection with the pet that Deborah didn’t have the heart to take it away from her.

“In the beginning it was difficult. But because of the word of mouth people now know the huge benefits.

“Loved ones who buy one for their mother or father in a care home can really show everyone the benefits and now I have people from the NHS buying them.”

A number of care facilities and hospitals in the UK and Europe have looked beyond the scepticism to embrace RoboPets as a means of improving their patient’s quality of life.

A sense of companionship and the feeling of being able to understand and love something that isn’t too complicated is what draws many towards pets. And it’s not so different with their robotic counterparts.

They too have helped patients to feel less isolated during the pandemic and brought some comfort to those cut off from their loved ones.

Alongside older users, demand is growing for them in terms of  helping children with special needs and mental health problems, offering a relaxing device which teaches responsibility.

There is also a specific model for children called Purrble – a small fluffy creature designed to help ease anxiety and stress.

Currently RoboPets supplies robotic cats and dogs, however it is soon looking to branch out to other animals with a rabbit in development and a bird set to hit the UK soon.

It is a family run company, with Deborah’s daughter Kerrie helping with operations and her 88-year-old mother having her own robotic pet.

Through its good work the organisation has attracted a lot of media attention, such as starring in a special feature on BBC News which skyrocketed sales.

“They showed one of the care homes in Essex we supply,” Deborah says. “That was where it stemmed from and the demand was just phenomenal, every second people were ordering from us.

“Prior to the pandemic I was going out to care homes and hospitals on a one-woman mission to promote them and doing exhibitions.

“But for that publicity to be there is just tremendous and it’s wonderful that more people are aware of RoboPets.”

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