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(Inglés) Paciente de Parkinson recibe un implante y revierte síntomas

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(Inglés) Paciente de Parkinson recibe un implante y revierte síntomas

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Parkinson’s patient first to receive brain implant that reverses symptoms
Steve Fink, APRIL 27, 2022

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Alan Whone, Consultant Neurologist. holding a model of The Picostim™ DBS system

A British hospital is the first in the world to implant a brain device that reverses the symptoms of Parkinson’s disease. Now, its test patient is gushing over the results and says he’s gotten his life back.

Surgeons at Southmead Hospital in Bristol are implementing a tiny deep brain stimulation (DBS) device into the skull. It overrides the abnormal brain-cell firing patterns caused by Parkinson’s.

Twenty-five Parkinson’s disease patients have been selected for the trial at North Bristol NHS Trust that will finish next year. If the trial is successful, it will be possible to treat more Parkinson’s patients more easily.

The trial’s first patient Tony Howells, who was diagnosed with Parkinson’s nine years ago, said the impact was “amazing.”

“Before the operation I went for a walk on Boxing Day with my wife and I got 200 yards (182m) from the actual car,” he tells South West News Service. “I had to turn around and go back because I just couldn’t walk. Then after the operation, which was 12 months later, I went on Boxing Day again and we went for 2.5 miles (4km) and we could’ve went further. It was amazing.”

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Excelente noticia, pero en el futuro deberán desarrollar mejores soluciones que traten la causa que provoca la degeneración de las células cerebrales.
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Stem cell therapy set for human trials after reversing Parkinson's in rats
By Nick Lavars, May 11, 2022

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An innovative stem cell therapy has demonstrated the potential to replace lost neurons in Parkinson's disease

Stem cell therapies are showing huge promise in a lot of areas, but one application that has scientists particularly excited is in next-generation treatments for Parkinson's disease. A team experimenting in this area has demonstrated how implanting carefully cultivated stem cells into rats can bring about remarkable recovery from motor symptoms typical of the disease, and are now setting their sights on upcoming human trials.

Parkinson's disease is considered a prime target for innovative stem ell therapies because the condition can be traced back to the deterioration of a particular type of cell in a particular region of the brain. The neurons in the substantia nigra, a structure in the midbrain, are responsible for producing dopamine, which helps control movement, among other things.

The loss of these neurons is what contributes to motor symptoms in Parkinson's patients, so using stem cell therapies to replace them is a very appealing idea, and one that has started to migrate from animal testing to humans. In a world-first trial undertaken in Japan in 2018, Parkinson's patients had stem-cell-derived precursor cells implanted into their brains where they matured into the dopamine-producing neurons, with a number of subjects reported to be doing well.

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Brain cells that are linked to Parkinson’s disease finally identified
Clare Wilson, HEALTH 5 May 2022

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An MRI brain scan of a 58-year-old with Parkinson’s disease ZEPHYR/SCIENCE PHOTO LIBRARY

The subtype of brain cells that die in Parkinson’s disease has been discovered using a new technique that can identify which genes are active in individual cells.

We have known for decades that Parkinson’s disease, a progressive condition that results in the development of tremors and difficulties in moving, is linked with the gradual death of cells in part of the brain called the substantia nigra. The cells concerned make a signalling chemical called dopamine, involved in controlling movement – but their exact identity was unclear.

Medicines for Parkinson’s disease boost dopamine in various ways, yet their effects tend to wane over time, so better treatments are needed, says Evan Macosko at the Broad Institute of MIT and Harvard.

Macosko’s team looked at cells from the substantia nigra of eight people who didn’t have Parkinson’s and had agreed to donate their brains for research after death.

The researchers used a relatively new technique called single cell RNA sequencing, which allows cells within a tissue to be analysed individually to see which of their genes are active and producing proteins. They found there were 10 different subtypes of dopamine-producing cells within the substantia nigra.

Next, the researchers used the same technique on the brains of 10 people who had died with either Parkinson’s or a similar condition called Lewy body dementia. They found that only one of the subtypes of brain cells was reduced in number, suggesting many cells of this subtype had died while the people were alive.

There are about 100,000 of these cells in a healthy adult brain. “It’s a very small subset,” says Macosko. “It was like looking for a needle in a haystack.”

The findings should lead to a better understanding of the causes of Parkinson’s and a way to assess potential treatments, he says. If the cells are grown in a dish, new medicines could be tested on them, for instance. Some groups are also trying to develop dopamine-making cells that could be transplanted into the brains of people with Parkinson’s.

Journal reference: Nature Neuroscience, DOI: 10.1038/s41593-022-01061-1

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La única Revolución es la Revolución Moral
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Excelente noticia, antes de terminar este siglo ya esa enfermedad y otras degenerativas serán erradicadas y la esperanza de vida alargada.
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First-of-a-kind blood test paves way for early Parkinson's diagnosis
Nick Lavars, May 26, 2022

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A new test that focuses on biomarkers in blood serum has shown promise as a way of detecting Parkinson's - Depositphotos

With no way of completely curing the condition, earlier diagnosis of Parkinson's disease can have profound impacts on treatment options and a patient's quality of life. Scientists are making inroads when it comes to picking up the tell-tale signs of the disease's onset, and a new first-of-a-kind study has demonstrated how these might be revealed through an inexpensive blood test that has shown a high degree of accuracy in early trials.

Doctors will currently diagnose Parkinson's disease by making an assessment of a patient's motor symptoms, medical history and physical and mental well-being, but symptoms can be hard to distinguish from other neurological conditions. And because early and accurate diagnosis creates a larger window for lifestyle interventions such as exercise and treatment options such as the drug levodopa, which are more effective in its early stages, there is considerable interest in improving on current methods.

Biomarkers that show up in the blood or even skin are seen as highly promising tools that may offer clear and early evidence of the onset of Parkinson's, and scientists are making some exciting inroads in the development of tests designed to detect them. One we looked at back in 2016, for example, focused on detecting abnormal metabolism of blood cells in Parkinson's patients, while another in 2020 showed that sufferers had shorter telomeres, structures at the end of chromosomes, which could be revealed via blood samples.

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En mi opinión las terapias basadas en regenerar la muerte neuronal vía implantes de células madre son un "dead end". Es imposible recapitular en vida adulta la serie de estadios del desarrollo que son imprescindibles para que las células implantadas establezcan las conexiones necesarias dentro de su circuito natural. Es por ello que a la fecha ningún ensayo clínico en humanos basado en estas ha funcionado.

Las aproximaciones basadas en estimulación cerebral vía implantes son ciertamente un buen paliativo. EL problema es que no funcionan en todos los casos. Peor aún, en otros empeoran el cuadro. Hay aspectos idiosincráticos que aún no conocemos en estas enfermedades.
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Scientists zero in on genetic causes of Parkinson's
Bill Hathaway, Yale University, JULY 15, 2022

Variants of at least 20 different genes have been closely linked to the development of Parkinson's disease, but scientists are still investigating how exactly they cause the severe and incurable motor disorder that afflicts about 1 million people in the U.S. alone.

New research by Yale researchers offers important clues. In two new papers, scientists provide insight into the function of a protein called VPS13C, one of the molecular suspects underlying Parkinson's, a disease marked by uncontrollable movements including tremors, stiffness, and loss of balance.

"There are many roads to Rome; likewise there are many roads leading to Parkinson's," said Pietro De Camilli, the John Klingenstein Professor of Neuroscience and professor of cell biology at Yale and investigator for the Howard Hughes Medical Institute. "Laboratories at Yale are making progress toward elucidating some of these paths."

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Modified MRI spies the early signs of Parkinson's disease
By Nick Lavars, July 20, 2022

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A modified MRI technique has shown promise in detecting the early signs of Parkinson's disease

It is thought that Parkinson's disease takes hold in the brain long before obvious motor symptoms appear, and a big focus for researchers is the development of diagnostic tools that can detect it early on. Scientists in Israel have demonstrated a promising new technology in this space, using a variation of MRI to spot tiny, telltale structures forming deep in the brain as the disease progresses.

Led by scientists at the Hebrew University of Jerusalem, the research leverages an imaging technology known as quantitative MRI (qMRI). This adaptation of conventional MRI is able to dig deeper into the chemical structure and composition of tissues by capturing several MRI images at different excitation energies.

The researchers adapted this tool to study a region of the brain known as the striatum, which is known to deteriorate during the progression of Parkinson's disease. By examining the brains of 99 early-stage Parkinson's patients and 46 healthy controls, the scientists were able to spot tiny structural differences in a part of the striatum called the putamen. They were then able to link these abnormalities with the decline in dopamine that is characteristic of the condition, and the loss of motor symptoms that this creates.

"In Parkinson’s disease patients, we found abnormal gradients in the putamen, revealing changes in the posterior putamen that explain patients’ dopaminergic loss and motor dysfunction," the researchers said in their paper.

According to the team, the measurements achieved with the qMRI technique are so sensitive they would only otherwise be possible through examinations of brain cells post mortem. Doing so safely in living patients bodes well for the early diagnosis of Parkinson's and other neurodegenerative diseases, though the team anticipates between three and five years of work is still needed to translate the technology into a clinical tool.

Further to diagnostics, the team believes the technology could also be used to track fine structural changes in the brain as a way of monitoring disease progression. In this way, it could also be used to monitor the efficacy of drugs and open the door to personalized treatments.

"When you don't have measurements, you don't know what is normal and what is abnormal brain structure, and what is changing during the progress of the disease," said study leader Professor Aviv Mezer. "What we have discovered is the tip of the iceberg,"

The research was published in the journal Science Advances.

Source: Hebrew University of Jerusalem via ScienceDaily

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Gut bacteria linked to Parkinson's, paves way for targeted treatment
Paul McClure, May 07, 2023

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A new study has linked a species of gut bacteria to the development of Parkinson's disease / Depositphotos

A new study has found that a species of gut bacteria cause the destructive nerve cell ‘clumps’ that are a hallmark of Parkinson’s disease. The discovery opens the door to the development of targeted treatments for this debilitating disease.

More than 10 million people worldwide live with Parkinson’s disease (PD), an incurable neurodegenerative disorder characterized by tremors, muscle stiffness, hindered movement, and impaired balance and coordination.

When the protein alpha-synuclein (alpha-syn), predominantly found in nerve cells, clumps together, it forms Lewy bodies. The presence of alpha-syn/Lewy bodies in the brain and throughout the nervous system is a hallmark of PD. Clumped alpha-syn has also been found in the gut, and it’s thought that a gut-based pathogen may cause the aggregation, which then travels to the brain.

In an effort to better understand what causes PD, researchers from the University of Helsinki in Finland have closely examined the role that a species of bacteria – Desulfovibrio (DSV) – might play.

They’d looked at the link between DSV and PD in 2021 when they found the bacteria were more prevalent in people with the disease. They also found that, in people with PD, having more of these bacteria correlated with the severity of symptoms seen.

However, in the previous study, the way DSV contributed to the development of PD was not explored. Now, the researchers turned to science’s favorite worm, Caenorhabditis elegans (C. elegans), to examine whether DSV strains contributed to alpha-syn aggregation and PD.

The researchers recruited 20 participants: 10 with PD and 10 healthy individuals. The healthy individuals just happened to be the spouses of the PD participants. Each participant provided fecal samples, which were analyzed for the presence of DSV.

DSV strains found in either group were fed to C. elegans worms whose heads were imaged under a microscope. They also looked at whether the C. elegans’ survival was affected by the bacteria. The researchers fed strains of the bacteria Escherichia coli (E. coli) to worms that acted as a control group.

The researchers found that worms fed DSV bacteria from individuals with PD had significantly more and larger alpha-syn aggregates than worms fed from healthy individuals or worms fed E. coli strains. They also found that the worms who received DSV strains from people with PD died in significantly higher quantities than worms fed E. coli.

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Aggregation of alpha-synuclein (alpha-syn), seen here as the darker matter, in a nerve cellTimo Myöhänen Research Group/University of Helsinki

As a result of their findings, the researchers concluded that DSV strains from people with PD, as opposed to healthy people, appear more toxic and can cause more alpha-syn aggregation. They say the study’s findings point to the important role that environmental factors play in the development of PD.

“Our findings are significant, as the cause of Parkinson’s disease has gone unknown despite attempts to identify it throughout the last two centuries,” said Per Saris, a co-author of the study. “The findings indicate that specific strains of Desulfovibrio bacteria are likely to cause Parkinson’s disease. The disease is primarily caused by environmental factors, that is, environmental exposure to the Desulfovibrio bacterial strains that cause Parkinson’s disease. Only a small share, or roughly 10%, of Parkinson’s disease is caused by individual genes.”

Their findings, they say, suggest that DSV bacteria contribute to the development of PD by causing the aggregation of alpha-syn, opening the door to new treatments that specifically target these bacteria.

“Our findings make it possible to screen for the carriers of these harmful Desulfovibrio bacteria,” Saris said. “Consequently, they can be targeted by measures to remove these strains from the gut, potentially alleviating and slowing the symptoms of patients with Parkinson’s disease.”

Further studies could uncover the differences between the DSV strains seen in people with PD and healthy people, something that couldn’t be done in the current study.

The study was published in the journal Frontiers in Cellular and Infection Microbiology.

Source: University of Helsinki
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Machine learning tool may diagnose Parkinson’s years before symptoms appear
Paul McClure, May 10, 2023

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New research has used a specially-designed machine learning algorithm to identify unique combinations of metabolites that may be able to detect Parkinson’s disease early / Depositphotos

Parkinson’s disease (PD) is growing more rapidly than any other neurological disease, which makes its early detection so important. Researchers have developed a new machine-learning tool that shows promise as a way of detecting the disease early.

A diagnosis of PD usually occurs when a person presents with the traditional symptoms: slowed movements, tremors, poor balance and coordination, and muscular rigidity.

But the onset of atypical symptoms such as fatigue, trouble sleeping, bladder or bowel problems, depression and/or anxiety, and loss of smell can predate traditional PD symptoms by many years. A reliable method of testing for biomarkers that leads to an early diagnosis of PD instead of waiting for the appearance of traditional symptoms would mean that treatment of the disease can begin earlier.

Now, researchers from the University of New South Wales Sydney, in collaboration with Boston University, have harnessed the power of machine learning to develop a tool that shows promise as an early detector of PD.

Machine learning is widely used to develop accurate models for disease prediction. And advanced machine learning methods, like neural networks, are a way of processing large volumes of data. However, to be effective, the machine learning algorithm needs to be taught using data that is not ‘noisy’. Metabolomics, the large-scale study of metabolites, can be problematic in this regard.

Many metabolites – by-products created when the body breaks down food, drugs, and chemicals – are correlated with other metabolites, some of which do not contribute significantly to disease prediction.

That’s why the researchers developed a new machine learning tool, the Classification and Ranking Analysis using Neural network generates Knowledge from Mass Spectrometry or CRANK-MS.

“[T]o figure out which metabolites are more significant for the disease versus control groups, researchers usually look at correlations involving specific molecules,” said J Diana Zhang, lead author of the study. “But here we take into account that metabolites can have associations with other metabolites – which is where machine learning comes in. With hundreds to thousands of metabolites, we’ve used computational power to understand what’s going on.”

The researchers obtained metabolomic data from the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC), focusing on 39 patients who’d developed PD and ran it through CRANK-MS. After comparing PD patients to healthy patients, the researchers were able to identify unique metabolic combinations that could be early warning signs of the disease.

The beauty of using CRANK-MS is that the researchers could use unadulterated data, which simplified the process.

“Typically, researchers using machine learning to examine correlations between metabolites and disease reduce the number of chemical features first, before they feed it into the algorithm,” said William Donald, the study’s corresponding author. “But here we feed all the information into CRANK-MS without any data reduction right at the start. And from that, we can get the model prediction and identify which metabolites are driving the prediction the most, all in one step. It means that if there are metabolites which may potentially have been missed using conventional approaches, we can now pick those up.”

While CRANK-MS was able to analyze metabolites indicative of PD with an accuracy of up to 96%, the researchers understand that the study’s small sample size means that further studies are needed.

The researchers say that, in future, CRANK-MS could be used at the first sign of atypical symptoms to ensure the early diagnosis of PD or to rule it out. And the machine learning algorithm is publicly available for researchers who might want to use it.

“We’ve built the model in such a way that it’s fit for purpose,” Zhang said. “The application of CRANK-MS to detect Parkinson’s disease is just one example of how AI can improve the way we diagnose and monitor disease. What’s exciting is that CRANK-MS can be readily applied to other diseases to identify new biomarkers of interest.”

The study was published in the journal ACS Central Science.

Source: University of NSW Sydney

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